A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice South African hypertension guideline 2011. Antihypertensive medications and C-reactive protein in the multi-ethnic study of atherosclerosis. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study. Effect of different antihypertensive drug classes on central aortic pressure. Choices, persistence and adherence to antihypertensive agents: evidence from RAMQ data. Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients. Effects of antihypertensive agents, alpha receptor blockers, beta blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and calcium channel blockers, on oxidative stress 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS). Long-Term Use of Angiotensin Receptor Blockers and the Risk of Cancer Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Differences in antihypertensive drug persistence associated with drug class and gender: a PHARMO study. Effects of the Oral Direct Renin Inhibitor Aliskiren in Patients With Symptomatic Heart Failure Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE). Renoprotective Effect and Cost-Effectiveness of Using Benidipine, a Calcium Channel Blocker, to Lower the Dose of Angiotensin Receptor Blocker in Hypertensive Patients with Albumiuria Angiotensin II Type 1 Receptor Blockers Reduce Urinary Oxidative Stress Markers in Hypertensive Diabetic Nephropathy Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. Efficacy of Combination Antihypertensive Therapy with Low-Dose Indapamide: Assessment by Blood Pressure Self-Monitoring at Home Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy. Angiotensin II receptor blocker-based therapy in Japanese elderly, high-risk, hypertensive patients. Erythropoietin resistance in patients on continuous ambulatory peritoneal dialysis. Effect of irbesartan monotherapy compared with ACE inhibitors and calcium‐channel blockers on patient compliance in essential hypertension patients: A multicenter, open‐labeled, three‐armed study Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs Angiotensin II receptor blocker prevents increased arterial stiffness in patients with essential hypertension. Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Effects of renin-angiotensin-aldosterone system inhibitors and beta-blockers on markers of arterial stiffness. MADIT-II and its implications. A five-year comparison of the renal protective effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with non-diabetic nephropathy. Effects of olmesartan, an angiotensin II receptor blocker, and amlodipine, a calcium channel blocker, on Cardio-Ankle Vascular Index (CAVI) in type 2 diabetic patients with hypertension. An angiotensin II receptor blocker–calcium channel blocker combination prevents cardiovascular events in elderly high-risk hypertensive patients with chronic kidney disease better than high-dose angiotensin II receptor blockade alone Population-based study of statins, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors on pneumonia-related outcomes. Prevention of cardiovascular events with calcium channel blocker-based combination therapies in patients with hypertension: a randomized controlled trial The effect of valsartan, captopril, or both on atherosclerotic events after acute myocardial infarction: an analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT). Renoprotective Effect of Calcium Channel Blockers in Combination with an Angiotensin Receptor Blocker in Elderly Patients with Hypertension. A Randomized Crossover Trial Between Benidipine and Amlodipine Comparison of the Effects of Quinapril and Losartan on Carotid Artery Intima-Media Thickness in Patients with Mild-to-Moderate Arterial Hypertension Relationship of Antihypertensive Treatment Regimens and Change in Blood Pressure to Risk for Heart Failure in Hypertensive Patients Randomly Assigned to Doxazosin or Chlorthalidone: Further Analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2019 EXECUTIVE SUMMARY. Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study. Reduction of morbidity and mortality by statins, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers in patients with chronic obstructive pulmonary disease. A 16-week, randomized, double-blind, placebo-controlled, crossover trial to quantify the combined effect of an angiotensin-converting enzyme inhibitor and a beta-blocker on blood pressure reduction. Effect of angiotensin receptor blockade on central haemodynamics in essential hypertension: results of a randomised trial Combination therapy for hypertension in the elderly: a sub-analysis of the Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) Trial Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey Design and statistical aspects of the African American Study of Kidney Disease and Hypertension (AASK). Hyperkalemia as a constraint to therapy with combination Renin-Angiotensin system blockade: the elephant in the room. Characteristics of participants at baseline in the Treatment of Mild Hypertension Study (TOMHS). Long-term effects of addition of mineralocorticoid receptor antagonist to angiotensin II receptor blocker in patients with diabetic nephropathy: a randomized clinical trial. The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil. Calcium channel blockers and cardiac mortality in the treatment of hypertension: a report from the Department of Health Hypertension Care Computing Project (DHCCP) Another treatment gap: restarting secondary prevention medications: the Women's Health Initiative. [Efficacy of monotherapy with 15 antihypertensive agents in treating essential hypertension assessed by 24-hour ambulatory blood pressure monitoring]. Combination Therapy of Calcium Channel Blocker and Angiotensin II Receptor Blocker Reduces Augmentation Index in Hypertensive Patients Patterns of antihypertensive medication use in hemodialysis patients. Safety and tolerability of the direct renin inhibitor aliskiren: a pooled analysis of clinical experience in more than 12,000 patients with hypertension. Aldosterone breakthrough during therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in proteinuric patients with immunoglobulin A nephropathy. Rationale, design and patient baseline characteristics of OlmeSartan and calcium antagonists randomized (OSCAR) study: a study comparing the incidence of cardiovascular events between high-dose angiotensin II receptor blocker (ARB) monotherapy and combination therapy of ARB with calcium channel bloc Long‐term effects of patiromer for hyperkalaemia treatment in patients with mild heart failure and diabetic nephropathy on angiotensin‐converting enzymes/angiotensin receptor blockers: results from AMETHYST‐DN Efficacy of ACE inhibitors and ATII receptor blockers in patients with microalbuminuria: a prospective study Brain natriuretic peptide-guided therapy for heart failure Gender disparities in diabetes and coronary heart disease medication among patients with type 2 diabetes: results from the DIANA study The risk of myocardial infarction associated with antihypertensive drug therapies. Renoprotective Effect of the Addition of Losartan to Ongoing Treatment with an Angiotensin Converting Enzyme Inhibitor in Type-2 Diabetic Patients with Nephropathy Associations of anti-hypertensive treatments with Alzheimer's disease, vascular dementia, and other dementias. Long‐term renoprotection by perindopril or nifedipine in non‐hypertensive patients with Type 2 diabetes and microalbuminuria Rationale for the use of combination angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy in heart failure. Analysis of adverse effects among patients with essential hypertension receiving an ACE inhibitor or a beta-blocker. Efficacy of low dose spironolactone in chronic kidney disease with resistant hypertension. A Simplified Approach to the Treatment of Uncomplicated Hypertension: A Cluster Randomized, Controlled Trial Effects of valsartan, an angiotensin II receptor blocker, on coronary atherosclerosis in patients with acute myocardial infarction who receive an angiotensin-converting enzyme inhibitor. Markov modeling analysis of health and economic outcomes of therapy with valsartan versus amlodipine in patients with type 2 diabetes and microalbuminuria. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. Additive antiproteinuric effect of combined ACE inhibition and angiotensin II receptor blockade Protocol of the Long-term Impact of RAS Inhibition on Cardiorenal Outcomes (LIRICO) randomized trial. Age-Related Difference in the Sleep Pressure-Lowering Effect Between an Angiotensin II Receptor Blocker and a Calcium Channel Blocker in Asian Hypertensives: The ACS1 Study Efficacy and safety of the selective aldosterone blocker eplerenone in Japanese patients with hypertension: a randomized, double-blind, placebo-controlled, dose-ranging study. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation. Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis Augmented short- and long-term hemodynamic and hormonal effects of an angiotensin receptor blocker added to angiotensin converting enzyme inhibitor therapy in patients with heart failure. Vasodilator Heart Failure Trial (V-HeFT) Study Group. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): Practical Implications Hypertension and Its Treatment in Postmenopausal Women: Baseline Data from the Women’s Health Initiative Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension–2 Cardiovascular prevention in coronary heart disease patients: guidelines implementation in clinical practice. Effects of azilsartan compared to other angiotensin receptor blockers on left ventricular hypertrophy and the sympathetic nervous system in hemodialysis patients. Treatment of hypertension with enalapril and hydrochlorothiazide or enalapril and atenolol: contrasts in hypotensive interactions. Efficacy of different drug classes used to initiate antihypertensive treatment in black subjects: results of a randomized trial in Johannesburg, South Africa. Antihypertensive efficacy of the angiotensin receptor blocker azilsartan medoxomil compared with the angiotensin-converting enzyme inhibitor ramipril Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity and neurohumoral activation in patients with congestive heart failure. The effects of statins and renin-angiotensin system blockers on atrial fibrillation recurrence following antral pulmonary vein isolation. Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly. Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients Physicians' adherence to guideline-recommended medications in heart failure with reduced ejection fraction: data from the QUALIFY global survey. Differential effects of beta-blockers on albuminuria in patients with type 2 diabetes.
Persistence on treatment affects the efficacy of antihypertensive treatment . We prospect ively investigated the persistence on therapy and the extent of  blood pressure ( BP ) control  in 347 hypertensive patients ( age 59.4 ± 6 years ) r and omly allocated to a first-line treatment with : angiotensin-converting enzyme ( ACE ) inhibitors , calcium-channel blockers ( CCBs ) , ß-blockers , angiotensin-II receptor blockers ( ARBs ) , or diuretics and followed-up for 24-months . Persistence on treatment was higher in patients treated with ARBs ( 68.5 % ) and ACE inhibitors ( 64.5 % ) vs CCBs ( 51.6 % ; p < 0.05 ) , β-blockers ( 44.8 % , p < 0.05 ) , and diuretics ( 34.4 % , p < 0.01 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher persistence in therapy compared with the other molecules used in each therapeutic class . The rate of persistence was significantly higher in patients treated with lercanidipine vs others CCBs ( 59.3 % vs 46.6 % , p < 0.05 ) . Systolic and diastolic BP was decreased more successfully in patients treated with ARBs ( −11.2/−5.8 mmHg ) , ACE inhibitors ( −10.5/−5.1 mmHg ) , and CCBs ( −8.5/−4.6 mmHg ) compared with ß-blockers ( −4.0/−2.3 mmHg p < 0.05 ) and diuretics ( −2.3/−2.1 mmHg , p < 0.05 ) . No ARB , ACE inhibitor , β-blocker , or diuretic was associated with a higher BP control compared with the other molecules used in each therapeutic class . A trend toward a better BP control was observed in response to lercanidipine vs other CCBs ( p = 0.059 ) . The present results confirm the importance of persistence on treatment for the management of hypertension in clinical practice OUTCOMES Extensive data from r and omised controlled trials have shown the benefit of treating hypertension . The target blood pressure ( BP ) for antihypertensive management is systolic < 140 mmHg and diastolic < 90 mmHg with minimal or no drug side-effects ; however , stricter BP control is required for patients with end-organ damage , co-existing risk factors and co-morbidity , e.g. diabetes mellitus . The reduction of BP in the elderly and in those with severe hypertension should be achieved gradually over 1 month . Co-existent risk factors should also be controlled . BENEFITS Benefits of management include reduced risks of stroke , cardiac failure , chronic kidney disease and coronary heart disease . RECOMMENDATIONS The correct BP measurement procedure is described , and evaluation of cardiovascular risk factors and recommendations for antihypertensive therapy are stipulated . The total cardiovascular disease risk profile should be determined for all patients to inform management strategies . Lifestyle modification and patient education are cornerstones in the management of every patient . Major indications , pre caution s and contra-indications to each recommended antihypertensive drug are listed . Combination therapy should be considered ab initio if the BP is ≥ 20/10 mmHg . First-line drug therapy for uncomplicated hypertension includes low-dose thiazide-like diuretics , calcium channel blockers ( CCBs ) or angiotensin-converting enzyme inhibitors ( ACE-Is ) ( or ARBs - angiotensin II receptor blockers ) . If the target BP is not obtained , a second antihypertensive should be added from the aforementioned list . If the target BP is still not met , the third remaining antihypertensive agent should be used . In black patients  either thiazide-like diuretics or CCBs can be used initially , because response rates are better than with ACE-Is or β-blockers . In treating resistant hypertension , a central ly acting drug , vasodilator , α-blocker , spironolactone or β-locker should be added . This guideline includes management of specific situations , i.e. hypertensive emergency and urgency , severe hypertension with target organ damage , hypertension in diabetes mellitus , resistant hypertension , fixed drug combinations , new trials in hypertension , and interactions of antihypertensive agents with other drugs . VALIDITY The guideline was developed by the Southern African Hypertension Society BACKGROUND The effects of different antihypertensive medication classes on C-reactive protein ( CRP ) levels are still not well characterized , and might be of relevance to treatment choices . METHODS We studied the association between antihypertensive medication class and CRP levels among participants with treated hypertension in the Multi-Ethnic Study of Atherosclerosis . We performed a cross-sectional study of hypertensive participants free of clinical cardiovascular disease who were taking one or more of the following medication classes : beta-blockers , calcium channel blockers , diuretics , and angiotensin-converting enzyme ( ACE ) inhibitors , or angiotensin II type I receptor blockers ( ARB ) .  RESULTS Among 2340 participants taking one or more antihypertensive medications , the mean serum CRP level was lower among participants taking a beta-blocker than among those not taking a beta-blocker ( 2.13 v 2.54 mg/L , P = .002 ) . This difference persisted after multivariate adjustment ( P = .021 ) . There were no other statistically significant differences in multivariate models . Among 1314 participants receiving monotherapy , the multivariate adjusted mean CRP level among participants taking a beta-blocker was lower ( 1.97 mg/L ) than those taking a diuretic ( 2.72 mg/L , P < .001 ) . In this monotherapy group , participants taking an ACE inhibitor or ARB also had a lower adjusted mean CRP ( 2.25 mg/L ) than those taking a diuretic ( P = .046 ) . African-American race/ethnicity did not modify any of those relationships . CONCLUSIONS The beta-blocker use was associated with lower CRP levels overall and among participants on monotherapy , whereas ACE inhibitor and ARB use was associated with lower CRP levels among participants on monotherapy . These findings warrant further evaluation in r and omized trials The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually BACKGROUND Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were r and omly allocated to first-line treatment with a calcium channel blocker ( CCB ) , angiotensin-converting enzyme inhibitor ( ACEI ) or angiotensin II receptor blocker ( ARB ) . METHODS We recruited 265 ( 93 for CCB , 71 for ACEI and 101 for ARB ) patients who completed the genomic study .  Home blood pressure was measured for 5 days off-treatment before r and omization and for 5 days after 2 - 4 weeks of r and omized drug treatment . Genotyping was performed by 500 K DNA microarray chips . The blood pressure responses to the three drugs were analyzed separately as a quantitative trait . For replication of SNPs with p < 10(-4 ) , we used the multicenter GEANE study , in which patients were r and omized to valsartan or amlodipine . RESULTS SNPs in PICALM , TANC2 , NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication . CONCLUSION Our approach , the first based on high-fidelity phenotyping by home blood pressure measurement , might be a step in moving towards the personalized treatment of hypertension Central aortic systolic blood pressure ( BP ) is an important determinant of cardiac workload and cardiac hypertrophy . The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels . It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner . In a double-blind crossover study , we measured the effects of the four major drug classes compared with placebo on central aortic pressure . Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus . The study was undertaken in patients aged 65 to 85 years with systolic BP > 150 mm Hg at study entry . Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods .  Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme ( ACE ) inhibitors or beta-blocking drugs . On placebo , central aorta augmentation pressure and index were 23 mm Hg and 33.3 % ; on ACE inhibitors the values were 18 mm Hg and 30 % ; on beta-blockers , 26 mm Hg and 38.5 % ; on calcium channel blockers , 16 mm Hg and 28 % ; and on diuretics , 17 mm Hg and 28.8 % . The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes ( P < .05 ) , and augmentation pressures on ACE inhibitors , calcium channel blockers , and diuretics were less than on placebo ( P < .05 ) . The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics . Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs . The clinical importance of this discrepancy needs to be evaluated BACKGROUND Most treatment recommendations for hypertension are based on criteria that consider efficacy , safety and cost . Given the need for long-term use of antihypertensive agents , treatment compliance should also be taken into consideration in the selection process . OBJECTIVE The purpose of the present study was to estimate persistence and adherence to  antihypertensive agents in a real-life setting . METHODS Persistence and adherence to treatment were estimated using data from the Regie de l'assurance maladie du Quebec . RESULTS Data from a r and om sample of 4561 subjects with a diagnosis of hypertension covered by the Regie de l'assurance maladie du Quebec drug plan and using one of the antihypertensive agents reimbursed by the drug plan for the first time between January 2000 and December 2001 were analyzed . The persistence rate observed after a two-year period with diuretics was significantly lower ( 52.8 % ) than with any other classes of antihypertensive agent ( P<0.01 ) . Persistence rates for beta-blockers , calcium channel blockers , angiotensin-II receptor blockers and angiotensin-I converting enzyme inhibitors were 69.3 % , 64.3 % , 60.9 % and 58.9 % , respectively . After two years , the proportion of patients who were 80 % adherent to their treatment was 64.9 % for angiotensin-I converting enzyme inhibitors , 65.0 % for angiotensin-II receptor blockers , 64.2 % for calcium channel blockers , 60.3 % for beta-blockers and 50.9 % for diuretics . The proportion of patients who were 80 % adherent to their treatment was significantly lower for diuretics than with any other antihypertensive agents ( P<0.01 ) . CONCLUSION Persistence and adherence to treatment are essential to treatment success . Results of the present study indicate that , in a real-life setting , patients are significantly less compliant to diuretics than to any other antihypertensive agents When observed in elderly hypertensive patients , increased pulse pressure ( PP ) and arterial stiffness are known to be independent risk factors for cardiovascular diseases . Increased systolic blood pressure ( SBP ) leads to left ventricular hypertrophy , while decreased diastolic blood pressure ( DBP ) results in decreased coronary circulation . It is known that increased arterial stiffness is the major cause of increased PP . Thus basic morbid states of cardiac failure or ischemic heart diseases are more likely to develop in elderly hypertensive patients with increased PP and arterial stiffness , and there is need of antihypertensive drugs that decrease these effects in elderly hypertensives . In this study , we compared the effects of an angiotensin-receptor blocker ( ARB : valsartan ) , an angiotensin-converting enzyme inhibitor ( ACE-I : temocapril ) , and long-acting Ca antagonists ( L- and N-type Ca channel blocker : cilnidipine ; and L-type Ca channel blocker : nifedipine CR ) on PP and arterial stiffness measured by pulse wave velocity in elderly hypertensive patients for 3 months . The ARB yielded the largest reductions in PP and brachial-ankle pulse wave velocity ( baPWV ) , followed by the ACE-I and L- and N-type Ca channel blocker , while the L-type Ca channel blocker yielded no improvement . The effects on arterial stiffness and PP thus varied among the drug characteristics . Although ARB achieved the largest reduction in baPWV , this decrease was not associated with any reductions in PP , SBP , DBP , or mean blood pressure , as were the baPWV-decreases achieved by the other drugs , suggesting that ARB may further reduce the risk of arteriosclerosis in elderly hypertensive patients by decreasing arterial stiffness in addition to its antihypertensive effect Background Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of hypertension disease ( HD ) . Trace elements function as a co-factor in antioxidant enzymes . The antioxidant system and trace elements have been investigated in many different studies including HD , but these subjects have not been investigated as a whole in these patients . Objective The aim of the present study was to investigate the antioxidative system and trace elements in hypertensive patients given different antihypertensive therapy .  Methods We examined  malondialdehyde and superoxide dismutase activities together with copper and zinc levels in plasma of 102 patients with HD and in 51 healthy controls . Results It was found that in patients with HD , plasma malondialdehyde was significantly higher than those of controls , while plasma superoxide dismutase activities were significantly lower in patients with HD . Plasma zinc levels were significantly higher than those of controls and plasma copper levels were significantly lower in patients with HD . Plasma lipid levels and oxidative state were analyzed in five different treatment groups given antihypertensive drug therapy before and after a 3-month treatment period . Conclusions In conclusion , our clinical study shows that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have notable effects on oxidative stress , and are an essential step in managing essential hypertension by the way of improvement of endothelial dysfunction . Although it has been shown that calcium channel blockers , beta blockers and alpha receptor blockers have antioxidant effects in in vitro conditions , we did not demonstrate these effects in our clinical study Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a  BP goal  of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient A multicenter , r and omized , controlled , double-blind U.S. trial is comparing the combined effects of diet treatment and 1 of 5 active drug regimens with diet treatment alone , for the long-term management of middle-aged adults with " mild " hypertension . Factors stimulating this trial are data documenting the high prevalence of mild hypertension in the adult population ; mild hypertension 's responsibility for a high proportion of morbidity and mortality attributable to hypertension overall ; data from long-term hypertension intervention trials showing reduced morbidity and mortality of people with mild hypertension with use of either diuretics or beta blockers as step-1 therapy , and other trials that failed to demonstrate beneficial impact on morbidity and mortality , possibly due to residual questions concerning aspects of benefit to risk ratios with these medications ; recent data from trials showing long-term control of mild hypertension and other risk factors by nutritional means ; lack of data from long-term trials on benefit to risk ratios with newer drugs such as selective alpha 1 inhibitors , angiotensin converting enzyme inhibitors and calcium channel blockers ; paucity of data from trials on long-term combined effects of diet and drug therapy , and of diet alone , for people with mild hypertension . During the next few years , phase 1 of the trial will study 6 groups of drugs . The step-1 drugs are angiotensin converting enzyme inhibitor ( enalapril ) , alpha 1 inhibitor ( doxazosin ) , beta blocker ( acebutolol ) , calcium channel blocker ( amlodipine ) , diuretic ( chlorthalidone ) and placebo . All participants are to receive vigorous sustained nutritional counseling to reduce obesity , moderate sodium intake and avoid heavy use of alcohol . Key endpoints for phase 1 of the study are the need for additional medication to control mild hypertension , side effects ( i.e. , clinical and biochemical ) and consequent need to discontinue drug and quality of life . Phase-1 data are to be used to complete the phase-2 design , with the ultimate aim to assess effects on morbidity and mortality The association between angiotensin receptor blockers ( ARBs ) and cancer is controversial with meta-analyses of r and omized controlled trials and observational studies reporting conflicting results . Thus , the objective of this study was to determine whether ARBs are associated with an overall increased risk of the four most common cancers , namely , lung , colorectal , breast and prostate cancers , and to explore these effects separately for each cancer type . We conducted a retrospective cohort study using a nested case-control analysis within the United Kingdom ( UK ) General Practice Research Data base . We assembled a cohort of patients prescribed antihypertensive agents between 1995 , the year the first ARB ( losartan ) entered the UK market , and 2008 , with follow-up until December 31 , 2010 . Cases were patients newly-diagnosed with lung , colorectal , breast and prostate cancer during follow-up . We used conditional logistic regression to estimate adjusted rate ratios ( RRs ) and 95 % confidence intervals ( CIs ) of cancer incidence , comparing ever use of ARBs with ever use of diuretics and /or beta-blockers .  The cohort included 1,165,781 patients , during which 41,059 patients were diagnosed with one of the cancers under study ( rate 554/100,000 person-years ) . When compared to diuretics and /or beta-blockers , ever use of ARBs was not associated with an increased rate of cancer overall ( RR : 1.00 ; 95 % CI : 0.96–1.03 ) or with each cancer site separately . The use of angiotensin-converting enzyme inhibitors and calcium channel blockers was associated with an increased rate of lung cancer ( RR : 1.13 ; 95 % CI : 1.06–1.20 and RR : 1.19 ; 95 % CI : 1.12–1.27 , respectively ) . This study provides additional evidence that the use of ARBs does not increase the risk of cancer overall or any of the four major cancer sites . Additional research is needed to further investigate a potentially increased risk of lung cancer with angiotensin-converting enzyme inhibitors and calcium channel blockers BACKGROUND Previous studies have reported an increased risk of cancer with calcium-channel blockers in man . Other work in animals suggests that inhibitors of angiotensin-I-converting enzyme ( ACE ) protect against cancer . We aim ed to assess the risk of cancer in hypertensive patients receiving ACE inhibitors or other antihypertensive drugs .  METHODS Our retrospective cohort study was based on the records of 5207 patients who attended the Glasgow Blood Pressure Clinic between Jan 1 , 1980 , and Dec 31 , 1995 . The patients ' records are linked with the Registrar General Scotl and and the West of Scotl and Cancer Registry . FINDINGS Compared with the West of Scotl and controls , the relative risks of incident and fatal cancer among the 1559 patients receiving ACE inhibitors were 0.72 ( 95 % CI 0.55 - 0.92 ) and 0.65 ( 0.44 - 0.93 ) . Among the 3648 patients receiving antihypertensive drugs other than ACE inhibitors ( calcium-channel blockers 1416 , diuretics 2099 , beta-blockers 2681 ) , the corresponding relative risks were 110 ( 0.97 - 1.22 ) and 1.03 ( 0.87 - 1.20 ) . The relative risk of cancer was lowest in women on ACE inhibitors : 0.63 ( 0.41 - 0.93 ) for incident cancer ; 0.48 ( 0.23 - 0.88 ) for fatal cancer ; and 0.37 ( 0.12 - 0.87 ) for female-specific cancers . The reduced relative risk of cancer in patients on ACE inhibitors was greatest with follow-up of longer than 3 years . Calcium-channel blockers , diuretics , and beta-blockers had no apparent effect on risk of cancer . INTERPRETATION Long-term use of ACE inhibitors may protect against cancer . The status of this finding is more that of hypothesis generation than of hypothesis testing ; r and omised controlled trials are needed OBJECTIVE The objective of the study is to investigate factors related to treatment persistence among users of antihypertensive ( AHT ) drugs in daily practice . METHODS Data for this study were obtained from the PHARMO data base including pharmacy records and hospitalizations in the Netherl and s ( n=950,000 ) . Patients who newly received AHT therapy ( n=17,113 ) between 1997 and 2001 were selected . Of these patients , r and om sample s of 500 patients per drug class were drawn . One-year persistence was defined as ( 1 ) the percentage of patients using AHTs at least 270 days and receiving AHT in 3 months after the 1-year follow-up period , and ( 2 ) Catalan method ( Kaplan-Meier curves ) . Gender specific persistence rates per drug class were adjusted for significant factors including age , use of antidiabetics and lipid lowering drugs , and prior cardiovascular hospitalizations ( OR and 95%CI ) . RESULTS Persistence was highest in users of angiotensin II receptor blockers ( ARBs ) ( 62.0 % ) , progressively lower in users of angiotensin converting enzyme inhibitors ( ACE-inhibitors , 59.7 % ) , betablockers ( 35.0 % ) , calcium channel blockers ( 34.7 % ) , and diuretics ( 33.0 % ) , result ing in the highest OR of 3.4 [ 95%CI : 2.6 - 4.5 ] for ARBs compared to diuretics . The persistence of AHT use in women was substantially lower ( 40.1 % vs. 50.2 % , OR 0.7 [ 95%CI : 0.6 - 0.8 ] ) and differences between drug classes were larger than in men . CONCLUSIONS These results demonstrate marked differences in persistence between AHT classes , with the highest persistence for ARBs and lowest for diuretics . Women were less persistent with their AHT compared to men . This low persistence leads to suboptimal treatment with a potential for substantial clinical consequences . Especially in women , more attention paid to AHT persistence patterns could improve their cardiovascular outcome Background —Loss of negative feedback inhibition of renin release during chronic treatment with an angiotensin-converting enzyme ( ACE ) inhibitor leads to a compensatory rise in renin secretion and downstream components of the renin-angiotensin-aldosterone ( RAAS ) cascade . This may overcome ACE inhibition but should be blocked by a direct renin inhibitor . We studied the effects of adding the direct renin inhibitor aliskiren to an ACE inhibitor in patients with heart failure . Methods and Results — Patients with New York Heart Association class II to IV heart failure , current or past history of hypertension , and plasma brain natriuretic peptide ( BNP ) concentration > 100 pg/mL who had been treated with an ACE inhibitor ( or angiotensin receptor blocker ) and β-blocker were r and omized to 3 months of treatment with placebo  ( n=146 ) or aliskiren 150 mg/d ( n=156 ) . The primary efficacy outcome was the between-treatment difference in N-terminal pro-BNP ( NT-proBNP ) . Patients ’ mean age was 68 years , mean ejection fraction was 31 % , and mean±SD systolic blood pressure was 129±17.4 mm Hg . Sixty-two percent of the patients were in New York Heart Association functional class II , and 33 % were taking an aldosterone antagonist . Plasma NT-proBNP rose by 762±6123 pg/mL with placebo and fell by 244±2025 pg/mL with aliskiren  ( P=0.0106 ) . BNP and urinary ( but not plasma ) aldosterone were also reduced by aliskiren . Clinical ly important differences in blood pressure and biochemistry were not seen between aliskiren and placebo . Conclusions —Addition of aliskiren to an ACE inhibitor ( or angiotensin receptor blocker ) and β-blocker had favorable neurohumoral effects in heart failure and appeared to be well tolerated BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors prevent the expansion and rupture of aortic aneurysms in animals . We investigated the association between ACE inhibitors and rupture in patients with abdominal aortic aneurysms . METHODS We did a population -based case-control study of linked administrative data bases in Ontario , Canada . The sample included consecutive patients older than 65 ( n=15,326 ) admitted to hospital with a primary diagnosis of ruptured or intact abdominal aortic aneurysm between April 1 , 1992 , and April 1 , 2002 . FINDINGS Patients who received ACE inhibitors before admission were significantly less likely to present with ruptured aneurysm ( odds ratio [ OR ] 0.82 , 95 % CI 0.74 - 0.90 ) than those who did not receive ACE inhibitors . Adjustment for demographic characteristics , risk factors for rupture , comorbidities , contraindications to ACE inhibitors , measures of health-care use , and aneurysm screening yielded similar results ( 0.83 , 0.73 - 0.95 ) . Consistent findings were noted in subgroups at high risk of rupture , including patients older than 75 years and those with a history of hypertension . Conversely , such protective associations were not observed for beta blockers ( 1.02 , 0.89 - 1.17 ) , calcium channel blockers ( 1.01 , 0.89 - 1.14 ) , alpha blockers ( 1.15 , 0.86 - 1.54 ) , angiotensin receptor blockers ( 1.24 , 0.71 - 2.18 ) , or thiazide diuretics ( 0.91 , 0.78 - 1.07 ) . INTERPRETATION ACE inhibitors are associated with a reduced risk of ruptured abdominal aortic aneurysm , unlike other antihypertensive agents . R and omised trials of ACE inhibitors for prevention of aortic rupture might be warranted OBJECTIVES Despite a broad and efficient pharmacological antihypertensive armamentarium , blood pressure ( BP ) control is suboptimal and heterogeneous throughout Europe . Recent representative data from Switzerl and are limited . The goal of the present survey was therefore to assess the actual control rate of high BP in Switzerl and in accordance with current guidelines . The influence of risk factors , target organ damage and medication on BP levels and control was also evaluated . METHODS A cross-sectional visit-based survey of ambulatory hypertensive patients was performed in 2009 in Switzerl and . 281 r and omly selected physicians provided data on 5 consecutive hypertensive patients attending their practice s for BP follow-up . Data were anonymously collected on demographics , comorbidities and current medication , and BP was recorded . Subsequent modification of pharmacological antihypertensive therapy was assessed . RESULTS Data from 1376 patients were available . Mean age was 65 ± 12 years , 53.9 % were male subjects . 26.4 % had complicated hypertension . Overall , BP control ( < 140/90 mm Hg for uncomplicated and < 130/80 mm Hg for complicated hypertension ) was achieved in 48.9 % . Compared to patients with complicated hypertension , BP control was better in patients with uncomplicated hypertension ( 59.4 % vs. 19.2 % , p < 0.001 ) . As a monotherapy the most prescribed drug class were angiotensin receptor blockers ( ARB , 41 % ) , followed by angiotensin converting enzyme ( ACE ) inhibitors ( 21.5 % ) , betablockers ( 20.8 % ) and calcium channel blockers ( CCB , 10.8 % ) . The most prescribed drug combinations were ARB + diuretic ( 30.1 % ) and ACE inhibitors + diuretic ( 15.3 % ) . 46 % were receiving a fixed drug combination . In only 32.7 % of patients with uncontrolled hypertension was a change in drug therapy made . CONCLUSION This representative survey on treated adult hypertensive patients shows that , compared to earlier reports , the control rate of hypertension has improved in Switzerl and for uncomplicated but not for complicated , particularly diabetes-associated hypertension . ARBs and ACE inhibitors are the most prescribed antihypertensive drugs for monotherapy , whereas diuretics and ARBs were the most used for combination therapy In hypertensive patients with chronic renal disease ,  angiotensin receptor blockers ( ARBs ) are among the first-line drugs , and calcium channel blockers ( CCBs ) are recommended as a second line . We examined the effects of two therapeutic strategies using ARBs and benidipine , a CCB , on blood pressure ( BP ) , urinary albumin excretion ( UAE ) , and cost-effectiveness in hypertensive patients with albuminuria . Patients whose BP was 140/90 mmHg or higher despite treatment with low- or medium-dose ARBs were assigned r and omly to two groups . In Group A ( n=14 ) , the ARB dose was maximized and then benidipine was added until BP targets were reached ( < 130/85 mmHg ) . In Group B ( n=18 ) , benidipine was administered first and then the ARB dose was increased until BP targets were reached . The BP targets were achieved by ARB alone in 36 % of Group A patients and by the addition of benidipine in 83 % of Group B patients . Finally , BP decreased in each group , reaching the targets in 93 % of Group A patients and 94 % of Group B patients after a 4-month therapeutic period . UAE was decreased in both groups after a 4-month therapeutic period compared to the allocation period ( −33±6 % in Group A , −31±6 % in Group B ; p<0.001 , respectively ) . The monthly drug cost was higher ( 11,426±880 vs. 8,955±410 yen , p=0.012 ) and the cost-effectiveness of antihypertensive treatment was lower ( p=0.003 ) in Group A than in Group B. We conclude that the addition of benidipine to low- or medium-dose ARB is , in light of the renal protection and the cost-effectiveness of this approach , a useful therapeutic strategy for controlling BP in hypertensive patients with albuminuria We tested the hypothesis that blockade of angiotensin II type 1 receptors reduces oxidative stress markers in parallel with urinary albumin and type IV collagen excretions . Sixty-six diabetic patients with nephropathy were r and omly assigned to either the angiotensin II receptor blocker ( ARB ; n=33 ) or trichlormethiazide ( n=33 ) group . The majority of patients had been treated with angiotensin-converting enzyme inhibitors or calcium channel blockers for ≥1 year before the present study . Reduction of blood pressure was not different between the 2 groups , and HbA1c levels did not change over the study period ( 8 weeks ) . Treatment with ARB ( c and esartan 8 mg/day , n=11 or valsartan 80 mg/day , n=22 ) for 8 weeks reduced the levels of plasma monocyte chemoattractant protein 1 , interleukin 6 , urinary 8-epi-prostagl and in F2&agr ; , 8-hydroxydeoxyguanosine , albumin , and type IV collagen , whereas the levels of these markers were not altered with trichlormethiazide ( 2 mg/day ) . Significant correlation was observed between the reduction of the urinary 8-epi- prostagl and in F2&agr ; and 8-hydroxydeoxyguanosine and those of the urinary albumin and type IV collagen . Subjects with large oxidative stress had large reduction rates because of ARB administration and showed large urinary albumin suppression . These results suggest that ARBs  reduce oxidative stress and inflammation in diabetic patients independent of their effects on blood pressure . In addition , increases in oxidative stress caused by angiotensin II may play an important role in the progression of diabetic nephropathy . Our results may help to explain the clinical observation that ARB reduces urinary albumin excretion very efficiently in some patients but not in others BACKGROUND Angiotensin II type 1 receptor blockers have favourable effects on haemodynamic measurements , neurohumoral activity , and left-ventricular remodelling when added to angiotensin-converting-enzyme ( ACE ) inhibitors in patients with chronic heart failure ( CHF ) . We aim ed to find out whether these drugs improve clinical outcome . METHODS Between March , 1999 , and November , 1999 , we enrolled 2548 patients with New York Heart Association functional class II-IV CHF and left-ventricular ejection fraction 40 % or lower , and who were being treated with ACE inhibitors .  We r and omly assigned patients c and esartan ( n=1276 , target dose 32 mg once daily ) or placebo ( n=1272 ) . At baseline , 55 % of patients were also treated with beta blockers and 17 % with spironolactone . The primary outcome of the study was the composite of cardiovascular death or hospital admission for CHF . Analysis was done by intention to treat . FINDINGS The median follow-up was 41 months . 483 ( 38 % ) patients in the c and esartan group and 538 ( 42 % ) in the placebo group experienced the primary outcome ( unadjusted hazard ratio 0.85 [ 95 % CI 0.75 - 0.96 ] , p=0.011 ; covariate adjusted p=0.010 ) . C and esartan reduced each of the components of the primary outcome significantly , as well as the total number of hospital admissions for CHF . The benefits of c and esartan were similar in all predefined subgroups , including patients receiving baseline beta blocker treatment . INTERPRETATION The addition of c and esartan to ACE inhibitor and other treatment leads to a further clinical ly important reduction in relevant cardiovascular events in patients with CHF and reduced left-ventricular ejection fraction BACKGROUND Actions of angiotensin II may contribute to the progression of heart failure despite treatment with currently recommended drugs . We therefore evaluated the long-term effects of the addition of the angiotensin-receptor blocker valsartan to st and ard therapy for heart failure . METHODS A total of 5010 patients with heart failure of New York Heart Association ( NYHA ) class II , III , or IV were r and omly assigned to receive 160 mg of valsartan or placebo twice daily . The primary outcomes were mortality and the combined end point of mortality and morbidity , defined as the incidence of cardiac arrest with resuscitation , hospitalization for heart failure , or receipt of intravenous inotropic or vasodilator therapy for at least four hours . RESULTS Overall mortality was similar in the two groups . The incidence of the combined end point , however , was 13.2 percent lower with valsartan than with placebo ( relative risk , 0.87 ; 97.5 percent confidence interval , 0.77 to 0.97 ; P=0.009 ) , predominantly because of a lower number of patients hospitalized for heart failure ; 455 ( 18.2 percent ) in the placebo group and 346 ( 13.8 percent ) in the valsartan group ( P<0.001 ) . Treatment with valsartan also result ed in significant improvements in NYHA class , ejection fraction , signs and symptoms of heart failure , and quality of life as compared with placebo ( P<0.01 ) . In a post hoc analysis of the combined end point and mortality in subgroups defined according to base-line treatment with angiotensin-converting-enzyme ( ACE ) inhibitors or beta-blockers , valsartan had a favorable effect in patients receiving neither or one of these types of drugs but an adverse effect in patients receiving both types of drugs . CONCLUSIONS Valsartan significantly reduces the combined end point of mortality and morbidity and improves clinical signs and symptoms in patients with heart failure , when added to prescribed therapy . However , the post hoc observation of an adverse effect on mortality and morbidity in the subgroup receiving valsartan , an ACE inhibitor , and a beta-blocker raises concern about the potential safety of this specific combination We examined the effects of the addition of low-dose indapamide to antihypertensive drugs of other classes , as well as its duration of action , using blood pressure ( BP ) self-monitoring at home . Seventy-six patients undergoing monotherapy with a calcium channel blocker ( CCB ) , angiotensin converting-enzyme inhibitor ( ACEI ) , or angiotensin AT1-receptor blocker ( ARB ) , but had an average morning home systolic BP ( SBP ) ≥ 135 mmHg or diastolic BP ( DBP ) ≥ 85 mmHg , were studied .  Indapamide ( 1 mg ) was added to their existing treatment once daily for 4 weeks . The additional hypotensive effects  of indapamide were evaluated by casual and home BPs , and the results were compared among the three groups of subjects classified according to their initial drug treatment classes . The morning/evening ( M/E ) ratio of BP reduction was calculated to assess the duration of the effect . Overall , indapamide significantly ( P < 0.001 ) lowered morning home BP ( 147 ± 12/87 ± 9 mmHg to 135 ± 12/81 ± 9 mmHg ) , evening home BP ( 138 ± 15/79 ± 10 mmHg to 126 ± 12/73 ± 9 mmHg ) , and casual BP ( 145 ± 21/86 ± 14 mmHg to 136 ± 17/81 ± 13 mmHg ) . All groupsshowed significant indapamide-induced home SBP/DBP decreases , whereas only the ACEI and ARB groups , but not the CCB group , showed a home pulse pressure ( PP ) reduction . Evening SBP and PP decreases were significantly greater in the ARB group than in the CCB group . The mean M/E ratio with indapamide was 0.95 for SBP and 0.85 for DBP . Low-dose indapamide used in combination can provide additional anti-hypertensive efficacy lasting for 24 h. The added effect of indapamide may be more prominent on ARBs than on CCBs Combined antihypertensive therapy plays a crucial role in achieving targeted blood pressure reductions and renoprotection . We therefore compared the antihypertensive and antiproteinuric effects of combined therapy with either a calcium channel blocker ( CCB ) plus an angiotensin II receptor blocker ( ARB ) or an angiotensin converting enzyme inhibitor ( ACE-I ) plus an ARB in patients with type 2 diabetes mellitus complicated by overt nephropathy and mild to moderate hypertension . After a 12-week dietary control period , diabetic patients with mildly to moderately impaired renal function were r and omly assigned to either a CCB ( amlodipine 5 mg once daily ) or an ACE-I ( temocapril 2 mg once daily ) for 12 weeks ( monotherapy period ) . Both groups then received add-on therapy with an ARB ( c and esartan 4 mg once daily ) for an additional 12 weeks . During the monotherapy period , blood pressure was decreased equally well in both groups . Daily urinary protein excretion remained unchanged in the CCB-treated group ( control period , 4.0 + /- 1.8 g/day vs. CCB period , 4.1 + /- 1.9 g/day ; ns ; n = 8) , but decreased in the ACE-I-treated group ( control period , 4.3 + /- 1.8 g/day vs. ACE-I period , 3.5 + /- 1.7 g/day ; p < 0.05 ; n = 9 ) . After the combined therapy period , blood pressure was decreased to the same degree in both groups . Although ARB plus CCB significantly reduced urinary protein excretion ( to 3.5 + /- 1.5 g/day ; p < 0.05 vs. control period ; n = 8) , a more profound reduction was achieved with ARB plus ACE-I ( to 2.6 + /- 1.3 g/day ; p < 0.01 vs. control period ; n = 9 ) . Monotherapy with the ACE-I increased the serum potassium concentration , and this elevation was sustained after addition of the ARB . In contrast , the serum potassium concentration was not influenced by monotherapy with the CCB , but was significantly increased after addition of the ARB . A decreased hematocrit was observed in the ARB plus ACE-I group . The present study suggests that combined antihypertensive therapy with either a CCB plus an ARB or an ACE-I plus an ARB exerts an antiproteinuric effect in patients with type 2 diabetic nephropathy with mildly impaired renal function . Although the latter combination had a more profound effect , it was associated with an increased serum potassium concentration and worsening of renal anemia . Thus , the combination of a CCB and an ARB should be the first line antihypertensive therapy in those with overt diabetic nephropathy . The long-term efficacy of these combined antihypertensive therapies will need to be further addressed in a future study BACKGROUND It is unknown whether high-dose angiotensin II receptor blocker therapy or angiotensin II receptor blocker + calcium channel blocker combination therapy is better in elderly hypertensive patients with high cardiovascular risk . The objective of the study was to compare the efficacy of these treatments in elderly , high-risk Japanese hypertensive patients . METHODS The OlmeSartan and Calcium Antagonists R and omized ( OSCAR ) study was a multicenter , prospect i ve , r and omized , open-label , blinded-end point study of 1164 hypertensive patients aged 65 to 84 years with type 2 diabetes or cardiovascular disease . Patients with uncontrolled hypertension during treatment with olmesartan 20 mg/d were r and omly assigned to receive 40 mg/d olmesartan ( high-dose angiotensin II receptor blocker ) or a calcium channel blocker + 20 mg/d olmesartan ( angiotensin II receptor blocker + calcium channel blocker ) . The primary end point was a composite of cardiovascular events and noncardiovascular death . RESULTS During a 3-year follow-up , blood pressure was significantly lower in the angiotensin II receptor blocker + calcium channel blocker group than in the high-dose angiotensin II receptor blocker group . Mean blood pressure at 36 months was 135.0/74.3 mm Hg in the high-dose angiotensin II receptor blocker group and 132.6/72.6 mm Hg in the angiotensin II receptor blocker + calcium channel blocker group . More primary end points occurred in the high-dose angiotensin II receptor blocker group than in the angiotensin II receptor blocker + calcium channel blocker group ( 58 vs 48 events , hazard ratio [ HR ] , 1.31 , 95 % confidence interval , 0.89 - 1.92 ; P=.17 ) . In patients with cardiovascular disease at baseline , more primary events occurred in the high-dose angiotensin II receptor blocker group ( HR , 1.63 , P=.03 ) ; in contrast , fewer events were observed in the subgroup without cardiovascular disease ( HR , 0.52 , P=.14 ) . This treatment-by-subgroup interaction was significant ( P=.02 ) . CONCLUSION The angiotensin II receptor blocker and calcium channel blocker combination lowered blood pressure more than the high-dose angiotensin II receptor blocker and reduced the incidence of primary end points more than the high-dose angiotensin II receptor blocker in patients with cardiovascular disease . The addition of a second antihypertensive agent is more effective at lowering blood pressure than simply doubling the dose of an existing agent Anemia is one of the most serious complications in patients on dialysis .  Erythropoietin improves the anemia . However , erythropoietin resistance is sometimes encountered from causes such as functional iron deficiency , secondary hyperparathyroidism , blood loss , or interaction with other drugs . To clarify the interaction between erythropoietin and the renin-angiotensin system , we studied the maintenance dose of recombinant human erythropoietin ( rHuEPO ) in patients on continuous ambulatory peritoneal dialysis ( CAPD ) with and without angiotensin converting enzyme inhibitor ( ACEIs ) , angiotensin II type I receptor blockers ( ARBs ) , and calcium channel blockers . We divided 36 hypertensive patients on CAPD into three groups -- an ACEI group ( n = 12 ) , an ARB group ( n = 12 ) , and a Ca channel blocker group ( n = 12)-- and then we compared the doses of rHuEPO required to maintain the patients ' hematocrit ( Hct ) above 30 % . In the Ca channel blocker group , the weekly dose of erythropoietin had not changed significantly at the end of the study ( 74 + /- 7 U/kg at the end vs. 76 + /- 8 U/kg at the start ) . The ( oral ) ACEI group needed a significantly higher weekly dose of erythropoietin at the end of the study ( 89 -/+ 9 U/kg at the end vs. 74 -/+ 8 U/kg at the start , p < 0.01 ) . The ( oral ) ARB group also needed a significantly higher weekly dose of erythropoietin at the end of the study ( 82 -/+ 10 U/kg at the end vs. 76 + /- 8 U/kg at the start , p < 0.05 ) . Furthermore , the weekly dose of erythropoietin required in the ACEI group was significantly larger than that required in the ARB group . We conclude that treatment with ACEIs and ARBs induces erythropoietin resistance in patients on CAPD . The inhibitory effect of ARBs on erythropoiesis is less than that of ACEIs Objectives . This multicenter , three‐armed , open‐labeled study investigated patient compliance of patients receiving irbesartan , angiotensin‐converting enzyme ( ACE ) inhibitors or calcium‐channel blockers ( CCB ) for essential hypertension for a 6‐month period . Patients were either newly diagnosed or switched from existing antihypertensive medication due to lack of efficacy or side‐effects . Methods . Patients were started monotherapy with irbesartan ( n = 377 ) , ACE inhibitors ( n = 298 ) or CCB ( n = 308 ) and were reevaluated on 1st , 3rd , and 6th months of the treatment . The primary endpoint was patient compliance , assessed by proportion of patients who had taken their study medication every day . Efficacy was recorded as mean reductions in blood pressure and the proportion of patients whose blood pressure normalized . Tolerability was assessed by reported adverse events . Results . Significantly more patients receiving irbesartan had complied with study medication after 3 and 6 months of treatment than ACE inhibitors or CCB . Significantly fewer patients receiving irbesartan needed to change their antihypertensive medication . All three study treatments exhibited similar efficacy profiles , but irbesartan had significantly less adverse events . Conclusions . This study demonstrated that patient compliance to irbesartan was significantly superior to other study treatments . Irbesartan is therefore a suitable first‐line therapy for essential hypertension in everyday clinical practice CONTEXT Hypertension is a leading cause of end-stage renal disease ( ESRD ) in the United States , with no known treatment to prevent progressive declines leading to ESRD . OBJECTIVE To compare the effects of 2 levels of blood pressure ( BP ) control and 3 antihypertensive drug classes on glomerular filtration rate ( GFR ) decline in hypertension . DESIGN R and omized 3 x 2 factorial trial with enrollment from February 1995 to September 1998 . SETTING AND PARTICIPANTS A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease ( GFR , 20 - 65 mL/min per 1.73 m(2 ) ) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years . INTERVENTIONS Participants were r and omly assigned to 1 of 2 mean arterial pressure goals , 102 to 107 mm Hg ( usual ; n = 554 ) or 92 mm Hg or less ( lower ; n = 540 ) , and to initial treatment with either a beta-blocker ( metoprolol 50 - 200 mg/d ; n = 441 ) , an angiotensin-converting enzyme inhibitor ( ramipril 2.5 - 10 mg/d ; n = 436 ) or a dihydropyridine calcium channel blocker , ( amlodipine 5 - 10 mg/d ; n = 217 ) . Open-label agents were added to achieve the assigned BP goals . MAIN OUTCOME MEASURES Rate of change in GFR ( GFR slope ) ; clinical composite outcome of reduction in GFR by 50 % or more ( or > or = 25 mL/min per 1.73 m2 ) from baseline , ESRD , or death . Three primary treatment comparisons were specified : lower vs usual BP goal ; ramipril vs metoprolol ; and amlodipine vs metoprolol . RESULTS Achieved BP averaged ( SD ) 128/78 ( 12/8 ) mm Hg in the lower BP group and 141/85 ( 12/7 ) mm Hg in the usual BP group . The mean ( SE ) GFR slope from baseline through 4 years did not differ significantly between the lower BP group ( -2.21 [ 0.17 ] mL/min per 1.73 m2 per year ) and the usual BP group ( -1.95 [ 0.17 ] mL/min per 1.73 m2 per year ; P = .24 ) , and the lower BP goal did not significantly reduce the rate of the clinical composite outcome ( risk reduction for lower BP group = 2 % ; 95 % confidence interval [ CI ] , -22 % to 21 % ; P = .85 ) . None of the drug group comparisons showed consistent significant differences in the GFR slope . However , compared with the metoprolol and amlodipine groups , the ramipril group manifested risk reductions in the clinical composite outcome of 22 % ( 95 % CI , 1%-38 % ; P = .04 ) and 38 % ( 95 % CI , 14%-56 % ; P = .004 ) , respectively . There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups . CONCLUSIONS No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal . Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline Objective Hypertension guidelines recommend initial treatment with a β-blocker or diuretic and adding the other drug where blood pressure is not controlled . We hypothesized that systematic rotation through the major classes of antihypertensive drugs would demonstrate substantial differences in the pattern of an individual patient 's response , and suggest a more rational approach to choosing best treatment . Design Thirty-four young hypertensives ( age 28–55 , median 47 ) rotated in a double-blind , Latin-square , crossover fashion through 6 weeks of treatment each with amlodipine , doxazosin , lisinopril , bisoprolol , bendrofluazide and placebo . Blood pressure was measured at each visit . ‘ Best ’ drug , defined by efficacy and tolerability , was repeated at the end . Results Rotation doubled the number of patients reaching target blood pressure ( systolic < 140 mmHg ) on one drug ( P = 0.03 ) . All five drugs were represented among the ‘ best ’ drugs . In six patients , the blood pressure on ‘ best ’ drug was at least 10 mmHg lower than on any other . Response to the ‘ best ’ drug was highly correlated ( r = 0.79 ) with its previous administration . By contrast , there were only weak correlations between responses to pairs of drugs , except for angiotensin-converting enzyme ( ACE ) inhibitor ( A ) with β-blocker ( B ) , and calcium blocker ( C ) with diuretic ( D ) – each r = 0.71 , P < 0.005 ) . In these young patients , the majority of patients ( 23/34 ) responded best to a drug suppressing the renin system ( A and B ) . Conclusions Patients vary reproducibly in their response to initial treatment , and switching among drugs can increase the efficacy of monotherapy . The results support an AB/CD scheme for choosing therapy , in which the first drug is taken from one of these pairs , and uncontrolled patients switch to one of the other pair BACKGROUND High pulse wave velocity ( PWV ) is related to cardiovascular risk in essential hypertension ( EHT ) . It is reported that short-term treatment with an angiotensin II receptor blocker ( ARB ) decreases PWV , as well as blood pressure ( BP ) , and increases the serum adiponectin , known as an adipocytokine , which has an anti-atherosclerotic effect . However , it is not known whether long-term treatment with ARB prevents the increase in PWV independently of the reduction of BP , and whether adiponectin is related to the chronic effect of ARB on PWV . METHODS AND RESULTS In order to examine the short-term effect of ARB on PWV , 9 subjects with EHT had PWV measured before and after treatment with an ARB for 1 month . The treatment significantly reduced PWV and BP . For evaluation of the long-term effect of ARB therapy , 56 consecutive subjects with EHT who were already taking anti-hypertensive drugs other than an angiotensin-converting enzyme inhibitor had their PWV measured . We divided the EHT subjects into 2 groups : ( 1 ) the  ARB group ( EHT treated with an ARB for at least 6 months )  and ( 2 ) the control group ( EHT treated with anti-hypertensive drugs other than an ARB )  . Although there was no significant difference between the 2 groups in BP , age or body mass index , the PWV value in the ARB group was significantly lower than that in the control group . Moreover , the serum adiponectin concentration in the ARB group was significantly higher than that in the control group . CONCLUSIONS Long-term treatment with ARB inhibits the progression of arterial stiffness independent of BP reduction . One of the mechanisms may be related to the increased serum adiponectin concentration after treatment with an ARB Abstract Objective : To compare the effectiveness and tolerability of hydrochlorothiazide , atenolol , nitrendipine , and enalapril in patients with mild to moderate hypertension . Design : R and omised multicentre trial over 48 weeks with double blind comparison of treatments . Setting : 48 centres in four countries . Patients : 868 patients with essential hypertension ( diastolic blood pressure 95 - 120 mm Hg ) Interventions : Initial treatment ( step 1 ) consisted of 12.5 mg hydrochlorothiazide ( n=215 ) , 25 mg atenolol ( n=215 ) , 10 mg nitrendipine ( n=218 ) , or 5 mg enalapril ( n=220 ) once daily . If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks , doses were increased to 25 mg , 50 mg , 20 mg , 10 mg , respectively , once daily ( step 2 ) and after two more weeks to twice daily ( step 3 ) . The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure . Main outcome measure : Blood pressure by means of an automatic device with repeated measurements . Results : After eight weeks the response rate for  atenolol  ( 63.7 % ) was significantly higher than for enalapril ( 50.0 % ) , hydrochlorothiazide ( 44.7 % ) , or nitrendipine ( 44.5 % ) . After one year atenolol was still more effective ( 48.0 % ) than hydrochlorothiazide ( 35.4 % ) and nitrendipine ( 32.9 % ) , but not significantly better than enalapril ( 42.7 % ) . The treatment related dropout rate was higher ( P<0.001 ) in the nitrendipine group ( n=28 ) . Conclusions : There is no evidence of superiority for antihypertensive effectiveness or tolerability of the “ new ” classes of antihypertensives ( calcium channel blockers and angiotensin converting enzyme inhibitors ) . As these drugs are now widely used as treatment of first choice , our results further emphasise the need for studies confirming that they also reduce morbidity and mortality , as has been shown for diuretics and ß blockers . Key messages Calcium channel blockers and angiotensin converting enzyme inhibitors as initial monotherapy in the treatment of hypertension Reduction in mortality has been shown only with established ß blockers and diuretics Comparison of treatment with hydrochlorothiazide , atenolol , nitrendipine , and enalapril showed no superiority of the new drug classes Atenolol was the most effective drug , while nitrendipine showed the highest drop out rat  Elderly patients  respond better to hydrochlorothiazide and nitrendipine , and women better to enalapril , although in both subgroups the highest rate of response was with To achieve the target blood pressure recommended by the latest guidelines , multiple antihypertensive drugs are needed in most patients . In this study , the efficacy of treatment using an angiotensin II receptor antagonist ( ARB ) combined with a calcium channel blocker ( CCB ) or a diuretic was compared from multiple perspectives in patients with hypertension . Twenty-nine patients with essential hypertension , who had failed to achieve their target blood pressure ( < 130/85 mm Hg for patients < 65 years old and < 140/90 mm Hg for those ⩾65 years ) when treated with the ARB olmesartan at 20 mg day−1 , were additionally given 8–16 mg day−1 of the CCB azelnidipine or 1–2 mg day−1 of trichlormethiazide ( a thiazide diuretic ) in a r and omized crossover manner for 4 months each . At the end of each combination therapy period , blood and urine sample s were collected and arterial stiffness was evaluated by measuring the cardio-ankle pulse wave velocity . Compared with monotherapy , the blood pressure was reduced similarly by adding azelnidipine ( −12/−10 mm Hg ) or trichlormethiazide ( −14/−9 mm Hg ) . The heart rate was decreased with the CCB by 4 b.p.m . ( P<0.05 ) , whereas it was unchanged with the thiazide . Serum K , lipids and blood glucose were not significantly changed with either combination , whereas serum uric acid was increased with the thiazide ( P<0.01 ) but was unchanged with azelnidipine  . Plasma levels of renin , angiotensin II and aldosterone were also increased with the thiazide period , whereas high-sensitivity C-reactive protein and oxidized low-density lipoprotein were decreased with azelnidipine . In addition , the cardio-ankle vascular index , a parameter of arterial stiffness , was decreased with the azelnidipine period but was unchanged with the thiazide period ( P<0.01 ) . It is suggested that the combination of olmesartan and azelnidipine has advantages over the combination of olmesartan and a thiazide with respect to avoiding hyperuricemia , sympathetic activation , renin – angiotensin-aldosterone system stimulation , inflammation , oxidative stress , and increased arterial stiffness in patients with moderate hypertension . These properties may provide cardiovascular protection in addition to the hypotensive effect BACKGROUND The use of angiotensin-converting enzyme ( ACE ) inhibitors has been linked to a decreased risk of developing cancer , and longer-term use of calcium channel blockers ( CCBs ) has been associated with an increased risk of developing cancer in general and breast cancer in particular . METHODS Using data from the General Practice Research Data base , we conducted a large case-control analysis . Previous exposure to ACE inhibitors , CCBs , and beta-blockers was compared between 3706 postmenopausal women who were diagnosed with incident breast cancer between 1992 and 1997 and 14155 matched-control women . RESULTS Compared with nonusers of antihypertensive drugs , women who used ACE inhibitors ( odds ratio [ OR ] , 1.0 ; 95 % confidence interval [ CI ] , 0.7 - 1.5 ) , CCBs ( OR , 0.9 ; 95 % CI , 0.7 - 1.2 ) , or beta-blockers ( OR , 1.0 ; 95 % CI , 0.8 - 1.2 ) for 5 or more years were not at an increased or decreased risk of developing breast cancer ( adjusted for smoking and body mass index [ calculated as weight in kilograms divided by the square of height in meters ] ) . The risk of breast cancer did not differ between users of different ACE inhibitors or different CCBs ( dihydropyridines , diltiazem hydrochloride , and verapamil hydrochloride ) or between users of short-acting ( OR , 1.0 ; 95 % CI , 0.7 - 1.4 ) or sustained-release ( OR , 1.0 ; 95 % CI , 0.8 - 1.3 ) nifedipine preparations . CONCLUSION The findings of this large case-control analysis do not support the hypothesis that longer-term use of ACE inhibitors or CCBs affects the risk of developing breast cancer Antihypertensive agents may , even within the same class , exert variable effects on arterial stiffness variables .  Nebivolol could have a better impact than atenolol on arterial stiffness , by increasing the bioavailability of endothelium-derived nitric oxide . Angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin receptor blockers ( ARBs ) increase plasma renin activity ( enhancing the production of angiotensin II via non-ACE-related pathways ) whereas aliskiren does not , potentially affecting central hemodynamics differently . We compared the effects of two renin-angiotensin-aldosterone system ( RAAS ) inhibitors ( quinapril and aliskiren ) and 2 beta-blockers ( atenolol and nebivolol ) on arterial stiffness variables . Treatment-naïve patients ( n = 72 ; 68.1 % males ; age , 47.6 ± 10.6 years ) with uncomplicated stage I-II essential hypertension were r and omly assigned to quinapril , aliskiren , atenolol , or nebivolol for 10 weeks . Central systolic and diastolic blood pressure ( BP ) , central pulse pressure ( PP ) , augmentation index ( AIx ) , and pulse wave velocity ( PWV ) were measured at baseline , 2 , and 10 weeks . The same measurements were performed in 20 normotensive subjects ( 65.0 % males ; age , 40.0 ± 8.9 years ) . Peripheral and central systolic and diastolic BP , peripheral PP , and PWV were significantly and similarly reduced by all agents . However , PWV continued to decline between the second and last visit in patients on quinapril and aliskiren but did not change in those on nebivolol or atenolol  . Central PP and AIx decreased in patients on quinapril , aliskiren , and nebivolol but did not change in those taking atenolol . The decrease in central PP and AIx did not differ between patients on quinapril , aliskiren , and nebivolol . Despite similar reductions in peripheral BP , atenolol is less effective than nebivolol and RAAS inhibitors in improving central pulsatile hemodynamics . Aliskiren exerts similar effects on markers of arterial stiffness  as quinapril . The clinical relevance of these differences remains to be established The major risks associated with coronary disease are angina , acute myocardial infa rct ion , reduced cardiac function as manifest by depressed left ventricular ejection fraction and congestive heartfailure , and sudden arrhythmogenic cardiac death . During the past three decades , considerableadvances have been made in the management of patients with coronary heart disease with beta-blockers , calcium-channel blockers , angiotensin converting-enzyme ( ACE ) inhibitors , angiotensin receptor blockers , thrombolytics , balloon-stentangioplasty , and coronary artery bypass graftsurgery .  The clinical course of patients with coronary disease has been meaningfully improved by these therapies , but sudden cardiac death remains a major problem and has not been impacted by these therapeutic interventions . Recently , the Center for Disease Control reported that more than 460 000 sudden cardiac deaths occur annually in the U.S. , with sudden cardiac death accounting for 63 % of all cardiac mortality events.1 Following the introduction of the implanteddefibrillator in 1980 , the defibrillator was initially utilized as secondary prevention for patients with aborted cardiac arrest or documented life-threatening ventricular tachycardia . In 1991 , the Cardiac Arrhythmia Suppression Trial (CAST)investigators reported the ineffectiveness and actual harm associated with several promisingantiarrhythmic drugs that were being used toimprove survival in cardiac patients with manifest ventricular arrhythmias.2 That same year , ourMulticenter Automatic Defibrillator Implantation Trial ( MADIT ) research group initiated the firstr and omized trial to determine if an implantedcardioverter defibrillator ( ICD ) would save lives in coronary patients with prior myocardial infa rct ion , reduced ejection fraction , non-sustained ventricular OBJECTIVE Evidence suggests that the effectiveness of angiotensin-converting enzyme ( ACE ) inhibition diminishes with time , result ing in increasing angiotensin II levels , the action of which can be inhibited by the addition of an angiotensin receptor blocker ( ARB ) . In the present study , the renal protective effects of ACE inhibitors and ARBs were compared over a five-year period in a prospect i ve , r and omized , open-blind study in 68 nondiabetic Japanese patients with elevated serum creatinine levels . PATIENTS AND METHODS Japanese patients with renal insufficiency were r and omly assigned to receive either an  ACE inhibitor ( benazepril 1.25 to 5 mg daily or tr and olapril 0.5 to 4 mg daily ) or ARB ( c and esartan 2 to 8 mg daily or losartan 25 to 100 mg daily )  at the Kidney Disease Center at Saitama Medical School Hospital . The primary study endpoint was a change in glomerular filtration rate ( GFR ) between the baseline value and the last available value obtained during the five-year treatment period , as estimated by the Cockcraft-Gault equation . Secondary endpoints included the annual changes in GFR , serum creatinine level , urinary protein excretion , and blood pressure , as well as the rate of development of endstage renal disease . RESULTS There were no significant differences in the primary endpoint between the two groups . However , after 4 years , the decline in GFR in patients treated with ARBs was significantly greater than that seen in patients treated with an ACE inhibitor ( p<0.05 ) . Furthermore , the rate of introduction of dialysis therapy was also significantly greater in the ARB-treated patients ( 52.7 % in ACE inhibitor and 81.2 % in ARB group at year 5 . p<0.01 ) . CONCLUSION While our data suggested that ARB , like ACE , treatment might slow the progression of renal dysfunction , it also pointed to the necessity to be alerted to the progression to endstage renal disease with longterm medication AIM Recently , a novel device for measuring the cardio-ankle vascular index ( CAVI ) as an arterial stiffness parameter has been developed . In this study , we evaluated the effect of angiotensin II receptor blocker ( ARB ) and calcium channel ( Ca ) blocker on CAVI in type 2 diabetic patients with hypertension . METHODS Seventy type 2 diabetes mellitus patients with hypertension were enrolled and r and omly divided into two groups . One group was administered olmesartan medoxomil 20 mg/day [ DOSAGE ERROR CORRECTED ] for 12 months ( ARB group ) , and the other group was administered amlodipine besilate 5 mg/day for 12 months ( Ca blocker group ) . RESULTS In the ARB group , a significant decrease in CAVI was observed after 12 months ; however , no significant change in CAVI was observed in the Ca blocker group although changes in blood pressure were almost the same . By simple regression analyses , CAVI changes correlated positively with 8-OHdG changes . CONCLUSIONS Olmesartan , an ARB , improved arterial stiffness more than amlodipine , and this effect might be due to not only the blood pressure-lowering effect but also to reducing the potential of oxidative stress recognized in olmesartan The OSCAR study was a multicenter , prospect i ve r and omized open-label blinded end-point study of 1164 Japanese elderly hypertensive patients comparing the efficacy of angiotensin II receptor blocker ( ARB ) uptitration to an ARB plus calcium channel blocker ( CCB ) combination . In this prospect i ve study , we performed prespecified subgroup analysis according to baseline estimated glomerular filtration rate ( eGFR ) with chronic kidney disease ( CKD ) defined as an eGFR < 60 ml/min per 1.73 m2 .  Blood pressure was lower in the combined therapy than in the high-dose ARB cohort in both groups with and without CKD . In patients with CKD , significantly more primary events ( a composite of cardiovascular events and noncardiovascular death ) occurred in the high-dose ARB group than in the combination group ( 30 vs. 16 , respectively , hazard ratio 2.25 ) . Significantly more cerebrovascular and more heart failure events occurred in the high-dose ARB group than in the combination group . In patients without CKD , however , the incidence of primary events was similar between the two treatments . The treatment-by-subgroup interaction was significant . Allocation to the high-dose ARB was a significant independent prognostic factor for primary events in patients with CKD . Thus , the ARB plus CCB combination conferred greater benefit in prevention of cardiovascular events in patients with CKD compared with high-dose ARB alone . Our findings provide new insight into the antihypertensive strategy for elderly hypertensive patients with CKD BACKGROUND Studies suggest that statins and angiotensin-converting enzyme ( ACE ) inhibitors might be beneficial for the treatment of infections . Our purpose was to examine the association of statin , ACE inhibitor , and angiotensin II receptor blocker ( ARB ) use with  pneumonia-related outcomes . METHODS We conducted a retrospective cohort study using Department of Veterans Affairs data of patients aged ≥ 65 years hospitalized with pneumonia . We performed propensity-score matching for 3 medication classes simultaneously . RESULTS Of 50119 potentially eligible patients , we matched 11498 cases with 11498 controls . Mortality at 30 days was 13 % ; 34 % used statins , 30 % ACE inhibitors , and 4 % ARBs . In adjusted models , prior statin use was associated with decreased mortality ( odds ratio [ OR ] , 0.74 ; 95 % confidence interval [ CI ] , .68-.82 ) and mechanical ventilation ( OR , 0.81 ; 95 % CI , .70-.94 ) , and inpatient use with decreased mortality ( OR , 0.68 ; 95 % CI , .59-.78 ) and mechanical ventilation ( OR , 0.68 ; 95 % CI , .60-.90 ) . Prior ( OR , 0.88 ; 95 % CI , .80-.97 ) and inpatient ( OR , 0.58 ; 95 % CI , .48-.69 ) ACE inhibitor use was associated with decreased mortality . Prior ( OR , 0.73 ; 95 % CI , .58-.92 ) and inpatient ARB use ( OR , 0.47 ; 95 % CI , .30-.72 ) was only associated with decreased mortality . Use of all 3 medications was associated with reduced length of stay . CONCLUSIONS Statins , and to a lesser extent ACE inhibitors and ARBs , are associated with improved pneumonia-related outcomes . Prospect i ve cohort and r and omized controlled trials are needed to examine potential mechanisms of action and whether acute initiation at the time of presentation with these infections is beneficial Objectives Current guidelines recommend the use of multiple medications for hypertension . The present study was aim ed at determining which combination was optimal to prevent cardiovascular events . Methods We conducted a prospect i ve , r and omized , open-label , blinded-endpoint trial . Hypertensive out patients aged between 40 and 85 years who did not achieve target blood pressure ( BP<140/90 mmHg ) with calcium channel blocker ( CCB ) benidipine 4 mg/day were r and omly assigned to receive angiotensin receptor blocker ( ARB ) , & bgr;-blocker , or thiazide diuretic in addition to benidipine . Results Among a total of 3501 patients ( 1167 , benidipine-ARB ; 1166 , benidipine-&bgr;-blocker ; and 1168 , benidipine-thiazide ) , 3293 patients ( 1110 , 1089 , and 1094 , respectively ) who received each combination treatment were included in the analysis . Median follow-up was 3.61 years . At the end of the treatment , 64.1 , 66.9 , and 66.0 % of patients in the benidipine-ARB , benidipine-&bgr;-blocker , and benidipine-thiazide groups achieved target BP , respectively . The cardiovascular composite endpoint occurred in 41 ( 3.7 % ) , 48 ( 4.4 % ) , and 32 ( 2.9 % ) patients , respectively : the hazard ratio was 1.26 in the benidipine-ARB ( P = 0.3505 ) and 1.54 in the benidipine-&bgr;-blocker ( P = 0.0567 ) groups compared with the benidipine-thiazide group . The secondary analyses revealed that benidipine and thiazide diuretic significantly reduced the incidence of fatal or nonfatal strokes ( P = 0.0109 ) and benidipine and ARB significantly reduced new-onset diabetes ( P = 0.0240 ) compared with benidipine and & bgr;-blocker . All trial treatments were safe and well tolerated . Conclusion CCB combined with ARB , & bgr;-blocker , or thiazide diuretic was similarly effective for the prevention of cardiovascular events and the achievement of target BP OBJECTIVES We attempted to compare the effect of an angiotensin-converting enzyme ( ACE ) inhibitor and angiotensin receptor blocker ( ARB ) on  atherosclerotic events . BACKGROUND Angiotensin-converting enzyme inhibitors and ARBs interrupt the renin-angiotensin system by distinct mechanisms . It is not clear whether ARBs reduce atherosclerotic events such as myocardial infa rct ion ( MI ) like ACE inhibitors . This evidence gap may reflect the nature of the studies conducted , to date . Placebo-controlled studies enrolled cohorts at low risk of atherosclerotic events ( e.g. , patients with chronic heart failure , most treated with an ACE inhibitor ) . One of the main active controlled trials was confounded by a blood pressure difference between treatments . METHODS We compared the effects of captopril , valsartan , and their combination on atherosclerotic events in 14,703 patients r and omized in the Valsartan in Acute Myocardial Infa rct ion Trial ( VALIANT ) . RESULTS The number of individuals adjudicated as having a fatal or non-fatal MI in the captopril group was 559 ( total investigator reported events 798 ) , 587 ( 796 ) in the valsartan group , and 554 ( 756 ) in the combination group ; valsartan versus captopril , p = 0.651 ( 0.965 ) ; combination versus captopril , p = 0.187 ( 0.350 ) . Overall , all atherosclerotic events examined occurred at a similar frequency in the captopril and valsartan groups . CONCLUSIONS Angiotensin receptor blockers appear to be as effective as ACE inhibitors in reducing atherosclerotic events , even when used in addition to other secondary preventive treatments . These data , although not conclusive , also support the hypothesis that adding an ARB to an ACE inhibitor may have a small additional anti-infa rct ion effect , a possibility that needs to be prospect ively tested Anti-hypertensive medication with an angiotensin II receptor blocker ( ARB ) is effective in slowing the progression of chronic kidney disease . The present study was design ed to investigate whether calcium channel blockers ( CCBs ) in combination with an ARB differentially affect kidney function . Elderly hypertensive patients with chronic kidney disease ( n = 17 , 72 ± 6 years old ) were instructed to self-measure blood pressure . They were r and omly assigned to receive either benidipine ( 4–8 mg/day ) or amlodipine ( 5–10 mg/day ) combined with olmesartan ( 10 mg/day ) . After 3 months , CCBs were switched in each patient and the same protocol was applied for another 3 months . At baseline , significant correlation was obtained between urine albumin ( 22.8 ± 16.7 ( median ± median absolute deviation ) mg/g creatinine ) and self-measured blood pressure ( 170 ± 23/87 ± 10 ( mean ± SD ) mmHg , r = 0.65 , p < 0.01 ) . Both regimens reduced blood pressure to a similar extent ( 139 ± 22/75 ± 11 mmHg and 133 ± 17/72 ± 10 mmHg , respectively ; both p < 0.001 ) , while urine albumin decreased only after combination therapy including benidipine ( 11.7 ± 6.1 mg/g creatinine , p < 0.05 ) . Benidipine , but not amlodipine , in combination with olmesartan , reduced urinary albumin excretion in elderly hypertensive patients with chronic kidney disease . The results suggest the importance of selecting medications used in combination with ARB in hypertensive patients with chronic kidney disease Background : Ultrasonographic evidence of increased carotid intima-media thickness ( IMT ) is known to be associated with generalized atherosclerosis . Therapeutic blockade of the renin-angiotensin system ( RAS ) with angiotensin-converting enzyme ( ACE ) inhibitors reportedly reduces carotid IMT in humans . However , there has been no head-to-head comparison of the effects of ACE inhibitor and angiotensin receptor blocker ( ARB ) , a newer type of RAS inhibitor , on carotid IMT . Methods : 57 hypertensive patients were r and omly assigned to treatment with one of two antihypertensive drugs : ACE inhibitor ( quinapril ; n = 25 , group Q ) or ARB ( losartan ; n = 18 , group L ) . Results : After 1 year of treatment , a similar decrease in mean blood pressure was observed in all groups . Carotid IMT was decreased significantly in group Q ( 10 % decrease , p < 0.05 ) but did not change in group L. There were no significant changes in other atherosclerotic factors between these two groups . Conclusion : Our findings suggest that the antiatherosclerotic effect of quinapril is more potent than that of losartan in hypertensive patients . This effect appears unrelated to the drug ’s antihypertensive action or to traditional atherosclerotic factors Context Previously published results of this r and omized , double-blind trial showed that hypertensive patients treated with doxazosin rather than chlorthalidone more often developed heart failure . Did differences in blood pressure control or treatment with other drugs explain these findings ? Contribution This analysis shows that the slightly worse blood pressure control achieved with doxazosin did not explain higher risks for heart failure . Risks with doxazosin versus chlorthalidone were highest among patients who received monotherapy ( relative risk , 3.10 ) and lowest among patients who received stepped care with additional drugs ( relative risk , 1.42 ) . Implication s Increased risks for heart failure with doxazosin versus chlorthalidone are attenuated but not eliminated when additional antihypertensive drugs are used . The Editors The Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial ( ALLHAT ) , a r and omized , double-blind , multicenter clinical trial including 42 418 participants at 623 clinical sites , is design ed to determine whether treatment begun with a calcium-channel blocker ( amlodipine ) , an angiotensin-converting enzyme inhibitor ( lisinopril ) , or an -adrenergic blocker ( doxazosin ) compared to treatment with a diuretic ( chlorthalidone ) reduces the incidence of fatal coronary heart disease or nonfatal myocardial infa rct ion in high-risk patients with hypertension ( 1 ) . Secondary end points are all-cause mortality , stroke , and other cardiovascular events . A lipid-lowering trial in a subset of 10 356 participants is design ed to determine whether decreasing cholesterol levels with a hydroxymethyl glutamyl coenzyme A reductase inhibitor ( pravastatin ) compared with usual care reduces all-cause mortality in older , moderately hypercholesterolemic patients . In January 2000 , the doxazosin arm of the trial was discontinued ( 2 ) because major cardiovascular disease ( relative risk , 1.25 [ 95 % CI , 1.17 to 1.33 ] ; P < 0.001 ) , especially heart failure ( relative risk , 2.04 [ 95 % CI , 1.79 to 2.32 ] ; P < 0.001 ) , was significantly increased compared with the chlorthalidone arm . Equally important , a low probability existed that doxazosin would show benefit over chlorthalidone for the primary end point by the scheduled study end , given the lack of difference ( relative risk , 1.02 [ 95 % CI , 0.90 to 1.17 ] ; P > 0.2 ] at that time . These intention-to-treat analyses compared patients assigned to chlorthalidone with patients assigned to doxazosin . In this article , we analyze how treatment changes may have affected the comparison of doxazosin with chlorthalidone in terms of heart failure . Our major objectives are to ascertain to what extent the relative risk with doxazosin versus chlorthalidone depends on 1 ) whether the assigned drugs were used as monotherapy or in combination with other agents and 2 ) the difference in decreases in systolic and diastolic blood pressure . Methods Study Design The rationale and design of ALLHAT are described in detail elsewhere ( 1 ) . In brief , eligible participants were men and women 55 years of age or older who had systolic or diastolic hypertension ( 140/90 mm Hg or hypertension controlled with medication ) plus at least one additional risk factor for coronary heart disease events . The risk factors included previous ( > 6 months ) myocardial infa rct ion or stroke , left ventricular hypertrophy on electrocardiography or echocardiography , history of type 2 diabetes , current cigarette smoking , and a low high-density lipoprotein cholesterol level . Persons with a history of hospitalized or treated symptomatic heart failure or a known ejection fraction less than 0.35 were excluded . Unless the drug regimen required tapering for safety , participants who had been taking antihypertensive medications continued to do so until the day of r and omization , at which point they stopped taking all previous medications . On the day after r and omization , treatment with the study drug was initiated . Enrollment occurred from February 1994 through January 1998 . The original reported number of 42 448 participants and 625 sites changed because 30 patients with poor documentation of informed consent were excluded ( 2 ) . Participants were assigned by a computer-generated r and omization schedule in a ratio of 1.7:1 to receive chlorthalidone or doxazosin . R and omization was stratified by center and blocked over time to maintain the ratio . All participants gave written informed consent , and all centers obtained institutional review board approval . Ascertainment of Outcomes At each clinic visit , occurrence of study end points was assessed by the clinical investigator . A hospital discharge summary was required for each hospitalized study outcome , and a death certificate was required for each death . ALLHAT defined symptomatic heart failure as clear-cut signs or symptoms of left or right ventricular dysfunction that can not be attributed to other causes . A patient had to have at least one symptom ( paroxysmal nocturnal dyspnea , dyspnea at rest , New York Heart Association class III dyspnea or other symptoms [ on less than ordinary exertion ] , or orthopnea ) and one sign ( rales , ankle edema , tachycardia , cardiomegaly or characteristic pulmonary pattern on chest radiography , S3 gallop , or jugular venous distention ) ( 3 ) . Symptoms and signs were determined by the clinic investigator through patient history , chart review , or consultation with the treating physician , but such data were not collected central ly . A one-time sample of 24 hospitalized or fatal heart failure events was review ed in a blinded manner by the ALLHAT Endpoints Subcommittee ; 20 of 24 ( 83 % ) were deemed to have complete data for a definitive diagnosis . Of the 20 cases , the agreement rate between the subcommittee and the clinic investigators was 90 % ( 18 of 20 ) and similar in both treatment groups . Details on the validity of diagnosis of heart failure will be provided in a future report . Measurement and Treatment of Blood Pressure The ALLHAT protocol specified a stepped-care treatment program for hypertension . Trained observers using st and ardized techniques measured blood pressures during the trial ( 1 , 2 ) . All blood pressures were calculated as the average of two measurements obtained with a 30-second interval between them . The blood pressure goal in all four study arms was less than 140/90 mm Hg . This level was to be achieved with the lowest possible dose of blinded first-line drug , with addition of second- and third-line open-label therapy as needed after reaching the maximal dose of first-line drug . Chlorthalidone and doxazosin were to be taken once daily in the morning . By design , doses were selected to achieve equivalent blood pressure control in the treatment groups . The first , second , and third dosage levels were 12.5 mg/d , 12.5 mg/d ( sham titration ) , and 25 mg/d , respectively , for chlorthalidone and 2 mg/d , 4 mg/d , and 8 mg/d for doxazosin . Double-blinded 1-mg and 12.5-mg doses of doxazosin and chlorthalidone , respectively , were used for the first week to minimize the frequency of postural hypotension associated with doxazosin . The identity of drugs was masked at each dosage level , but dosage level was not . After r and omization , patients were seen for dose titration as needed at 1 and 3 months per the protocol , but they could return more often until target blood pressure was reached . Subsequently , required visits occurred at 3-month intervals during the first year and at 4-month intervals thereafter . Open-label second-step drugs were added as needed and tolerated . These agents were reserpine ( 0.05 to 0.2 mg/d ) , clonidine ( 0.1 to 0.3 mg twice daily ) , and atenolol ( 25 to 100 mg/d ) . The choice of second-step drug was at the discretion of the treating clinician-investigator . The third-step agent was hydralazine ( 25 to 100 mg twice daily ) . Details of these therapies are provided elsewhere ( 1 ) . Investigators could choose to prescribe open-label antihypertensive drugs other than those provided by the study . However , use of the drug classes under study thiazide diuretics , calcium antagonists , angiotensin-converting enzyme inhibitors , and -adrenergic blockerswas strongly discouraged to avoid dilution of treatment comparisons . When clinical conditions other than uncontrolled hypertension ( for example , angina or heart failure ) were present , drugs from any study class could be used . If a step 1 drug was specifically required for blood pressure control while blinded drug treatment was continued , the step 1 drug could be added as open-label therapy but the dose could not exceed one half the maximum recommended by the Fifth Joint National Committee ( 4 ) . In most such cases , unblinding the patient or the investigator to treatment assignment was not necessary . ( Overall , < 1 % of drug identities were provided to either participant or investigator . ) Any of nine possible open-label drug typesdiuretic , calcium-channel blocker , angiotensin-converting enzyme inhibitor , -adrenergic blocker , atenolol , reserpine , clonidine , hydralazine , and other antihypertensive drug ( which could include nonatenolol -blockers , although drug name was not logged)could be recorded at each visit . Because diuretics , angiotensin-converting enzyme inhibitors , and -blockers are beneficial in preventing or treating heart failure , we call these antihypertensive heart failure drugs . Data on  antihypertensive drug use before study enrollment were collected , but not by drug class . Statistical Analysis Data were analyzed for use of additional drugs according to participants ' r and omized treatment assignments and regardless of continuation of blinded study treatment . The outcomes all heart failure ( treated outside hospital , hospitalized , or fatal ) and hospitalized or fatal heart failure were examined by treatment group for the entire cohort . The time to event for the previously published as-r and omized analyses was the interval from r and omization to first diagnosis of heart failure for patients who had an outcome , or from r and omization to ABBREVIATIONS A1C = hemoglobin A1C ; AACE = American Association of Clinical Endocrinologists ; ACCORD = Action to Control Cardiovascular Risk in Diabetes ; ACCORD BP = Action to Control Cardiovascular Risk in Diabetes Blood Pressure ; ACE = American College of Endocrinology ; ACEI = angiotensin-converting enzyme inhibitor ; AGI = alpha-glucosidase inhibitor ; apo B = apolipoprotein B ; ARB = angiotensin II receptor blocker ; ASCVD = atherosclerotic cardiovascular disease ; BAS = bile acid sequestrant ; BMI = body mass index ; BP = blood pressure ; CCB = calcium channel blocker ; CGM = continuous glucose monitoring ; CHD = coronary heart disease ; CKD = chronic kidney disease ; DKA = diabetic ketoacidosis ; DPP4 = dipeptidyl peptidase 4 ; eGFR = estimated glomerular filtration rate ; EPA = eicosapentaenoic acid ; ER = extended release ; FDA = Food and Drug Administration ; GLP1 = glucagon-like peptide 1 ;  HDL-C = high-density-lipoprotein cholesterol ; HeFH = heterozygous familial hypercholesterolemia ; LDL-C = low-density-lipoprotein cholesterol ; LDL-P = low-density-lipoprotein particle ; Look AHEAD = Look Action for Health in Diabetes ; NPH = neutral protamine Hagedorn ; OSA = obstructive sleep apnea ; PCSK9 = proprotein convertase subtilisin-kexin type 9 serine protease ; RCT = r and omized controlled trial ; SU = sulfonylurea ; SGLT2 = sodium-glucose cotransporter 2 ; SMBG = self-monitoring of blood glucose ; T2D = type 2 diabetes ; TZD = thiazolidinedione A large-scale , 8-week , open-label , clinical experience trial evaluated the efficacy of the angiotensin II receptor ( AT1 subtype ) blocker c and esartan cilexetil ( 16 to 32 mg once daily ) either alone or as add-on therapy in 6465 hypertensive patients . The study population was 52 % female and 16 % African American with a mean age of 58 years . It included 5,446 patients who had essential hypertension ( HBP ) and 1,014 patients who had isolated systolic hypertension ( ISH ) . These patients had either untreated or uncontrolled hypertension ( systolic blood pressure [ SBP ] 140 to 179 mm Hg or diastolic blood pressure [ DBP ] 90 to 109 mm Hg inclusive at baseline ) despite a variety of antihypertensive medications including diuretics , calcium antagonists , angiotensin converting enzyme ( ACE ) inhibitors , and alpha- or beta-blockers , either singly or in combination . The mean baseline blood pressure for the HBP group was 156/97 mm Hg . C and esartan cilexetil as monotherapy ( in 51 % of HBP patients ) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg . As add-on therapy ( in 49 % of HBP patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.8/11.3 mm Hg ) , calcium antagonists ( 16.6/11.2 mm Hg ) , beta-blockers ( 16.5/ 10.4 mm Hg ) , ACE inhibitors ( 15.3/10.0 mm Hg ) , alpha-blockers ( 16.4/10.4 mm Hg ) . The mean baseline blood pressure for the ISH group was 158/81 mm Hg . C and esartan cilexetil , as monotherapy ( in 34 % of ISH patients ) , reduced SBP/DBP by 17.0/4.4 mm Hg . As add-on therapy ( in 66 % of ISH patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.4/5.1 mm Hg ) , calcium antagonists ( 15.6/3.6 mm Hg ) , beta-blockers ( 14.0/4.8 mm Hg ) , ACE inhibitors ( 13.4/4.3 mm Hg ) , and alpha-blockers ( 11.6/4.5 mm Hg ) . The further blood pressure lowering effects of c and esartan cilexetil as add-on therapy were seen regardless of age , sex , and race . Overall , 6.8 % of the 6465 patients withdrew because of adverse events , most commonly headache ( 6.3 % ) and dizziness ( 5.0 % ) . Orthostatic hypotension was infrequent ; 0.2 % with c and esartan cilexetil alone , and 0.8 % with c and esartan cilexetil as add-on therapy . Thus , c and esartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice setting Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes .  Dihydropyridine calcium channel blockers , however , may lower blood pressure but not albuminuria in these patients . Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics . We conducted a double blind r and omized controlled trial on 332 hypertensive , albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year . The trial employed a non-inferiority design . Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort . The percentage of patients progressing to overt proteinuria was similar for both groups . When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria . We conclude that initial treatment using benzaepril with a diuretic result ed in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker . In contrast , blood pressure reduction , particularly the diastolic component , favored the combination with amilodipine . The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure OBJECTIVES The purpose of this study was to determine if statins ( hydroxymethylglutaryl CoA reductase inhibitors [ HMG-CoA ] ) , angiotensin-converting enzyme ( ACE ) inhibitors , and angiotensin receptor blockers ( ARBs ) reduce cardiovascular ( CV ) events and pulmonary morbidity in chronic obstructive pulmonary disease ( COPD ) patients . BACKGROUND Few current COPD therapies alter prognosis . Although statins , ACE inhibitors , and ARBs improve outcomes in CV population s , their benefits in COPD patients both with and without concomitant heart disease has not previously been studied . METHODS A time-matched nested case-control study of two population -based retrospective cohorts was undertaken : 1 ) COPD patients having undergone coronary revascularization ( high CV risk cohort ) ; and 2 ) COPD patients without previous myocardial infa rct ion ( MI ) and newly treated with nonsteroidal anti-inflammatory drugs ( low CV risk cohort ) . Prespecified outcomes were COPD hospitalization , MI , and total mortality . RESULTS These drugs reduced both CV and pulmonary outcomes , with the largest benefits occurring with the combination of statins and either ACE inhibitors or ARBs . This combination was associated with a reduction in COPD hospitalization ( risk ratio [ RR ] 0.66 , 95 % confidence interval [ CI ] 0.51 to 0.85 ) and total mortality ( RR 0.42 , 95 % CI 0.33 to 0.52 ) not only in the high CV risk cohort but also in the low CV risk cohort ( RR 0.77 , 95 % CI 0.67 to 0.87 , and RR 0.36 , 95 % CI 0.28 to 0.45 , respectively ) . The combination also reduced MI in the high CV risk cohort ( RR 0.39 , 95 % CI 0.31 to 0.49 ) . Benefits were similar when steroid users were included . CONCLUSIONS These agents may have dual cardiopulmonary protective properties , thereby substantially altering prognosis of patients with COPD . These findings need confirmation in r and omized clinical trials BACKGROUND Although beta-blockers and angiotensin-converting enzyme ( ACE ) inhibitors are often used together , there is a lack of quantitative evidence for the efficacy of this combination in reducing  blood pressure ( BP ) .  OBJECTIVE The aim of this r and omized , double-blind , placebo-controlled , crossover study was to quantify the combined effect of a beta-blocker ( atenolol ) and an ACE inhibitor ( lisinopril ) in lowering BP . METHODS Participants who were > or = 40 years of age and enrolled in the hypertension or anticoagulation clinics at St. Bartholomew 's Hospital , London , United Kingdom , were r and omized to 3 consecutive 4-week treatments consisting of atenolol 25 mg plus placebo , lisinopril 5 mg plus placebo , and atenolol 25 mg plus lisinopril 5 mg , plus a period of 2 placebos . At the end of each period , seated BP was measured in the right arm using electronic monitors . RESULTS The mean  placebo-adjusted peak BP reductions among the 47 participants ( mean age , 62 [ range 42 - 82 ] years ; 75 % male ; 70 % white/30 % Asian ; mean baseline BP , 145/82 mm Hg ) who completed all 4 periods were significantly greater with the combination of both drugs than with either drug alone ( P < 0.001 ) . The systolic reductions were 22.9 mm Hg with combination treatment , 16.1 mm Hg with atenolol treatment , and 12.5 mm Hg with lisinopril treatment , and the diastolic reductions were 13.9 , 9.8 , and 6.8 mm Hg , respectively . The BP-lowering effect of the 2 drugs together was similar to that expected from the sum of each alone , allowing for the reduced effect of 1 drug given the lower pretreatment BP due to the other . The incremental systolic BP reduction from the 2 drugs together compared with 1 alone was 79 % ( 95 % CI , 54%-126 % ) of the expected additive effect , 88 % ( 95 % CI , 58%-130 % ) for diastolic BP , and 84 % ( 95 % CI , 65%-118 % ) for the mean of systolic and diastolic BP . CONCLUSIONS The combination of the beta-blocker atenolol 25 mg plus the ACE inhibitor lisinopril 5 mg was associated with a significantly greater decrease in BP compared with either alone . The BP reduction with the combination treatment was similar to and statistically consistent with the 2 drugs having additive effects . Clinical Trials Identification Number : IS RCT N97280940 Objective . Angiotensin-converting enzyme ( ACE ) inhibitors have been shown to lower central augmentation index ( cAI ) , an index of arterial wave reflection , more than β-blockers . We tested whether this is also true for long-term treatment with an angiotensin receptor blocker ( ARB ) . Methods . One-hundred and fifty-six subjects with essential hypertension were r and omised to treatment with either irbesartan or atenolol .  cAI and central blood pressure ( BP ) were determined by pulse wave analysis from the radial and the carotid artery after six and after 18 months treatment . Results . Peripheral and central systolic and diastolic BP were reduced to a similar extent A in the two groups . cAI was reduced with irbesartan , but increased with atenolol ( derived from the carotid artery : -6±10 vs. -4±12 % after six months , p<0.001 ; —4±12 vs. + 1±11 % after 18 months ; p=0.011 ) . Furthermore , central to peripheral pulse pressure ( PP ) amplification was unaffected by treatment with irbesartan , but decreased with atenolol . Conclusions . Although treatment with irbesartan and atenolol  similarly decreased peripheral and central BP , only treatment with irbesartan had beneficial effects on arterial wave reflection and preserved PP amplification . These haemodynamic effects may at least partly explain the reported differential effects of ARB versus β-blocker treatment on cardiovascular mortality in patients with essential hypertension The Combination Therapy of Hypertension to Prevent Cardiovascular Events ( COPE ) trial demonstrated that the calcium-channel blocker benidipine-based combination therapies with an angiotensin-receptor blocker ( ARB ) , a β-blocker , or a thiazide diuretic ( thiazide ) were similarly effective in preventing cardiovascular events and achieving the target blood pressure ( BP ; < 140/90 mm Hg ) . We further evaluated the efficacy and safety of these combination therapies in older ( ⩾65 years ) and younger ( < 65 years ) hypertensive patients . In this sub- analysis of the COPE trial 3293 patients ( 1533⩾65 years old and 1760 < 65 years old ) were r and omly assigned to receive benidipine-based therapy with an ARB , a β-blocker or a thiazide . In each group , the average BP did not differ among the three treatment groups . The incidence of the primary cardiovascular composite end point in the older group was higher than in the younger group ( 12.7 vs. 8.3 per 1000 person-years , P=0.023 ) . The primary composite cardiovascular end point , achievement ( % ) of target BP , and cardiovascular hard composite end points were similar among the three treatment groups . However , the hazard ratios and 95 % confidence intervals in older patients were 2.74 ( 1.08–6.96 ; β-blocker vs. thiazide , P=0.022 ) for fatal and non-fatal stroke , and 2.47 ( 1.03–5.91 ; β-blocker vs. ARB , P=0.043 ) for new-onset diabetes . Thus , benidipine combined with an ARB , a β-blocker , or a thiazide was similarly effective in preventing cardiovascular events and achieving the target BP in both older and younger hypertensive patients . Further studies will be necessary to evaluate the usefulness of benidipine combined with a β-blocker in terms of the incidence of stroke and new-onset diabetes in older patients BACKGROUND Although most cardiovascular disease occurs in low-income and middle-income countries , little is known about the use of effective secondary prevention medications in these communities . We aim ed to assess use of proven effective secondary preventive drugs ( antiplatelet drugs , β blockers , angiotensin-converting-enzyme [ ACE ] inhibitors or angiotensin-receptor blockers [ ARBs ] , and statins ) in individuals with a history of coronary heart disease or stroke . METHODS In the Prospect i ve Urban Rural Epidemiological ( PURE ) study , we recruited individuals aged 35 - 70 years from rural and urban communities in countries at various stages of economic development . We assessed rates of previous cardiovascular disease ( coronary heart disease or stroke ) and use of proven effective  secondary preventive drugs  and blood-pressure-lowering drugs with st and ardised question naires , which were completed by telephone interviews , household visits , or on patient 's presentation to clinics . We report estimates of drug use at national , community , and individual levels . FINDINGS We enrolled 153,996 adults from 628 urban and rural communities in countries with incomes classified as high ( three countries ) , upper-middle ( seven ) , lower-middle ( three ) , or low ( four ) between January , 2003 , and December , 2009 . 5650 participants had a self-reported coronary heart disease event ( median 5·0 years previously [ IQR 2·0 - 10·0 ] ) and 2292 had stroke ( 4·0 years previously [ 2·0 - 8·0 ] ) . Overall , few individuals with cardiovascular disease took antiplatelet drugs  ( 25·3 % ) , β blockers ( 17·4 % ) , ACE inhibitors or ARBs ( 19·5 % ) , or statins ( 14·6 % ) . Use was highest in high-income countries ( antiplatelet drugs 62·0 % , β blockers 40·0 % , ACE inhibitors or ARBs 49·8 % , and statins 66·5 % ) , lowest in low-income countries ( 8·8 % , 9·7 % , 5·2 % , and 3·3 % , respectively ) , and decreased in line with reduction of country economic status ( p(trend)<0·0001 for every drug type ) . Fewest patients received no drugs in high-income countries ( 11·2 % ) , compared with 45·1 % in upper middle-income countries , 69·3 % in lower middle-income countries , and 80·2 % in low-income countries . Drug use was higher in urban than rural areas ( antiplatelet drugs 28·7 % urban vs 21·3 % rural , β blockers 23·5%vs 15·6 % , ACE inhibitors or ARBs 22·8%vs 15·5 % , and statins 19·9%vs 11·6 % ; all p<0·0001 ) , with greatest variation in poorest countries ( p(interaction)<0·0001 for urban vs rural differences by country economic status ) . Country-level factors ( eg , economic status ) affected rates of drug use more than did individual-level factors ( eg , age , sex , education , smoking status , body-mass index , and hypertension and diabetes statuses ) . INTERPRETATION Because use of secondary prevention medications is low worldwide-especially in low-income countries and rural areas - systematic approaches are needed to improve the long-term use of basic , inexpensive , and effective drugs . FUNDING Full funding sources listed at end of paper ( see Acknowledgments ) The African American Study of Kidney Disease and Hypertension ( AASK ) is a multicenter r and omized clinical trial design ed to test the effectiveness of three anti-hypertensive drug regimens and two levels of BP control on the progression of hypertensive kidney disease . Participants include African-American men and women aged 18 to 70 yr who have hypertensive kidney disease and GFR between 20 and 65 ml/min per 1.73 m(2 ) . The three anti-hypertensive drug regimens include an angiotensin converting enzyme inhibitor ( ramipril ) , a dihydropyridine calcium channel blocker ( amlodipine ) or a beta-blocker ( metoprolol ) as initial therapy . The BP control levels are a lower goal ( mean arterial pressure , < /=92 mmHg ) and a usual goal ( mean arterial pressure , 102 to 107 mmHg inclusive ) . The primary outcome is rate of change in renal function as measured by GFR , assessed by ( 125 ) I-iothalamate clearance . The main secondary patient outcome is a composite including the following events : ( 1 ) reduction in GFR by 50 % , ( 2 ) end-stage renal disease , or ( 3 ) death The renin-angiotensin-aldosterone system ( RAAS ) is an established mediator of progressive renal and cardiovascular disease . Angiotensin II plays a key role in the progression of cardiovascular and renal disease , and drugs that interfere with angiotensin II actions such as angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin receptor blockers ( ARBs ) can offer cardiovascular and renal protection beyond their effects on blood pressure . 1–6 Recently , a number of experimental and clinical investigations have implicated aldosterone , independent of angiotensin II , in the pathogenesis of progressive  cardiovascular and renal disease . 7–9 These studies have generated intense interest in aldosterone receptor antagonism , either alone or in combination with an ACEI or an ARB , in the treatment of a wide range of cardiovascular diseases as well as progressive renal injury . Blockade of the renin-angiotensin system ( RAS ) with either an ACEI or an ARB is important in patients with hypertension , heart failure , myocardial infa rct ion , stroke , and various forms of nephropathy , the most common of which is due to diabetes mellitus . Support for RAS blockade derives from large r and omized , controlled , clinical trials demonstrating that these agents attenuate progression of renal disease . 1–6 Lowering blood The Treatment of Mild Hypertension Study ( TOMHS ) is a r and omized , double-blind clinical trial currently being conducted to compare the effects of nonpharmacologic therapy alone with those of 1 of 5 active drug regimens combined with nonpharmacologic therapy , for long-term management of patients with mild hypertension . Six classes of drugs were studied : ( 1 ) acebutolol ( beta blocker ) , ( 2 ) amlodipine ( calcium antagonist ) , ( 3 ) chlorthalidone ( diuretic ) , ( 4 ) doxazosin ( alpha 1 antagonist ) , ( 5 ) enalapril ( angiotensin-converting enzyme inhibitor ) and ( 6 ) placebo . All participants received nutritional-hygienic advice to reduce weight and sodium and alcohol intakes and to increase physical activity . End points include blood pressure change , side effects and quality -of-life indices ; incidence of electrocardiographic and echocardiographic abnormalities ; and incidence of cardiovascular clinical events , including death , among participants receiving drugs as first-step treatment as well as nonpharmacologic treatment compared with incidence among those participants r and omized to nonpharmacologic treatment only as the initial step BACKGROUND Addition of spironolactone ( SPR ) to angiotensin-converting enzyme ( ACE ) inhibitors or angiotensin II receptor blockers ( ARBs ) might provide antiproteinuric effects beyond what is gained by either medication alone . This study was design ed to assess the long-term efficacy of SPR/ARB combination in comparison with the st and ard ACE/ARB regimen in diabetic nephropathy . METHODS In an open-label , parallel-group , single-center , r and omized clinical trial ( NCT01667614 ) , 136 patients with diabetes and proteinuria , already treated with enalapril and losartan , were included . In 74 patients , ACE inhibitors  were discontinued . After a wash-out period of 2 weeks , 25 mg SPR daily was initiated . The remainder of the patients ( n = 62 ) received ACE inhibitors and ARBs as before . Patients were followed every 3 months for 18 months . During each visit , systolic and diastolic blood pressure ( BP ) , urinary albumin excretion ( UAE ) , serum creatinine , estimated glomerular filtration rate ( eGFR ) and serum potassium concentrations were determined . RESULTS After 18 months , three patients in the SPR/ARB group developed asymptomatic hyperkalemia .  SPR/ARB significantly reduced both systolic and diastolic BP ( P < 0.001 and 0.001 , respectively ) . SPR/ARB  decreased UAE by 46 , 72 and 59 % after 3 , 12 and 18 months , respectively . Compared with the continuation regimen , SPR/ARB was superior in UAE reduction ( P = 0.017 after 18 months ) , independent of BP change . In both groups , eGFR declined significantly over the trial course and the decline rate did not differ significantly between the two groups . CONCLUSIONS Addition of SPR to ARB provides added benefits with respect to BP control and proteinuria diminution . These antiproteinuric effects are not accompanied by prevention of eGFR loss compared with conventional therapy with ACE/ARB BACKGROUND Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics , beta-blockers , angiotensin-converting enzyme inhibitors , central alpha-agonists , and other vasodilators . Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal . METHODS A three-phase , r and omized , double-blind , placebo-controlled  multicenter study included 162 patients aged 18 to 75 years with essential hypertension . After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride , patients received ibuprofen , naproxen , or placebo matching capsules for 3 weeks , and blood pressure , heart rate , weight , and adverse effects were evaluated . A general linear model with 95 % confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group . RESULTS No significant differences in sitting , st and ing , or supine blood pressure were noted with naproxen or ibuprofen compared with placebo . The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar . Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies . Changes in pulse rate were not significant . The incidence of adverse effects was similar across all three treatment groups . CONCLUSIONS The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure .  Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy Objective : A case control study has reported a 60 % higher risk of myocardial infa rct ion in hypertensives treated with a calcium channel blocker ( CCB ) . We examined the Department of Health Hypertension Care Computing Project ( DHCCP ) data to see if we could confirm or refute this suggestion . Design : Two case control studies , matched and unmatched , plus two longitudinal studies from 1 year of presentation , one for all subjects given a CCB  for more than 1 year compared with those not given this drug , and the second comparing survival on the different drugs initially given between 3 and 12 months of follow-up . Subjects : A total of 9328 subjects were included in the analyses and 2154 died . Of these , 6406 received one or more of the following index drugs : 26 % a calcium channel blocker ( CCB ) ; 84 % a diuretic ; 29 % alpha methyldopa ; 12 % a beta-blocker ( BB ) ; and 11 % an angiotensin-converting enzyme ( ACE ) inhibitor . The CCBs were nifedipine , diltiazem or verapamil . Results : In the case control studies a group given diuretics ± other treatments ( but not including one of the index drugs ) provided a reference group with a relative risk ( RR ) of 1.0 . In the matched case control study the adjusted RR for a CCB  without a diuretic was 1.32 ( 95 % CI 0.64–2.70 ) for IHD mortality and 1.05 ( 95 % CI 0.60–1.84 ) for cardiovascular mortality . Similar results were observed for methyldopa , BBs and ACE inhibitors . The results in the unmatched case control analysis were also similar . The longitudinal study comparing all those treated for over 1 year with a CCB with all other treatments showed a RR for total mortality of 1.03 ( 95 % CI 0.85–1.25 ) . The longitudinal study of total mortality according to treatment initiated at 3–12 months found results of a similar magnitude for CCBs , methyldopa and BBs . Conclusions : The reference diuretic group had less severe cardiovascular disease than other groups . Treatment with a CCB , BB or methyldopa was associated with an excess mortality in comparison with this reference group . The excess was similar in the different drug groups BACKGROUND Women 's long-term patterns of evidence -based preventive medication utilization following a coronary heart disease ( CHD ) diagnosis have not been sufficiently studied . METHODS Postmenopausal women 50 - 79 years were eligible for r and omization in the Women 's Health Initiative 's ( WHI ) hormone trials if they met inclusion and exclusion criteria and were > 80 % adherent during a  placebo-lead-in period and in the dietary modification trial if they were willing to follow a 20 % fat diet .  Those with adjudicated myocardial infa rct ion or coronary revascularization after the baseline visit were included in the analysis ( n=2627 ) . Baseline visits occurred between 1993 and 1998 , then annually until the trials ended in 2002 through 2005 ; medication inventories were obtained at baseline and years 1 , 3 , 6 and 9 . RESULTS Utilization at the first WHI visit following a CHD diagnosis increased over time for statins ( 49 % to 72 % ; p<0.0001 ) , beta-blockers ( 49 % to 62 % ; p=0.003 ) , and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers ( ACEI/ARBs ) [ 26 to 43 % ; p<0.0001 ] . Aspirin use remained stable at 76 % ( p=0.09 ) . Once women reported using a statin , aspirin , or beta-blocker , 84 - 89 % reported use at 1 or more subsequent visits , with slightly lower rates for ACEI/ARBS ( 76 % ) .  Statin , aspirin , beta-blocker , or ACEI/ARB use was reported at 2 or more consecutive visits by 57 % , 66 % , 48 % , and 28 % respectively . These drugs were initiated or resumed at a later visit by 24 % , 17 % , 15 % , and 17 % , respectively , and were never used during the period of follow-up by 19 % , 10 % , 33 % , and 49 % respectively . CONCLUSIONS Efforts to improve secondary prevention medication utilization should target both drug initiation and restarting drugs in patients who have discontinued them OBJECTIVE To evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension . METHODS After 2-week wash-out , a total of 370 patients with seated diastolic blood pressure 95 - 114 mmHg and seated systolic blood pressure < 180 mmHg were r and omized to different therapeutic groups .  24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks . RESULT All the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin , terazosin , and torasemide . CONCLUSION The result suggested that the angiotensin-converting enzyme inhibitors , angiotensin II receptor blockers , beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension , while the low-dose doxazosin , terazosin and torasemide can be used for combination therapy but not for monotherapy Introduction : The optimal combination treatment for hypertension has not been established . We investigated the effect of a calcium channel blocker or a diuretic added to angiotensin II receptor blockers ( ARBs ) on the augmentation index ( AI ) , as a marker of arterial stiffness and wave reflection , in hypertensive patients . Methods : Thirty-seven patients treated with ARBs  were r and omly allocated to either of the 2 groups receiving an ARB plus azelnidipine ( AZ group ) or trichlormethiazide ( TCM group ) . Changes in brachial blood pressure ( BP ) , AI , high-sensitive C-reactive protein ( hsCRP ) , and serum asymmetric dimethylarginine , as an endogenous nitric oxide synthase inhibitor , were determined . Results : Systolic and diastolic blood pressure after 6 months were significantly reduced in both the groups similarly ; however , after adjustment for baseline covariates , the extent of the reduction in AI ( % ) in the AZ group was significantly greater than in the TCM group ( between-group difference was 3.2 ; 95%CI : 0.2–6.3 ; P = 0.03 ) . The reduction of high-sensitive C-reactive protein ( mg/L ) and serum asymmetric dimethylarginine ( & mgr;mol/L ) was significantly greater in the AZ group than in the TCM group ( between-group difference was 0.18 and 0.05 ; 95%CI : −0.01 to 0.36 and −0.01 to 0.11 ; P = 0.04 and 0.02 , respectively ) . Further , when patients were analyzed according to age younger than 60 years or older than 60 years , the reduction in AI in the AZ group aged older than 60 years was significantly greater than in the TCM group . Conclusion : The results suggest that azelnidipine has a more beneficial effect on vascular properties in combination therapy with ARB than trichlormethiazide PURPOSE Patterns of antihypertensive drug use in patients undergoing long-term hemodialysis therapy were studied . METHODS Patients attending seven outpatient hemodialysis units in Ohio were eligible for the study if they had been receiving the treatment for at least three months . Demographic and clinical data were obtained from patient interviews and computerized data bases , and blood pressure ( BP ) measurements were obtained before dialysis . Labeled names and dosages of antihypertensive drugs were recorded from containers the patients brought with them . Patients were asked to describe their adherence to the medications , their ability to afford the drugs , and their knowledge and beliefs about hypertension . Physical impairments in taking medication were also evaluated . RESULTS The frequency of hypertension was 89 % in the 270 participants . Antihypertensive drugs were prescribed for 76 % of the patients ; 25 % required three or more drugs . Hypertensive patients who were not receiving antihypertensive drugs ( 14 % ) had significantly higher BP than patients who were . Calcium-channel blockers were prescribed for 60 % of patients , angiotensin-converting-enzyme inhibitors for 33 % , and beta-blockers for 34 % . Eighty-three percent said the cost of drugs was never a problem , and 23 % said they sometimes forgot to take their medication . Almost all patients said they would not stop taking antihypertensive drugs if they were feeling better and agreed that monitoring BP was important . Twenty-two percent could not read the warning on a st and ard tablet container , and 12 % could not remove one tablet from the container . CONCLUSION Multidrug antihypertensive therapy was common among hemodialysis patients and was associated with significantly lower BP ; calcium-channel blockers were the most frequently prescribed agents . Most patients said they could afford drugs and reported good adherence to antihypertensive drug therapy While the safety of renin-angiotensin system (RAS)-blocking drugs such as angiotensin-converting enzyme ( ACE ) inhibitors and angiotensin receptor blockers is well known , less is known about the new direct renin inhibitor aliskiren . The authors pooled data from 12 r and omized controlled trials of aliskiren in patients with hypertension and analyzed the incidence and types of adverse events ( AEs ) and laboratory abnormalities . Studies were characterized as short-term ( ≤2 months ) placebo-controlled or long-term ( > 2 months ) active-controlled . Relative risks for AEs of particular interest for RAS blockers were calculated . In short-term studies , AEs occurred in similar proportions of aliskiren 150 mg and 300 mg ( 33.6 % and 31.6 % , respectively ) and placebo treatment groups ( 36.8 % ) . In long-term studies , a lower proportion of patients treated with aliskiren 150 mg and 300 mg had AEs ( 33.7 % and 43.2 % , respectively ) than those treated with ACE inhibitors ( 60.1 % ) , angiotensin receptor blockers ( 53.9 % ) , and thiazide diuretics ( 48.9 % ) . Events of special interest , including angioedema , hyperkalemia , and diarrhea occurred in similar proportions of patients taking aliskiren , placebo , and comparator agents . In studies of up to 36 weeks , patients treated with aliskiren were significantly less likely to develop cough than those treated with ACE inhibitors . At the registered doses of 150 mg and 300 mg daily , aliskiren  has safety and tolerability profiles  similar to placebo , other RAS blockers , and diuretics . Cough rates are lower with aliskiren compared with ACE inhibitors BACKGROUND We are investigating whether aldosterone breakthrough negatively impacts on the antiproteinuric effects of angiotensin-converting enzyme ( ACE ) inhibitors and /or angiotensin II receptor blockers ( ARB ) . METHODS We examine the role of aldosterone breakthrough in 43 normotensive , proteinuric ( 0.7 + /- 0.3 g/day ) out patients ( aged 41.5 + /- 10.9 years ) with immunoglobulin A nephropathy ( IgAN ) accompanied by stable renal function ( creatinine clearance > 50 mL/min ) . The patients were treated with temocapril ( 1 mg ; n = 14 ) , losartan ( 12.5 mg ; n = 16 ) , or a combination therapy ( n = 13 ) for 12 months . We prospect ively evaluated blood pressure ( BP ) , urinary protein excretion ( UPE ) , biochemical parameters and the renin-angiotensin-aldosterone system before and after 12 months of treatment . RESULTS Although the overall plasma aldosterone concentrations values did not change after any of the treatments administered for 12 months , they eventually increased in 23 ( temocapril , seven patients ; losartan , eight patients ; combination , seven patients ) of the 43 patients ( 53.4 % ; aldosterone breakthrough ) , and fell in the remainder ( 46.6 % ) . Blood pressure and renal function did not differ among the three groups at 12 months . In contrast , UPE was significantly higher in patients with , than without aldosterone breakthrough during temocapril and losartan administration . However , combination therapy induced a more remarkable reduction in UPE regardless of aldosterone breakthrough . CONCLUSIONS A combination of ACE inhibitors and ARB in normotensive patients with IgAN produces a more profound decrease in proteinuria than either monotherapy . This additive antiproteinuric effect is not dependent on aldosterone breakthrough . Additional larger , prospect i ve , r and omized studies will be needed for general acceptance of this strategy Higher doses of angiotensin II receptor blockers ( ARBs ) are expected to exert more protective effects against cardiovascular diseases . However , the significance of treatment of hypertension with high-dose ARB remains to be defined . The OlmeSartan and Calcium Antagonists R and omized ( OSCAR ) Study was design ed to determine whether high-dose ARB monotherapy is superior to the combination therapy of ARB plus calcium channel blocker ( CCB ) in the prevention of cardiovascular morbidity/mortality in Japanese elderly high-risk hypertensive patients . The OSCAR study is a multicenter , active-controlled , two-arm parallel group comparison , using the prospect i ve r and omized open-blinded end-point method . In the ‘ Step 1 ’ period , elderly hypertensive patients with diabetes or cardiovascular disease received monotherapy with ARB olmesartan medoxomil at a dose of 20 mg day−1 . If the target blood pressure control ( less than 140/90 mm Hg ) was not achieved by ARB monotherapy , the patients were r and omized to receive either ( 1 ) the increased dose of olmesartan at 40 mg day−1 ( high-dose ARB monotherapy ) or ( 2 ) the addition of a CCB ( amlodipine or azelnidipine ) to 20 mg day−1 olmesartan ( ARB plus CCB combination ) in the ‘ Step 2 ’ period . The follow-up duration will be 3 years . The primary end points will be the composite of fatal and non-fatal cardiovascular events , and death from any cause .  Recruitment for the OSCAR study ( around 1200 patients ) was completed by the end of May 2007 . The OSCAR study is the first large clinical trial comparing the efficacy of high-dose ARB monotherapy with that of an ARB plus CCB combination therapy in elderly high-risk hypertensive patients Chronic kidney disease ( CKD ) in heart failure ( HF ) increases the risk of hyperkalaemia ( HK ) , limiting angiotensin‐converting enzyme inhibitor ( ACE‐I ) or angiotensin receptor blocker ( ARB ) use . Patiromer is a sodium‐free , non‐absorbed potassium binder approved for HK treatment . We retrospectively evaluated patiromer 's long‐term safety and efficacy in HF patients from AMETHYST‐DN Abstract We compared the efficacy of treatment protocol s with an angiotensin converting enzyme ( ACE ) inhibitor alone ( enalapril , 5 mg ) or angiotensin II ( ATII ) receptor blocker ( losartan , 50 mg ) or both enalapril plus losartan in patients with microalbuminuria in a prospect i ve , r and omized clinical trial . Normotensive type 2 diabetic patients with microalbuminuria documented by at least 3 consecutive urinary albumin excretion analyses were recruited for the study . Patients were grouped r and omly into one of the protocol s which consisted of treatment with 5 mg enalapril daily ( group 1 ; n=12 ) , 50 losartan daily ( group 2 ; n=12 ) or both drugs ( group 3 ; n=10 ) . They were reevaluated with regard to HbA1c levels , lipid profiles , blood pressure and urinary albumin excretion rates ( UAER ) at 3-month intervals for 12 months . Mean age , duration of diabetes , body mass index , plasma lipid profiles and blood pressure levels were similar at the initial visit . In group 1 , UAER returned to normal levels in 10 patients . Normalization of UAER occurred in 8 and 7 patients in groups 2 and 3 , respectively . Percentage of reduction in UAERs at the end of 12 months were 58 % , 59 % and 60 % ( p=0.0001 ; p=0.0002 ; p=0.0003 , respectively ) . The amount of reduction in UAER did not differ significantly among the three groups ( p=0.346 ) . ACE inhibitors and angiotensin II receptor blockers have similar efficacy in treating diabetic microalbuminuria , and the combination of the two drugs does not add any further benefit The drug treatment of heart failure , once simple , has become complex . Apart from a loop diuretic and digoxin , most patients should now be receiving an angiotensin-converting enzyme inhibitor ( or angiotensin II receptor blocker ) , a beta-blocker and spironolactone . Newer drugs , such as endothelin-receptor antagonists and combined blockers of converting-enzyme and neutral endopeptidase , might soon become available . When to introduce these drugs and what dose is optimal for any individual , are questions that currently vex clinicians . We proposed that plasma levels of the cardiac hormone brain natriuretic peptide ( BNP , or better , its 1 - 76 amino-acid N-terminal fragment , N-BNP ) , would provide an objective index for guiding drug treatment in patients with established , stable cardiac failure . In a pilot study , 69 patients were r and omized to drug treatment based on clinical criteria , or based on plasma levels of N-BNP .  After a median follow-up of 9.6 months , those in the N-BNP group had fewer clinical end-points than those in the group managed by clinical criteria alone ( 19 vs 54 ; P= 0.02 ) . These preliminary data encourage the concept that the increasingly complex pharmacotherapy for heart failure , both chronic ( as in this trial ) and acute , might best be guided by an objective measure such as plasma levels of BNP or N-BNP Background Coronary heart disease ( CHD ) is one of the most common long-term complications in people with type 2 diabetes . We analyzed whether or not gender differences exist in diabetes and CHD medication among people with type 2 diabetes . Methods The study was based on data from the baseline examination of the DIANA study , a prospect i ve cohort study of 1,146 patients with type 2 diabetes conducted in South-West Germany . Information on diabetes and CHD medication was obtained from the physician question naires . Bivariate and multivariate analyses using logistic regression were employed in order to assess associations between gender and prescribed drug classes . Results In total , 624 men and 522 women with type 2 diabetes with a mean age of 67.2 and 69.7 years , respectively , were included in this analysis . Compared to women , men had more angiopathic risk factors , including smoking , alcohol consumption and worse glycemic control , and had more often a diagnosed CHD . Bivariate analyses showed higher prescription of thiazolidinediones and oral combination drugs  as well as of  angiotensin-converting enzyme ( ACE ) inhibitors , calcium channel blockers and aspirin  in men than in women . After full adjustment , differences between men and women remained significant only for ACE inhibitors ( OR = 1.44 ; 95%-confidence interval ( CI ) : 1.11 – 1.88 ) and calcium channel blockers ( OR = 1.42 , 95%-CI : 1.05 – 1.91 ) . Conclusions These findings contribute to current discussion s on gender differences in diabetes care . Men with diabetes are significantly more likely to receive  oral combination drugs , ACE inhibitors and calcium channel blockers  in the presence of coronary heart disease , respectively . Our results suggest , that diabetic men might be more thoroughly treated compared to women . Further research is needed to focus on reasons for these differences mainly in treatment of cardiovascular diseases to improve quality of care OBJECTIVE To assess the association between  first myocardial infa rct ion and the use of antihypertensive agents .  DESIGN AND SETTING We conducted a population -based case-control study among enrollees of the Group Health Cooperative of Puget Sound ( GHC ) . PATIENTS AND METHODS Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infa rct ion from 1986 through 1993 among women and from 1989 through 1993 among men . Controls were a stratified r and om sample of hypertensive GHC enrollees , frequency matched to the cases on age , sex , and calendar year . All 623 cases and 2032 controls had pharmacologically treated hypertension . Data collection included a review of the ambulatory medical record a brief telephone interview of consenting survivors . Antihypertensive therapy was assessed using the GHC 's computerized pharmacy data base . RESULTS The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease . Compared with users of diuretics alone , the adjusted risk ratio of myocardial infa rct ion was increased by about 60 % among users of calcium channel blockers with or without diuretic ( risk ratio = 1.62 % ; 95 % confidence interval [ Cl ] , 1.11 to 2.34 ; P = .01 ) . The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a beta-blocker .  Among these subjects , the use of calcium channel blockers compared with beta-blockers was associated with about a 60 % increase in the adjusted risk of myocardial infa rct ion ( risk ratio = 1.57 ; 95 % Cl , 1.21 to 2.04 ; P < .001 ) . While high doses of beta-blockers were associated with a decreased risk of myocardial infa rct ion ( trend P = .04 ) , high doses of calcium channel blockers were associated with an increased risk ( trend P < .01 ) . CONCLUSIONS In this study of hypertensive patients , the use of short-acting calcium channel blockers , especially in high doses , was associated with an increased risk of myocardial infa rct ion . Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies , including calcium channel blockers , on several important cardiovascular end points . Until these results are available , the findings of this study support the current guidelines from the Joint National Committee on the Detection , Evaluation and Treatment of High Blood Pressure that recommend diuretics and beta-blockers as first-line agents unless contraindicated , unacceptable , or not tolerated Angiotensin converting enzyme inhibitors ( ACE-Is ) and angiotensin II receptor blockers ( ARBs ) are frequently used for the treatment for glomerulonephritis and diabetic nephropathy because of their albuminuria- or proteinuria-reducing effects . To many patients who are nonresponsive to monotherapy with these agents , combination therapy appears to be a good treatment option . In the present study , we examined the effects of the addition of an ARB ( losartan ) followed by titration upon addition and at 3 and 6 months ( n=14 ) and the addition of an ACE-I followed by titration upon addition and at 3 and 6 months ( n=20 ) to the drug regimen treatment protocol in type 2 diabetic patients with nephropathy for whom more than 3-month administration of an ACE-I or the combination of an ACE-I plus a conventional antihypertensive was ineffective to achieve a blood pressure ( BP ) of 130/80 mmHg and to reduce urinary albumin to < 30 mg/day . During the 12-month treatment , addition of losartan or addition of an ACE-I to the treatment protocol reduced systolic blood pressure ( SBP ) by 10 % and 12 % , diastolic blood pressure ( DBP ) by 7 % and 4 % , and urinary albumin excretion by 38 % and 20 % of the baseline value , respectively . However , the effects on both BP and urinary albumin were not significantly different between the two therapies . In conclusion , addition of losartan or an ACE-I to an ongoing treatment with an ACE-I , or addition of an ACE-I to ongoing treatment with a conventional antihypertensive were equally effective at reducing the urinary albumin excretion and BP , and provided renal protection in patients with type-2 diabetic nephropathy We investigated whether angiotensin II receptor blockers ( ARBs ) and angiotensin converting enzyme inhibitors ( ACE-Is ) are more strongly associated with Alzheimer 's disease ( AD ) , vascular dementia ( VaD ) , and other dementias , than other anti-hypertensive drugs . We conducted a nested case-control analysis within the UK general practice research data base , with prospect ively recorded anti-hypertensive prescribing data . We sample d cases aged ≥60 years and diagnosed between 1997 - 2008 ( 5,797 with AD , 2,186 with VaD , 1,214 with unspecified/other dementia ) which were matched to up to four controls by age , general practice and gender . We computed odds-ratios and dose response effects for AD , vascular and unspecified/other dementia , comparing those prescribed ARBs or ACE-Is for at least six months with patients prescribed other anti-hypertensives . We controlled for matching factors , co-morbidities , smoking status , an area measure of socioeconomic status , consultation rate and blood pressure and accounted for reverse causality by introducing time-lags of up to eight years prior to diagnosis/index date . Patients diagnosed with AD , vascular and unspecified/other dementia had fewer prescriptions for ARBs and ACE-Is . Inverse associations with AD were strongest for ARBs ( odds-ratio ; 0.47 , 95%CI , 0.37 - 0.58 ) compared with ACE-Is ( odds-ratio ; 0.76 , 95%CI , 0.69 - 0.84 ) ( p(difference ) < 0.001 ) . Associations of ARBs with AD were stronger than for vascular dementia ( p(difference ) = 0.01 ) and unspecified/other dementia ( p(difference ) = 0.23 ) . There were inverse dose-response relationships between ARBs and ACE-Is with AD ( both p(trend ) < 0.01 ) . The inverse association of ACE-Is with AD diminished when using longer time lags but the ARB-AD association persisted . Patients with AD were around half as likely to be prescribed ARBs . Further r and omized controlled trial evidence is required to rigorously test these findings Aims To assess the efficacy of an angiotensin converting enzyme ( ACE ) inhibitor ( perindopril ) , a dihydropyridine calcium channel blocker ( sustained release nifedipine ) and placebo in preventing the progression of albuminuria and decline in glomerular filtration rate ( GFR ) in patients with Type 2 diabetes and microalbuminaria BACKGROUND The present multicenter study investigated whether the combination of angiotensin-converting enzyme inhibitor ( ACEI ) and angiotensin II receptor blocker ( ARB ) is more beneficial for preventing left ventricular remodeling and suppressing neurohumoral factors than either ACEI or ARB alone . METHODS AND RESULTS One hundred and six patients with mild-to-moderate congestive heart failure treated in 26 Japanese institutes were r and omly assigned to the combination therapy or monotherapy .  Changes in physical activity ( New York Heart Association functional classes , Specific Activity Scale ( SAS ) ) , concentrations of neurohumoral factors ( plasma renin activity , angiotensin II , aldosterone , and brain natriuretic peptide ( BNP ) ) , and cardiac function for 6 months were compared between the 2 groups . It was found that the combination therapy , which was administered at doses st and ard in Japan , increased the SAS score ( 4.5 + /- 1.5 to 4.9 + /- 1.5 , p<0.05 ) and decreased the plasma BNP concentration ( 183 + /- 163 to 135 + /- 118 pg/ml , p<0.05 ) . In contrast , there were no changes in SAS score ( 4.5 + /- 1.4 to 4.6 + /- 1.4 , NS ) or BNP concentration ( 156 + /- 157 to 151 + /- 185 pg/ml , NS ) in the patients receiving monotherapy . CONCLUSIONS The results of the study demonstrate that the combination therapy , even at the st and ard doses for Japan , improves physical activity and plasma BNP concentration more than the monotherapy . A larger study is required to assess the effects of the combination therapy on major clinical outcomes Evaluation of safety and efficacy of new drugs is based largely on data from clinical trials involving a limited number of patients . This approach does not necessarily detect the rare adverse events that may only be observed when very large numbers of patients are studied . Consequently , we design ed a double-blind 12-week trial comparing the new angiotensin-converting enzyme ( ACE ) inhibitor , quinapril ( n = 5,053 ) , with a well-established beta-adrenergic receptor blocker , metoprolol  ( n = 506 ) . Essentially hypertensive patients ( diastolic blood pressure 95 - 114 mm Hg ) received either 10 mg quinapril or 50 mg metoprolol once daily , and the doses were doubled at 4-week intervals to a maximum of 40 and 200 mg , respectively , in nonresponders . Responder rates were similar under both regimens . Adverse events were assessed by interview as well as by a st and ard question naire . The overall prevalence of adverse events reported by st and ard question naire was higher than that reported spontaneously during interviews . With respect to typical ACE inhibitor adverse reactions ( e.g. cough and taste disturbances ) , there was no difference between quinapril and metoprolol independent of the mode of reporting . In summary , both drugs showed comparable overall tolerance and safety . The discrepancy between spontaneously reported and question naire-reported adverse events was noteworthy , and this finding prevailed in a volunteer group of 327 patients who were treated with quinapril for 52 weeks . Thus , a question naire is of great significance in addition to the patient history/interview in a large-scale , double-blind study design ed to learn about details of drug safety To determine the antihypertensive benefit of adding low dose sprinolactone to multi-drug regimens that included a diuretic , a calcium channel blocker and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in patients with moderately severe chronic kidney disease ( CKD ) [ glomerular filtration rate ( GFR ) 25 - 50 mL/min ] and resistant hyper-tension , we studied 41 patients r and omly divided into two groups : group 1 : patients who received  placebo as spironolactone  and group 2 : patients who received spironolactone 25 - 50 mg/day . The patients were evaluated during follow-up at the 6th and 12th weeks . The mean decrease in systolic and diastolic blood pressure after 6 weeks of spironolactone was 33 ± 8 and 13 ± 2 mmHg , respectively , and it was maintained after 12 weeks of spironolactone wherein the values were 36 ± 10 and 12 ± 2 mmHg , respectively , while there was no change in the blood pressure in the control group . Hyperkalemia ( serum potassium > 5.5 meq/L ) occurred in one subject in the spironolactone group . We conclude that low-dose spironolactone may provide a significant additive blood pressure reduction in CKD patients ( stage 2 and 3 ) with resistant hypertension Notwithst and ing the availability of antihypertensive drugs and practice guidelines , blood pressure control remains suboptimal . The complexity of current treatment guidelines may contribute to this problem . To determine whether a simplified treatment algorithm is more effective than guideline -based management , we studied 45 family practice s in southwestern Ontario , Canada , using a cluster r and omization trial comparing the simplified treatment algorithm with the Canadian Hypertension Education Program guidelines . The simplified treatment algorithm consisted of the following : ( 1 ) initial therapy with a low-dose angiotensin-converting enzyme inhibitor/diuretic or angiotensin receptor blocker/diuretic combination ; ( 2 ) up-titration of combination therapy to the highest dose ; ( 3 ) addition of a calcium channel blocker and up-titration ; and ( 4 ) addition of a non — first-line antihypertensive agent . The proportion of patients treated to target blood pressure ( systolic blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg for patients without diabetes mellitus or systolic blood pressure < 130 mm Hg and diastolic blood pressure < 80 mm Hg for diabetic patients ) at 6 months was analyzed at the practice level . The proportion of patients achieving target was significantly higher in the intervention group ( 64.7 % versus 52.7 % ; absolute difference : 12.0 % ; 95 % CI : 1.5 % to 22.4 % ; P=0.026 ) . Multivariate analysis of patient-level data showed that assignment to the intervention arm increased the chance of reaching the target by 20 % ( P=0.028 ) , when adjusted for other covariates . In conclusion , the Simplified Treatment Intervention to Control Hypertension Study indicates that a simplified antihypertensive algorithm using initial low-dose fixed-dose combination therapy is superior to guideline -based practice for the management of hypertension BACKGROUND The aim of the present study was to assess the effects of angiotensin II receptor blocker ( ARB ) on coronary plaque progression in patients with acute myocardial infa rct ion ( AMI ) who received an angiotensin-converting enzyme inhibitor ( ACEI ) .  METHODS AND RESULTS After local ethics committee approval and obtaining of informed consent , 116 patients with AMI were r and omly assigned to receive a combination of valsartan and captopril or captopril alone . Non-culprit intermediate coronary atherosclerosis was assessed on intravascular ultrasound . The primary and secondary endpoints were the nominal change in percent atheroma volume ( PAV ) and percent change in lumen volume ( % ΔLV ) , respectively . The combination group had a significantly lower systolic blood pressure ( 117 vs. 125 mmHg ; P=0.02 ) and a lower plasma aldosterone level ( 56 vs. 75 pg/ml ; P=0.02 ) at follow-up . The nominal change in PAV was slightly lower in the combination group than in the ACEI group ( -1.9 vs. -0.68 % , P=0.06 ) . % ΔLV was -0.3 % in the ACEI group and was 4.3 % in the combination group ( P=0.03 ) . Logistic regression analysis showed that additional ARB therapy was independently associated with LV enlargement ( odds ratio , 2.144 ; 95 % confidence interval : 1.818 - 5.618 ; P=0.03 ) . CONCLUSIONS In this study of patients with AMI , additional ARB therapy had minimal impact on the progression of coronary atherosclerosis as compared with an ACEI alone . The combination of these 2 drugs , however , induces coronary artery enlargement OBJECTIVE To estimate 8-year health and economic outcomes of the angiotensin II receptor blocker valsartan versus the calcium channel blocker amlodipine in therapy of patients with type 2 diabetes and microalbuminuria based on clinical endpoints from a 6-month r and omized controlled clinical trial , the MicroAlbuminuria Reduction With VALsartan ( MARVAL ) study . METHODS We developed a Markov model that utilized urinary albumin excretion rate data to project patient distributions to 7 possible health states over 8 years . For each health state , we identified quality -adjustment weights ( health utilities ) and medical care costs from public sources . The model then calculated mean quality -adjusted survival , medical care costs , and cost-effectiveness ratios for each treatment arm . Treatment arms were compared with the incremental cost-effectiveness ratio . RESULTS Patients treated with valsartan gained 7 months ( mean ) per patient of quality -adjusted survival relative to patients treated with amlodipine ( 77 versus 70 months ; P<0.01 ) ; valsartan patients also incurred 32,412 dollars ( mean ) per patient lower medical costs than amlodipine patients ( 92,058 dollars versus 124,470 dollars ; P<0.01 ) . Model results were consistent for each year of analysis and robust to changes in key model parameters . CONCLUSION This research ( 1 ) extends 6-month clinical trial outcomes to an 8-year period , ( 2 ) translates health outcomes from technical clinical endpoints to quality -adjusted survival , and ( 3 ) estimates economic consequences of therapeutic outcomes . The results quantify the favorable long-term health ( i.e. , quality -adjusted survival ) and economic benefits ( i.e. , lower total medical costs ) of therapy with valsartan , an angiotensin II receptor blocker , versus amlodipine , a calcium channel blocker , in the treatment of patients with type 2 diabetes and microalbuminuria based on an extension of the results of a short-term clinical ( MARVAL ) trial . These research findings are important to the extent patients with type 2 diabetes and microalbuminuria do not receive the recommended antihypertensive agents that block the renin-angiotensin system ( angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers ) BACKGROUND It has recently been reported that the use of calcium-channel blockers for hypertension may be associated with an increased risk of cardiovascular complications . Because this issue remains controversial , we studied the incidence of such complications in patients with non-insulin-dependent diabetes mellitus and hypertension who were r and omly assigned to treatment with either the calcium-channel blocker nisoldipine or the angiotensin-converting-enzyme inhibitor enalapril as part of a larger study . METHODS The Appropriate Blood Pressure Control in Diabetes ( ABCD ) Trial is a prospect i ve , r and omized , blinded trial comparing the effects of moderate control of blood pressure ( target diastolic pressure , 80 to 89 mm Hg ) with those of intensive control of blood pressure ( diastolic pressure , 75 mm Hg ) on the incidence and progression of complications of diabetes . The study also compared nisoldipine with enalapril as a first-line antihypertensive agent in terms of the prevention and progression of complications of diabetes . In the current study , we analyzed data on a secondary end point ( the incidence of myocardial infa rct ion ) in the subgroup of patients in the ABCD Trial who had hypertension . RESULTS Analysis of the 470 patients in the trial who had hypertension ( base-line diastolic blood pressure , > or = 90 mm Hg ) showed similar control of blood pressure , blood glucose and lipid concentrations , and smoking behavior in the nisoldipine group ( 237 patients ) and the enalapril group ( 233 patients ) throughout five years of follow-up . Using a multiple logistic-regression model with adjustment for cardiac risk factors , we found that nisoldipine was associated with a higher incidence of fatal and nonfatal myocardial infa rct ions ( a total of 24 ) than enalapril ( total , 4 ) ( risk ratio , 9.5 ; 95 percent confidence interval , 2.7 to 33.8 ) . CONCLUSIONS In this population of patients with diabetes and hypertension , we found a significantly higher incidence of fatal and nonfatal myocardial infa rct ion among those assigned to therapy with the calcium-channel blocker nisoldipine than among those assigned to receive enalapril . Since our findings are based on a secondary end point , they will require confirmation Background Limitation of systemic and glomerular hypertension reduces urinary protein excretion and prevents renal function deterioration . Objective To investigate whether , in hypertensive patients with glomerulonephritis , a combination of an angiotensin converting enzyme inhibitor ( ACEI , fosinopril 20 mg/day ) with an angiotensin receptor blocker ( ARB , irbesartan 150 mg/day ) produces a more profound antiproteinuric effect than either drug alone . Methods Ten non-diabetic patients with glomerulonephritis , normal or slightly reduced but stable renal function ( creatinine clearance 40–106 ml/min ) without immunosuppression were studied . Clinical evaluations , 24 h blood pressure measurements and laboratory tests were performed as follows : ( 1 ) without medication ( baseline ) and in r and om sequence ; ( 2 ) ACEI alone ; ( 3 ) ARB alone ; and ( 4 ) combination of ACEI + ARB . Each period lasted for 6 weeks , separated by three washout periods of 4 weeks each without therapy . Results ACEI and ARB alone reduced proteinuria from 7.9 ± 7.1 to 5.3 ± 5.2 and 5.0 ± 4.9 g/24 h ( mean ± SD ) , respectively . The combination of ACEI + ARB induced a more remarkable reduction of proteinuria in every patient ( to 3.3 ± 3.7 g/24 h ) than either drug alone ( P = 0.039 by ANOVA ) . The enhanced antiproteinuric effect of the combined therapy could not be attributed to a more pronounced reduction of 24 h mean arterial pressure ( basal , 106 ± 8 ; ACEI , 97 ± 5 ; ARB , 98 ± 5 ; ACEI + ARB , 95 ± 5 mmHg ) or creatinine clearance ( basal , 77 ± 27 ; ACEI , 73 ± 31 ; ARB 80 ± 30 ; ACEI + ARB , 73 ± 32 ml/min ) . Conclusions A combination of ACEI and ARB in patients with glomerulonephritis produces a more profound decrease in proteinuria than either drug alone . This additive antiproteinuric effect is not dependent on changes in blood pressure or creatinine clearance . A long-term controlled study is required to confirm the positive effect of this treatment on the progression of renal function loss Microalbuminuria is a strong , consistent and independent risk factor for cardiovascular and renal disease in patients with diabetes and /or hypertension and in the general population . Several r and omized trials have shown the efficacy of inhibiting the renin-angiotensin system ( RAS ) with angiotensin-converting enzyme inhibitors ( ACEIs ) and angiotensin II receptor blockers ( ARBs ) to prevent cardiovascular events and the progression of kidney disease . These 2 classes of drugs are equally effective for renal outcomes in patients with diabetic nephropathy , but only ACEIs have been found to significantly impact the risk of all-cause mortality , predominantly cardiovascular , in patients with diabetic nephropathy . Studies on the cardiorenal efficacy of combined therapy with ACEIs and ARBs in individuals with microalbuminuria or macroalbuminuria and other cardiovascular risk factors have been inconclusive . The Long-term Impact of RAS Inhibition on Cardiorenal Outcomes ( LIRICO ) study aims to address existing questions in this setting . This is a phase III , r and omized , comparative , pragmatic trial with prospect i ve r and omized open blinded endpoint ( PROBE ) design . It will evaluate the comparative efficacy of combined therapy with ACEIs and ARBs versus monotherapy with either ACEIs or ARBs in improving cardiovascular and renal outcomes in microalbuminuric or macroalbuminuric individuals at cardiorenal risk . The study will enroll 2,100 patients , selected in a network of internal medicine , diabetology or nephrology outpatient clinics . Patients will be r and omly allocated to ACEIs , ARBs or their combination . The study has been approved and funded by the Agenzia Italiana del Farmaco ( A.I.F.A. ) within the 2005 funding plan for independent research on drugs & NA;Sleep blood pressure ( BP ) , which is partly determined by salt sensitivity and intake , is an important cardiovascular risk in hypertensives . However , there have been no studies on age-related differences in the sleep BP – lowering effect between angiotensin II receptor blockers and calcium channel blockers in Asians .  Azilsartan Circadian and Sleep Pressure — the 1st Study was a multicenter , r and omized , open-label , 2-parallel-group study conducted to compare the efficacy of 8-week oral treatment with an angiotensin II receptor blocker ( azilsartan 20 mg ) or a calcium channel blocker ( amlodipine 5 mg ) on sleep BP as evaluated by ambulatory BP monitoring . Among the overall population , amlodipine treatment achieved significantly greater reduction in sleep BP , awake BP , and 24-hour BP than azilsartan treatment . BP reduction by amlodipine was particularly pronounced in elderly hypertensive patients aged ≥60 years old . Among patients ≥60 years old , the amlodipine group had numerically , but not significantly , higher control rate of sleep BP compared with the azilsartan group . Similar results were found for awake BP and 24-hour BP . These results suggest a greater BP reduction/control by amlodipine compared with azilsartan and that reduction/control of BP by amlodipine was also more effective in the elderly population . As recommended in the American Society of Hypertension/The international Society of Hypertension and the National Institute for Health and Clinical Excellence guidelines for differentiating treatment according to age , amlodipine should be one of the options for starting treatment in the elderly population . Clinical Trial URL — http:// clinical trials.gov/show/NCT01762501 Clinical Trial ID — Approximately 40 % of Japanese patients with essential hypertension , including low-renin hypertension , are inadequately managed . Low-renin hypertension generally responds poorly to angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers , but may respond more optimally to diuretics , calcium channel blockers , and aldosterone blockers . This multicenter , r and omized , double-blind , placebo-controlled , parallel-group , dose-ranging study evaluated the efficacy and safety of the selective aldosterone blocker eplerenone in 193 Japanese patients with essential hypertension . Although not a study inclusion criterion , baseline active plasma renin levels were consistently low ( 5.7 - 10.1 mU/L ) ; most patients met the criteria for low-renin hypertension ( < or = 42.5 mU/L ; normal range , 7 - 76 mU/L ) . Patients received placebo or eplerenone 50 , 100 , or 200 mg once daily for 8 weeks . Systolic blood pressure decreased significantly ( -6.8 to -10.6 mm Hg vs. -2.1 mm Hg ; p < or = 0.0022 vs. placebo ) . Eplerenone offers significant blood pressure reduction with good tolerability in Japanese patients with hypertension , including those with low-renin hypertension OBJECTIVES We sought to evaluate approaches used to control rate , the effectiveness of rate control , and switches from one drug class to another in the Atrial Fibrillation Follow-up Investigation of Rhythm Management ( AFFIRM ) study . BACKGROUND The AFFIRM study showed that atrial fibrillation ( AF ) can be treated effectively with rate control and anticoagulation , but drug efficacy to control rate remains uncertain . METHODS Patients ( n = 2,027 ) r and omized to rate control in the AFFIRM study were given rate-controlling drugs by their treating physicians . St and ardized rate-control efficacy criteria developed a priori included resting heart rate and 6-min walk tests and /or ambulatory electrocardiographic results . RESULTS Average follow-up was 3.5 + /- 1.3 years . Initial treatment included a beta-adrenergic blocker ( beta-blocker ) alone in 24 % , a calcium channel blocker alone in 17 % , digoxin alone in 16 % , a beta-blocker and digoxin in 14 % , or a calcium channel blocker and digoxin in 14 % of patients . Overall rate control was achieved in 70 % of patients given beta-blockers as the first drug ( with or without digoxin ) , 54 % with calcium channel blockers ( with or without digoxin ) , and 58 % with digoxin alone . Adequate overall rate control was achieved in 58 % of patients with the first drug or combination . Multivariate analysis revealed an association between first drug class and several clinical variables . There were more changes to beta-blockers than to the other two-drug classes ( p < 0.0001 ) . CONCLUSIONS Rate control in AF is possible in the majority of patients with AF . Beta-blockers were the most effective drugs . To achieve the goal of adequate rate control in all patients , frequent medication changes and drug combinations were needed Objective To investigate whether angiotensin receptor blockers protect against  Alzheimer ’s disease and dementia or reduce the progression of both diseases . Design Prospect i ve cohort analysis . Setting Administrative data base of the US Veteran Affairs , 2002 - 6 . Population 819 491 predominantly male participants ( 98 % ) aged 65 or more with cardiovascular disease . Main outcome measures Time to incident Alzheimer ’s disease or dementia in three cohorts ( angiotensin receptor blockers , lisinopril , and other cardiovascular drugs , the “ cardiovascular comparator ” ) over a four year period ( fiscal years 2003 - 6 ) using Cox proportional hazard models with adjustments for age , diabetes , stroke , and cardiovascular disease . Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer ’s disease or dementia . Results Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 ( 95 % confidence interval 0.69 to 0.84 ) compared with the cardiovascular comparator and 0.81 ( 0.73 to 0.90 ) compared with the lisinopril group . Compared with the cardiovascular comparator , angiotensin receptor blockers in patients with pre-existing Alzheimer ’s disease were associated with a significantly lower risk of admission to a nursing home ( 0.51 , 0.36 to 0.72 ) and death ( 0.83 , 0.71 to 0.97 ) . Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors . This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia ( 0.54 , 0.51 to 0.57 ) and admission to a nursing home ( 0.33 , 0.22 to 0.49 ) . Minor differences were shown in mean systolic and diastolic blood pressures between the groups . Similar results were observed for Alzheimer ’s disease . Conclusions Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer ’s disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population BACKGROUND ACE inhibitors may not adequately suppress deleterious levels of angiotensin II in patients with heart failure . An angiotensin receptor blocker added to an ACE inhibitor may exert additional beneficial effects . METHODS AND RESULTS Eighty-three symptomatic stable patients with chronic heart failure receiving long-term ACE inhibitor therapy were r and omly assigned to double-blind treatment with valsartan 80 mg BID , valsartan 160 mg BID , or placebo while receiving their usual ACE inhibitor therapy . Studies were performed before and after the first dose of the test drug and again after 4 weeks of therapy . A single dose of lisinopril was administered during study days to ensure sustained ACE inhibition . Compared with placebo , the first dose of valsartan 160 mg result ed in a significantly greater reduction in pulmonary capillary wedge pressure at 3 , 4 , and 8 hours and during the prespecified 4- to 8-hour interval after the dose and in systolic blood pressure at 2 , 3 , 6 , 8 , and 12 hours and 4 to 8 hours after the dose . A pressure reduction from valsartan 80 mg did not achieve statistical significance . After 4 weeks of therapy , net reductions in 0-hour trough pulmonary capillary wedge pressure ( -4.3 mm Hg ; P=0 . 16 ) , pulmonary artery diastolic pressure ( -4.7 mm Hg ; P=0.013 ) , and systolic blood pressure ( -6.8 mm Hg ; P=0.013 ) were observed in the valsartan 160 mg group compared with placebo . After 4 weeks of therapy , plasma aldosterone was reduced by valsartan 80 mg BID ( -52 . 1 pg/mL ; P=0.001 ) and 160 mg BID ( -47.8 pg/mL ; P<0.001 ) compared with placebo , and there was a trend for a reduction in plasma norepinephrine ( -97 pg/mL ; P=0.10 ) . Seventy-four of the 83 patients completed the trial . CONCLUSIONS Physiologically active levels of angiotensin II persist during st and ard long-term ACE inhibitor therapy The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) , sponsored by the National Heart , Lung , and Blood Institute ( NHLBI ) , is the largest outcome trial of antihypertensive treatment ever carried out and the only large blood pressure ( BP ) trial to be carried out in a US population in the past decade.1 The rationale for ALLHAT , which was design ed in the early 1990s , was the urgent need to determine which of the several classes of antihypertensive drugs that had been developed and released for clinical use was most effective in preventing coronary heart disease ( CHD ) , defined as fatal CHD and nonfatal myocardial infa rct ion.2 The only r and omized trials that had previously compared representatives of the antihypertensive drug classes , the Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents3 and the Treatment of Mild Hypertension Study (TOMHS),4 showed BP reductions with all classes but were not powered to evaluate CHD outcomes . Further , prior outcome trials had shown that the reduction in CHD event rates with antihypertensive treatment was less than expected based on epidemiologic data .5 Adverse effects of study drugs , particularly diuretics , including hypokalemia , hypomagnesemia , hyperuricemia , hyperlipidemia , insulin resistance , and ventricular ectopic activity , had been adduced to account for the disappointing outcomes of earlier trials by off setting the beneficial effects of BP reduction.6,7 To further complicate the picture , benefits beyond BP reduction had been attributed to some antihypertensive drug classes , ie , improved survival and reduced morbidity in persons with heart failure or left ventricular dysfunction treated with angiotensin-converting enzyme ( ACE ) inhibitors8–10 and improved insulin sensitivity and lipid profiles with α-blocker treatment.11 In contrast , another antihypertensive drug class , the dihydropyridine calcium channel blockers ( CCBs ) , had been associated with unfavorable outcomes in patients with acute myocardial infa rct ion or unstable angina.12 There were no data Little is known about the patterns of treatment and adequacy of blood pressure control in older women . The Women ’s Health Initiative , a 40-center national study of risk factors and prevention of heart disease , breast and colorectal cancer , and osteoporosis in postmenopausal women , provides a unique opportunity to examine these issues in the largest , multiethnic , best-characterized such cohort . Baseline data from the initial 98 705 women , aged 50 to 79 years , enrolled were analyzed to relate prevalence , treatment , and control of hypertension to demographic , clinical , and risk-factor covariates , and logistic regression analyses were performed to estimate odds ratios after adjusting for multiple potential confounders . Overall , 37.8 % of the women had hypertension , which is defined as systolic blood pressure ≥140 mm Hg and /or diastolic blood pressure ≥90 mm Hg or being on medication for high blood pressure ; 64.3 % were treated with drugs , and blood pressure was controlled in only 36.1 % of the hypertensive women , with lower rates of control in the oldest group . After adjustment for multiple covariates , current hormone users had higher prevalence than did nonusers ( odds ratio 1.25 ) . Hypertensive women had more comorbid conditions than did nonhypertensive women , and women with comorbidities were more likely to be treated pharmacologically . Diuretics were used by 44.3 % of hypertensives either as monotherapy or in combination with other drug classes . As monotherapy ,  calcium channel blockers were used in 16 % , angiotensin-converting enzyme inhibitors in 14 % , & bgr;-blockers in 9 % , and diuretics in 14 % of the hypertensive women . Diuretics as monotherapy were associated with better blood pressure control than any of the other drug classes as monotherapy . In conclusion , hypertension in older women is not being treated aggressively enough because a large proportion , especially those most at risk for stroke and heart disease by virtue of age , does not have sufficient blood pressure control Background The benefits of treating hypertension in elderly diabetic patients , in terms of achieving reductions in cardiovascular morbidity and mortality , have been documented in several recent prospect i ve trials . There has , however , been some controversy regarding the effect of different antihypertensive drugs on the frequency of myocardial infa rct ion in this group of patients . Design STOP Hypertension-2 was a prospect i ve , r and omized , open trial with blinded endpoint evaluation . Methods We studied 6614 elderly patients aged 70–84 years ; 719 of them had diabetes mellitus at the start of the study ( mean age 75.8 years ) . Patients were r and omly assigned to one of three treatment strategies : conventional antihypertensive drugs ( diuretics or β-blockers ) , calcium antagonists , or angiotensin converting enzyme ( ACE ) inhibitors . Results Reduction in blood pressure was similar in the three treatment groups of diabetics . The prevention of cardiovascular mortality was also similar ; the frequency of this primary endpoint did not differ significantly between the three groups . There were , however , significantly fewer ( P = 0.025 ) myocardial infa rct ions during ACE inhibitor treatment ( n = 17 ) than during calcium antagonist treatment ( n = 32 ; relative risk 0.51 , 95 % confidence interval 0.28–0.92 ) ; but a ( non-significant ) tendency to more strokes during ACE inhibitor treatment ( n = 34 compared with n = 29 ; relative risk 1.16 , 95 % confidence interval 0.71–1.91 ) . Conclusion Treatment of hypertensive diabetic patients with conventional antihypertensive drugs ( diuretics , β-blockers , or both ) seemed to be as effective as treatment with newer drugs such as calcium antagonists or ACE inhibitors OBJECTIVE To demonstrate the utilization of a clinical improvement program in stable coronary artery disease patients to increase the evidence -proven treatment utilization , and to describe the ongoing clinical practice and lifestyle change counseling . METHODS Cross-sectional study followed by a longitudinal component in which the tools utilization to improve clinical practice was assessed by means of additional cross-sectional data collection . 710 consecutive patients were included ( Phase 1 ) . After tools implementation , within 6 months period , 705 patients were included ( Phase 2 ) for comparative analysis . R and omly , 318 patients from Phase 1 were selected , 6 - 12 months after the first evaluation ( Phase 3 ) . RESULTS Phase 1 to Phase 2 : there were improvement on smoking cessation ( P=0.019 ) , dyslipidemia ( P<0.001 ) , hypertension and physical activity ( P<0.001 ) . There was significant difference on angiotensin converting enzyme inhibitors - ACEI ( 67.2 % vs. 56.8 % , P<0.001 ) ; angiotensin II receptor blockers - ARB II ( 25.4 % vs. 32.9 % , P=0.002 ) and beta-blocker ( 88.7 % vs. 91.9 % , P=0.047 ) . Phase 1 to Phase 3 : there was both weight ( P=0.044 ) , and blood pressure reduction ( P<0.001 ) . There was statistical significant difference on ACEI ( 64.8 % vs. 61.6 % , P=0.011 ) and ARB II ( 27.0 % vs. 31.3 % , P=0.035 ) . CONCLUSION There was no significant change on the evidence -based pharmacological treatment utilization between pre and post-intervention phases ; there was significant improvement concerning smoking and physical activity in phase 2 ; substantial improvement on blood pressure levels in both comparisons ( Phase 1 to 2 and Phase 1 to 3 ) . The inclusion of a case-manager for the process management was crucial for program efficacy . Comprehensive programs for clinical practice should be pursued for longer follow-up period Hypertension is a major risk factor for cardiovascular and cerebrovascular events , and most patients with hypertension are administered antihypertensive drugs . However , not all patients achieve normal blood pressure levels . The new angiotensin receptor blocker azilsartan ( Takeda Pharmaceutical Company Limited , Osaka , Japan ) has been reported to have a strong hypotensive effect . Our study investigated the efficacy of azilsartan compared with other angiotensin receptor blockers . This study included 17 hypertensive patients on HD , who had been administered angiotensin receptor blockers , except for azilsartan , for more than 6 months before enrolling , and after enrollment , they were switched to azilsartan .  Blood tests , Holter electrocardiogram , ambulatory blood pressure monitoring , and echocardiography  were performed at baseline and at the 6-month follow-up . The blood pressure from baseline to 6 months had significantly decreased ( 24-h systolic blood pressure from 150.9 ± 16.2 mm Hg to 131.3 ± 21.7 mm Hg , P = 0.008 ) , awakening time systolic blood pressure from 152.1 ± 16.9 mm Hg to 131.7 ± 23.2 mm Hg , P = 0.01 , sleep-time systolic blood pressure from 148.1 ± 19.7 mm Hg to 130.0 ± 20.1 mm Hg , P = 0.005 ) . There was a significant reduction in serum noradrenaline levels as well as left ventricular mass index after switching to azilsartan ( from 550.1 ± 282.9 pg/mL , to 351.7 ± 152.3 pg/mL , P = 0.002 ; from 117.0 ± 26.4 g/m(2 ) to 111.3 ± 23.9 g/m(2 ) , P = 0.01 , respectively ) . Azilsartan had a significantly stronger hypotensive effect than other angiotensin receptor blockers . Thus , the switch to azilsartan might improve prognosis of hemodialysis patients . We suggest that the strong anti-hypertensive effect of azilsartan originated from a combination of primary angiotensin receptor blocker class-effect and a stronger suppression of sympathetic nervous system To determine the nature of the result ant effect on blood pressure when angiotensin converting enzyme ( ACE ) inhibitors are combined with other hypotensive agents in the treatment of uncomplicated essential hypertension , two r and omized , double-blind , crossover trials were conducted . In each trial there were four treatment phases , each 4 weeks in duration , comprising a 2 X 2 factorial experiment . Twenty-one patients completed the first study in which the effects of enalapril ( 10 mg twice daily ) were compared with hydrochlorothiazide ( 25 mg twice daily ) , with the two drugs in combination and with placebo . All blood pressure parameters were reduced in the three active treatment phases compared with placebo ( P less than 0.001 ) . Enalapril and hydrochlorothiazide were equally effective and in combination their hypotensive effects were fully additive . Sixteen patients completed the second study which compared the effects of enalapril ( 20 mg daily ) , atenolol ( 50 mg daily ) , the two drugs in combination and placebo . All blood pressure parameters were again reduced in all phases compared with placebo ( P less than 0.001 ) . Enalapril and atenolol were also equally effective , but in combination their hypotensive effects were less than fully additive , with attenuation of the potential additive response by 30 - 50 % . These results indicate that a diuretic-ACE inhibitor combination can be expected to have a greater hypotensive effect than a beta-blocker-ACE inhibitor combination . Both hydrochlorothiazide and atenolol increased plasma atrial natriuretic peptide ( ANP ) concentrations ( P less than 0.01 ) , suggesting that ANP could contribute to the hypotensive effects of these two drug classes BACKGROUND Thiazides are recommended to initiate antihypertensive drug treatment in black subjects . OBJECTIVE To test the efficacy of this recommendation in a South African black cohort . METHODS Men and women ( N = 409 ) , aged 18 to 70 years , with a mean ambulatory daytime diastolic blood pressure between 90 and 114 mm Hg , were r and omized to 13 months of open-label treatment starting with the nifedipine gastrointestinal therapeutic system ( 30 mg/d , n = 233 ) , sustained-release verapamil hydrochloride ( 240 mg/d , n = 58 ) , hydrochlorothiazide ( 12.5 mg/d , n = 58 ) , or enalapril maleate ( 10 mg/d , n = 60 ) . If the target of reducing daytime diastolic blood pressure below 90 mm Hg was not attained , the first-line drugs were titrated up and after 2 months other medications were added to the regimen . RESULTS While receiving monotherapy ( 2 months , n = 366 ) , the patients ' systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg for nifedipine , 17/11 mm Hg for verapamil , 12/8 mm Hg for hydrochlorothiazide , and 5/3 mm Hg for enalapril . At 2 months the blood pressure of more patients treated with nifedipine was controlled : 133 ( 63.3 % , P</=.03 ) vs 20 ( 39.9 % ) receiving verapamil , 21 ( 40.4 % ) receiving hydrochlorothiazide , and 11 ( 20.8 % ) receiving enalapril . At 13 months ( n = 257 ) , more patients ( P<.001 ) continued receiving monotherapy with nifedipine ( 94/154 [ 61.0 % ] ) or verapamil ( 22/35 [ 62.9 % ] ) than hydrochlorothiazide ( 10/39 [ 25.6 % ] ) or enalapril ( 1/29 [ 3.4 % ] ) . A sustained decrease of left ventricular mass ( P<.001 ) with no between-group differences was achieved at 4 and 13 months . CONCLUSIONS In contrast to current recommendations , calcium channel blockers are more effective than thiazides as initial treatment in black subjects with hypertension . If treatment is started with thiazides or converting-enzyme inhibitors , combination therapy is more likely to be required to control blood pressure and reduce left ventricular mass Drug therapy often fails to control hypertension . Azilsartan medoxomil ( AZL-M ) is a newly developed angiotensin II receptor blocker with high efficacy and good tolerability . This double-blind , controlled , r and omised trial compared its antihypertensive efficacy and safety vs the angiotensin-converting enzyme inhibitor ramipril ( RAM ) in patients with clinic systolic blood pressure ( SBP ) 150–180 mm Hg . Patients were r and omised ( n=884 ) to 20 mg AZL-M or 2.5 mg RAM once daily for 2 weeks , then force-titrated to 40 or 80 mg AZL-M or 10 mg RAM for 22 weeks . The primary endpoint was change in trough , seated , clinic SBP .  Mean patient age was 57±11 years , 52.4 % were male , 99.5 % were Caucasian . Mean baseline BP was 161.1±7.9/94.9±9.0 mm Hg . Clinic SBP decreased by 20.6±0.95 and 21.2±0.95 mm Hg with AZL-M 40 and 80 mg vs12.2±0.95 mm Hg with RAM ( P<0.001 for both AZL-M doses ) . Adverse events leading to discontinuation were less frequent with AZL-M 40 and 80 mg ( 2.4 % and 3.1 % , respectively ) than with RAM ( 4.8 % ) . These data demonstrated that treatment of stage 1–2 hypertension with AZL-M was more effective than RAM and better tolerated BACKGROUND In patients with symptomatic congestive heart failure receiving optimal therapy with an angiotensin-converting enzyme ( ACE ) inhibitor and a beta-blocker , the impact of using an angiotensin receptor blocker on submaximal exercise capacity and on neurohumoral activation at rest and during stress has not been investigated . METHODS Thirty-three patients with congestive heart failure , New York Heart Association II or III symptoms , and left ventricular ejection fraction 25.5 % + /- 7.2 % treated with an ACE inhibitor and a beta-blocker were recruited . Patients were r and omly assigned to receive irbesartan 150 mg per day ( n = 22 ) or a placebo ( n = 11 ) for 6 months . Maximal exercise capacity was assessed using a ramp protocol .  Submaximal exercise duration was assessed using a constant load protocol , and plasma norepinephrine and angiotensin II ( A-II ) were measured in resting state , at 6 minutes , and at peak exercise . RESULTS Patients treated with irbesartan presented a 26 % increase in submaximal exercise time ( + 281 seconds , P = .08 ) whereas exercise duration increased by only 7 % in patients treated with a placebo ( + 128 seconds , P = NS irbesartan vs placebo ) . Norepinephrine levels increased to a similar extent in both groups , whereas A-II levels did not increase or change in response to therapy . CONCLUSIONS Dual A-II suppression with an ACE inhibitor plus irbesartan provides a small but a significant increase in submaximal exercise capacity . This beneficial effect is observed despite no significant changes in maximal exercise capacity , and in resting or exercise-induced increase in neurohumoral activation INTRODUCTION Ablation has emerged as a major treatment option for atrial fibrillation ( AF ) . However , this procedure is limited by a significant rate of AF recurrence . We aim ed to examine the effects of statins , angiotensin-converting enzyme inhibitors ( ACE-I ) , and angiotensin receptor blockers ( ARB ) on the recurrence rate of AF following ablation . METHODS We conducted a retrospective study of 177 consecutive patients ( mean age = 56 + /- 11 yrs , 69 % males ) who underwent ablation for paroxysmal ( n = 132 ) or persistent AF ( n = 45 ) . Patients were treated with ACE-I ( n = 31 ) or ARB ( n = 18 ) or statins ( n = 50 ) prior to ablation and for the duration of follow-up . RESULTS After a mean follow-up of 13.8 + /- 8.6 months , 72 % of patients were free of AF . For patients taking statins , 33 of 50 ( 60 % ) were free of AF . In patients treated with ACE-I , 17 of 31 ( 55 % ) were free from AF , while in the group of patients treated with ARB , 17 of 18 ( 94 % ) were free from AF . Using Cox regression analysis to correct for baseline variables , treatment with statins did not decrease the recurrence rate ( HR = 1.10 [ 95 % CI : 0.55 - 2.27 ] p = 0.79 ) ; nor did treatment with renin angiotensin system ( RAS ) blockers ( HR 0.94 [ 95 % CI : 0.46 - 1.93 ] p = 0.87 ) . However , subgroup analysis showed that treatment with ARB was associated with a trend towards lower AF recurrence [ HR 0.17 , ( 95 % CI : 0.02 - 1.34 ) p = 0.09 ] . CONCLUSIONS Even though statins and RAS blockers possess anti-inflammatory properties , they did not decrease the recurrence of AF following ablation . However , the subset of patients taking ARB exhibited a trend towards lower AF recurrence . Larger , r and omized studies are needed to address this observation Objective : To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension Objective It has yet to be determined whether genotyping at the angiotensin-converting enzyme ( ACE ) locus is predictive of blood pressure response to an ACE inhibitor . Methods Participants from the African American Study of Kidney Disease and Hypertension trial r and omized to the ACE inhibitor ramipril ( n = 347 ) were genotyped at three polymorphisms on ACE , just downstream from the ACE insertion/deletion polymorphism ( Ins/Del ) : G12269A , C17888 T , and G20037A . Time to reach target mean arterial pressure ( ≤107 mmHg ) was analyzed by genotype and ACE haplotype using Kaplan – Meier survival curves and Cox proportional hazard models . Results Individuals with a homozygous genotype at G12269A responded significantly faster than those with a heterozygous genotype ; the adjusted ( average number of medications and baseline mean arterial pressure ) hazard ratio ( homozygous compared to heterozygous genotype ) was 1.86 ( 95 % confidence limits 1.32–3.23 ; P < 0.001 for G12269A genotype ) . The adjusted hazard ratio for participants with homozygous ACE haplotypes compared to those heterozygous ACE haplotypes was 1.40 ( 1.13–1.75 ; P = 0.003 for haplotype ) . The ACE genotype effects were specific for ACE inhibition ( i.e. , not seen among those r and omized to a calcium channel blocker ) , and were independent of population stratification . Conclusions African-Americans with a homozygous genotype at G12269A or homozygous ACE haplotypes  responded to ramipril significantly faster than those with a heterozygous genotype or heterozygous haplotypes , suggesting that heterosis may be an important determinant of responsiveness to an ACE inhibitor . These associations may be a result of biological activity of this polymorphism , or of linkage disequilibrium with nearby variants such as the ACE Ins/Del , perhaps in the regulation of ACE splicing BACKGROUND Treatment of hypertension with diuretics , beta-blockers , or both leads to improved outcomes . It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone . We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme ( ACE ) inhibitors with the outcomes in those treated with diuretic agents . METHODS We conducted a prospect i ve , r and omized , open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practice s. Subjects were followed for a median of 4.1 years , and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models . RESULTS At base line , the treatment groups were well matched in terms of age , sex , and blood pressure . By the end of the study , blood pressure had decreased to a similar extent in both groups ( a decrease of 26/12 mm Hg ) . There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group ( 56.1 per 1000 patient-years ) and 736 cardiovascular events or deaths from any cause in the diuretic group ( 59.8 per 1000 patient-years ; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [ 95 percent confidence interval , 0.79 to 1.00 ] ; P=0.05 ) . Among male subjects , the hazard ratio was 0.83 ( 95 percent confidence interval , 0.71 to 0.97 ; P=0.02 ) ; among female subjects , the hazard ratio was 1.00 ( 95 percent confidence interval , 0.83 to 1.21 ; P=0.98 ) ; the P value for the interaction between sex and treatment-group assignment was 0.15 . The rates of nonfatal cardiovascular events and myocardial infa rct ions decreased with ACE-inhibitor treatment , whereas a similar number of strokes occurred in each group ( although there were more fatal strokes in the ACE-inhibitor group ) . CONCLUSIONS Initiation of antihypertensive treatment involving ACE inhibitors in older subjects , particularly men , appears to lead to better outcomes than treatment with diuretic agents , despite similar reductions of blood pressure Objectives To determine whether polymorphisms in the renin – angiotensin system can predict blood pressure-lowering response to antihypertensive treatment ; more specifically , in response to treatment with irbesartan or atenolol . Design and methods Eighty-six patients with hypertension were r and omized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the β1 adrenergic receptor blocker atenolol and followed for 3 months . We analysed angiotensinogen T174 M and M235 T , angiotensin converting enzyme ( ACE ) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction . Results The mean reductions in blood pressure were similar for both treatments . In the irbesartan group , individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure , exceeding those with the D allele ( − 18 ± 11 SD versus − 7 ± 10 mmHg , P = 0.0096 ) . This was not the case during treatment  with atenolol  , and the interaction term between type of treatment and ACE II genotype was significant ( P = 0.0176 ) . The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment . Conclusions ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol . Thus , specific genotypes might predict the response to specific antihypertensive treatment AIMS To assess physicians ' adherence to guideline -recommended medications for the treatment of chronic heart failure ( CHF ) with reduced ejection fraction . METHODS AND RESULTS QUALIFY is an international prospect i ve observational longitudinal survey of 7092 CHF out patients recruited 1 - 15 months after hospitalization for heart failure from September 2013 to December 2014 in 547 centres in 36 countries . We constructed a five-class guideline adherence score for angiotensin converting enzyme inhibitors ( ACEIs ) , beta-blockers , angiotensin receptor blockers ( ARBs ) , mineralocorticoid receptor antagonists , and ivabradine . The adherence score was good in 67 % , moderate in 25 % , and poor in 8 % of patients . Adherence was lower in women than men but there were differences in age ( 65.7 ± 12.5 years women vs. 62.2 ± 12.4 years men , P < 0.001 ) and the proportion of women at ≥50 % target dose of beta-blockers was lower in those > 67 years ( median ) ( 11 % vs. 16.2 % , P = 0.005 ) . Geographic variations were observed with lower adherence scores in Central /Eastern European countries . The proportion of patients at target dose and ≥50 % of target dose was low ( 27.9 % and 63.3 % for ACEIs , 14.8 % and 51.8 % for beta-blockers , 6.9 % and 39.5 % for ARBs , and 6.9 % and 39.5 % for ivabradine , respectively ) . It was also lower in patients most recently hospitalized ( < 6 vs. ≥6 months ) except for beta-blockers . CONCLUSION This international survey shows that adherence to guideline -recommended medications is relatively satisfactory but the dosage of recommended CHF medications is usually suboptimal . Action plans aim ed at improving adherence to guidelines are required Increases in the cardiovascular risk marker microalbuminuria are attenuated by blood pressure reduction using blockers of the renin-angiotensin system . Such changes in microalbuminuria have not been observed when beta-blockers are used . A prespecified secondary end point of the Glycemic Effects in Diabetes Mellitus Carvedilol-Metoprolol Comparison in Hypertensives ( GEMINI ) trial was to examine the effects of different beta-blockers on changes in albuminuria in the presence of renin-angiotensin system blockade . Participants with hypertension and type 2 diabetes were r and omized to either metoprolol tartrate ( n=737 ) or carvedilol ( n=498 ) in blinded fashion after a washout period of all antihypertensive agents except for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers . Blinded medication was titrated to achieve target blood pressure , with a-5 month follow-up period . The current analysis examined microalbuminuria , using spot urine albumin : creatinine , in participants who had values at screening and trial end . A greater reduction in microalbuminuria was observed for those r and omized to carvedilol ( -16.2%Delta ; 95 % confidence interval , -25.3 , -5.9 ; P=0.003 ) . Of those with normoalbuminuria at baseline , fewer progressed to microalbuminuria on carvedilol versus metoprolol ( 20 of 302 [ 6.6 % ] versus 48 of 431 [ 11.1 % ] , respectively ; P=0.03 ) . Microalbuminuria development was not related to differences in blood pressure or achievement of blood pressure goal ( 68 % carvedilol versus 67 % , metoprolol ) . Presence of metabolic syndrome at baseline was the only independent predictor of worsening albuminuria throughout the study ( P=0.004 ) . Beta-blockers have differential effects on microalbuminuria in the presence of renin-angiotensin system blockade . These differences can not be explained by effects on blood pressure or alpha1-antagonism but may relate to antioxidant properties of carvedilol
First-line low-dose thiazides reduce all morbidity and mortality outcomes .
First-line ACE inhibitors and calcium channel blockers may be similarly effective but the evidence is less robust .
First-line high-dose thiazides and first-line beta-blockers are inferior to first-line low-dose thiazides
BACKGROUND Sustained elevated blood pressure , unresponsive to lifestyle measures , leads to a critically important clinical question : What class of drug to use first-line ?
This review answers that question .
OBJECTIVES PRIMARY OBJECTIVE To quantify the benefits and harms of the major first-line anti-hypertensive drug classes : thiazides , beta-blockers , calcium channel blockers , angiotensin converting enzyme ( ACE ) inhibitors , alpha-blockers , and angiotensin II receptor blockers ( ARB ) .