A prospective evaluation of persistence on antihypertensive treatment with different antihypertensive drugs in clinical practice South African hypertension guideline 2011. 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 Combinations of olmesartan and a calcium channel blocker or a diuretic in elderly hypertensive patients: a randomized, controlled trial1 Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study. Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): Practical Implications Tolerability of antihypertensive drugs in a community-based setting. 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 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 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 Efficacy of Combination Antihypertensive Therapy with Low-Dose Indapamide: Assessment by Blood Pressure Self-Monitoring at Home Use of calcium channel blockers is associated with better cognitive performance in older hypertensive patients with subjective memory complaints Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy. Calcium-channel blockers and cognitive function in elderly people: results from the Canadian Study of Health and Aging. Persistence with antihypertensive medication: Australia-wide experience, 2004-2006. A Comparative Study of the Management of Stage 2 hypertension by Combined therapy with Losartan, Amlodipine and Hydrochlorothiazide Calcium channel blockers and cardiac mortality in the treatment of hypertension: a report from the Department of Health Hypertension Care Computing Project (DHCCP) Preferable effects of olmesartan/calcium channel blocker to olmesartan/diuretic on blood pressure variability in very elderly hypertension: COLM study subanalysis Prevention of cardiovascular events with calcium channel blocker-based combination therapies in patients with hypertension: a randomized controlled trial The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. Calcium-Channel Blockers and Dementia Risk in Older Adults　- National Health Insurance Service - Senior Cohort (2002-2013). Comparative study of high dose mono-therapy of amlodipine or telmisartan, and their low dose combination in mild to moderate hypertension. Angiotensin-converting enzyme inhibitors, calcium channel blockers, and breast cancer. Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension Bedtime administration of cilnidipine controls morning hypertension. Concomitant administration of clopidogrel with statins or calcium-channel blockers: insights from the TRITON-TIMI 38 (trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38). Effect of dihydropyridine calcium channel blockers and glucocorticoids on the prevention and development of scleroderma renal crisis in an Italian case series. 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 Medical treatment of hypertension in Switzerland. The 2009 Swiss Hypertension Survey (SWISSHYPE). A computerized intervention to decrease the use of calcium channel blockers in hypertension Tianma Gouteng Yin as Adjunctive Treatment for Essential Hypertension: A Systematic Review of Randomized Controlled Trials Calcium Channel Blockade and Preservation of Renal Graft Function in Cyclosporine-Treated Recipients: A Prospective Randomized Placebo-Controlled 2-Year Study The risk of myocardial infarction associated with antihypertensive drug therapies. Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial Combined influence of proton-pump inhibitors, calcium-channel blockers and CYP2C19*2 on on-treatment platelet reactivity and on the occurrence of atherothrombotic events after percutaneous coronary intervention. Risk of hyperkalemia in nondiabetic patients with chronic kidney disease receiving antihypertensive therapy. Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension. Comparative effects of mibefradil and nifedipine gastrointestinal transport system on autonomic function in patients with mild to moderate essential hypertension The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Dementia risk with antihypertensive use and blood pressure variability The effects of increasing calcium channel blocker dose vs. adding a diuretic to treatment regimens for patients with uncontrolled hypertension Appropriate Blood Pressure Control in NIDDM (ABCD) Trial A new-generation N/L-type calcium channel blocker leads to less activation of the renin–angiotensin system compared with conventional L type calcium channel blocker Is There a Clinically Significant Interaction Between Calcium Channel Antagonists and Clopidogrel?: Results From the Clopidogrel for the Reduction of Events During Observation (CREDO) Trial Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of Aging Nifedipine or hydralazine as a first‐line agent to control hypertension in severe preeclampsia Comparative Effects of an Angiotensin II Receptor Blocker (ARB)/Diuretic vs. ARB/Calcium-Channel Blocker Combination on Uncontrolled Nocturnal Hypertension Evaluated by Information and Communication Technology-Based Nocturnal Home Blood Pressure Monitoring　- The NOCTURNE Study. Combination of antihypertensive therapy in the elderly, multicenter investigation (CAMUI) trial. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril. Risk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. Use of antihypertensive medications and breast cancer risk Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Differential effects of calcium channel blockers on size selectivity of proteinuria in diabetic glomerulopathy. Choices, persistence and adherence to antihypertensive agents: evidence from RAMQ data. Practitioner's Trial on the Efficacy of Antihypertensive Treatment in the Elderly Hypertension (The PATE-Hypertension Study) in Japan.
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 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 Objective : The aim of the present study was to compare the cardiovascular effects of olmesartan , an angiotensin II receptor blocker , combined with a calcium channel blocker ( CCB ) or a diuretic , in a prospect i ve , r and omized , open-label , blinded endpoint trial . Methods : Japanese hypertensive patients aged at least 65 to less than 85 years with SBP at least 140 mmHg and /or DBP at least 90 mmHg with antihypertensive treatment , or SBP at least 160 mmHg and /or DBP at least 100 mmHg without antihypertensive treatment were r and omized to receive olmesartan with either a dihydropyridine CCB or a low-dose diuretic . If SBP and /or DBP remained at least 140 and /or at least 90 mmHg , the other antihypertensive drug was added . The primary endpoint was a composite of fatal and nonfatal cardiovascular events . The median follow-up time was 3.3 years . Results : Blood pressure decreased similarly in both groups . The primary endpoint occurred in 116/2568 patients ( 4.5 % ) in the olmesartan plus CCB group and in 135/2573 patients ( 5.3 % ) in the olmesartan plus diuretic group [ hazard ratio 0.83 , 95 % confidence interval ( CI ) 0.65–1.07 , P = 0.16 ] . Rates of all-cause death and cardiovascular deaths were similar . Among patients aged at least 75 years , the incidence of stroke tended to be lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group ( hazard ratio 0.63 , 95 % CI 0.38–1.02 , P = 0.059 , interaction P = 0.019 ) . Fewer patients in the olmesartan plus CCB group ( 8.2 % , 211/2568 ) than in the olmesartan plus diuretic group ( 9.8 % , 253/2573 ; P = 0.046 ) experienced serious adverse events . Conclusion : Despite no significant difference in cardiovascular events , the different safety profiles suggest that the combination of olmesartan and CCB may be preferable to that of olmesartan and diuretic 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 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 BACKGROUND Outside the experimental environment of clinical trials , the tolerability of angiotensin-converting enzyme inhibitors ( ACEIs ) , calcium channel blockers ( CCBs ) , and the angiotensin II antagonist losartan has not been compared . OBJECTIVES The purpose of this study was to estimate , in current clinical practice , the 3-month cumulative incidence of side effects among first-time users of losartan , ACEIs , and CCBs for hypertension . METHODS We conducted a prospect i ve cohort study through a network of 173 pharmacies across Canada to identify patients with hypertension who were newly prescribed monotherapy with losartan , an ACEI , or a CCB .  Individuals were interviewed by telephone 3 times over a 3-month period to determine perceived side effects of the antihypertensive medication prescribed . Data were analyzed using a multivariate logistic regression model . RESULTS Among the 663 eligible individuals , the 3-month cumulative incidence of perceived side effects was 52.5 % ( 42/80 ) , 60.2 % ( 222/369 ) , and 69.6 % ( 149/214 ) for those treated with losartan , an ACEI , and a CCB , respectively . After adjustment for sex , age , level of education , number of symptoms perceived the week before entering the study , prior use of antihypertensive drugs , current use of any other drug , drug insurance coverage , and duration of hypertension , the odds of reporting a side effect were significantly higher among patients treated with an ACEI ( odds ratio [ OR ] = 1.78 : 95 % CI , 1.02 - 3.12 ) or a CCB ( OR = 2.65 ; 95 % CI , 1.47 - 4.78 ) compared with patients treated with losartan . CONCLUSIONS In a community-based setting , we observed that losartan is better tolerated than ACEIs and CCBs . Given that the occurrence of side effects may contribute to lower adherence to drug treatment , the low incidence of side effects associated with losartan makes it an attractive antihypertensive drug choice 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 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 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 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 Background Hypertension is strongly associated with cognitive decline and a promising target for dementia prevention . Our aim was to investigate the association between different antihypertensive treatments and cognitive performance in elderly hypertensive patients presenting with subjective memory complaints . Patients and methods Three hundred and seventy-eight elderly hypertensive patients more than 60 years ( mean age 70.4 ± 6.3 years ) treated with at least one antihypertensive agent and presenting with subjective memory complaints but without dementia were prospect ively recruited and underwent a combination of neuropsychological tests , brain magnetic resonance imaging with semiquantification of white matter hyperintensities , carotid echotracking , brachial endothelial function , and ambulatory blood pressure assessment s. Results None of the three composite scores ( memory score , verbal fluency , and visual memory capacity ) was found associated with blood pressure levels . On the other h and , age-adjusted and sex-adjusted analyses showed a significant and positive association between memory score and use of calcium channel blockers ( CCBs ) ( users : + 0.14 ± 0.09 versus nonusers : −0.12 ± 0.06 ; P = 0.016 ) . Multivariate analyses also revealed that CCB use was significantly associated with a better memory score , independently of age , male sex , white matter hyperintensities , and carotid wall cross-sectional area , all of which were associated with worse memory scores . Conclusion In elderly hypertensive treated patients with subjective memory complaints  , CCB use was associated with better memory performance independently of blood pressure level and macrovascular and microvascular alterations , suggesting a specific neuroprotective effect of this pharmacological class . Interventional controlled trials are required to confirm the specific protective effect of CCBs on cognitive decline 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 Concern has been raised about the potential for adverse cognitive effects associated with the use of calcium-channel blockers ( CCBs ) in older people . This study was undertaken to examine prospect ively the association between the use of these and other antihypertensive drugs and cognitive function . METHODS The authors examined data from the Canadian Study of Health and Aging ( CSHA ) , a population -based , prospect i ve 5-year investigation of the epidemiology of dementia and other health problems in Canadians 65 years of age and older . The risk of cognitive decline , as indicated by a decline in performance on the Modified Mini-Mental State ( 3MS ) examination over the 5-year period , was assessed in relation to the use of antihypertensive and diuretic drugs by 205 subjects with a history of hypertension and no evidence of dementia at baseline . RESULTS The proportion of subjects whose cognitive performance declined over the study period was significantly higher in the group using CCBs than in the group using other antihypertensive agents ( 75 % v. 59 % ) . The adjusted odds ratio ( OR ) for a significant decline in cognitive performance ( defined as a decrease in 3MS score of 10 points or more ) was 2.28 ( 95 % confidence interval [ CI ] 1.12 - 4.66 ) for subjects using CCBs . The adjusted ORs ( and 95 % CIs ) for cognitive decline in subjects using selected antihypertensive agents or diuretics relative to those exposed to beta-blockers were as follows : angiotensin-converting-enzyme inhibitor , OR 1.36 ( 95 % CI 0.41 - 4.55 ) ; diuretic or other antihypertensive drug , OR 1.45 ( 95 % CI 0.51 - 4.14 ) ; dihydropyridine CCB ( nifedipine ) , OR 1.94 ( 95 % CI 0.52 - 7.27 ) and non-dihydropyridine CCB ( diltiazem or verapamil ) , OR 3.72 ( 95 % CI 1.22 - 11.36 ) . INTERPRETATION Older people taking CCBs were significantly more likely than those using other agents to experience cognitive decline . These findings are consistent with the results of previous cross-sectional research and emphasize the need for further trials to examine the associations between CCB use , blood pressure and cognitive impairment in elderly patients OBJECTIVE To study persistence and adherence with the use of common  antihypertensive ( AHT ) medications .  DESIGN , SETTING AND PARTICIPANTS Longitudinal assessment of Pharmaceutical Benefit Scheme cl aim records covering the period January 2004 to December 2006 . We analysed a 10 % r and om sample of all Australian long-term health concession card holders who had been commenced on an angiotensin II receptor antagonist ( A2RA ) , an angiotensin-converting enzyme inhibitor ( ACEI ) and /or a calcium channel blocker ( CCB ) , but for whom no AHT medication had been dispensed in the previous 6 months . MAIN OUTCOME MEASURES Proportion of patients failing to fill a second prescription ; median persistence time with medication ( ie , non-cessation of therapy ) ; persistence with medication over 33 months ; median medication possession ratio ( MPR , defined as the proportion of prescribed medication actually consumed by patients persisting with treatment ) . RESULTS The data base yielded information relating to 48 690 patients prescribed AHT medication .  Nineteen per cent of patients failed to collect a second prescription . The median persistence time was 20 months . The data were little different from the population average with respect to A2RAs or ACEIs , but persistence was 57 % poorer with respect to CCBs ( log-rank P < 0.001 ) ( 28 % of patients prescribed CCBs failed to collect a second prescription ; median persistence time , 7 months ) . There were differences in persistence between individual drugs in the respective classes , the best outcomes being with c and esartan and  telmisartan  ( A2RAs ; 10%-20 % better ) , perindopril ( ACEI ; 25 % better ) and lercanidipine ( CCB ; 25 % better ) . Median MPRs were generally around 100 % , indicating that most patients who collected prescriptions also showed good adherence to treatment regimens . CONCLUSION There is an ongoing problem of poor persistence with commonly used AHT medications . This may represent a diminished opportunity for cardiovascular disease prevention Background The most effective and accurate treatment of hypertensive patients  reduces cardiovascular events and improves the quality of life . Objective This study compared the efficacy and safety of combined ( combination therapy ) with an angiotensin-receptor blocker ( ARB ) a calcium-channel blocker ( CCB ) ( Losartan / Amloidipine 50/10 mg ) vs maximal combination doses of ARB with hydrochlorothiazide ( Losartan /HCTZ 100/25 mg ) and maximal combination doses of CCB with HCTZ ( Amlodipine /HCTZ 10/25 mg ) in the management of stage 2 hypertension . Methods This r and omized clinical trial ( RTC ) comprised 478 hypertensive patients with mean age 50.5±5.21 years , and took place between January 2010 and December 2011 in Vasei Hospital clinic in Sabzevar . Antihypertensive drugs were washed out after 5 days of discontinuation of drugs and the patients with mean blood pressure in sitting position ≥ 160 and < 200 mmHg in systole and ≥ 100 and < 110 mmHg in diastole were r and omized into three groups : Losartan / Amlodipine 50/10 mg ( n = 164 ) , Losartan / HCTZ 100/25 mg ( n = 155 ) and Amlodipine / HCTZ 10/25 mg ( n = 159 ) . The end point was reaching the blood pressure below 140/90 within 56 days of treatment in each group . Results There was a significant difference in systolic blood pressure reductions between treatment groups ( P<0.001 ) and also there was a significant difference between groups in reducing diastolic blood pressure ( P<0.01 ) . The highest systolic and diastolic blood pressure reduction respectively was found in Amlodipine/losartane and losartane/HTCZ group . The ANCOVA analysis revealed that only treatment regimen had a significant effect ( P=0.01 ) and other factor including Age , Gender , Diabetes Mellitus , Smoking and High serum cholesterol did n’t have significant effect on blood pressure reduction . Conclusion ARB/CCB combination therapy reduced blood pressure more effectively than the maximal doses of ARB or CCB with HCTZ in stage 2 hypertensive patients within this period of study 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 Objective : The aims of this sub analysis of the COLM trial [ NCT00454662 ] were to compare visit-to-visit variability ( VVV ) of blood pressure ( BP ) between age groups and between two treatment combinations , that is , the angiotensin II receptor blocker , olmesartan combined with a calcium channel blocker ( CCB ) , or a diuretic and to investigate the effect of VVV of BP on cardiovascular events in elderly hypertensive patients . Methods : Hypertensive patients ages 65–84 years with a history of and /or risk factors for cardiovascular disease were r and omized to receive treatment with olmesartan along with either a CCB or a diuretic  for at least 3 years . This sub analysis comprised 4876 patients who had their office BP measured at least three occasions ( median nine occasions ) during the follow-up period .  VVV of BP was defined by several metrics including the within-individual st and ard deviation of every visit during the follow-up period . Results : VVV of SBP was larger in the very elderly group ( 75–84 years ) than in the elderly group ( 65–74 years ) . VVV of SBP was smaller in the olmesartan along with CCB group than in the olmesartan along with diuretic group , especially in very elderly patients and also isolated systolic hypertensive patients . The incidence rate of primary endpoint increased along with an increment in the SD of SBP in all of the age and treatment groups . Conclusion : VVV of SBP may mediate the preferable effect of combination of angiotensin II receptor blocker along with CCB on cardiovascular events in the very elderly and also isolated systolic hypertensive patients 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 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 BACKGROUND Some disagreements surround the effects of calcium-channel blockers ( CCBs ) on the risk of dementia . The purpose of this study was to investigate the protective effects of CCBs on dementia among elderly hypertensive Koreans . Methods and Results : We conducted a large population -based cohort study using the senior cohort data base of the Korean National Health Insurance Service ( 2002 - 2013 ) . Subjects were elderly hypertensive Koreans older than 60 years of age . A total of 18,423 patients ( CCB user group : 13,692 patients ; non-CCB antihypertensive user group : 4,731 patients ) were statistically analyzed using the Cox proportional hazard regression model to estimate the adjusted hazard ratio ( aHR ) and confidence intervals ( CIs ) of dementia associated with CCB use . There were 2,881 cases ( 21.0 % ) of dementia in the CCB user group and 1,124 cases ( 23.8 % ) in the non-user group . CCB use significantly reduced the risk of total dementia ( aHR 0.81 , 95 % CI 0.75 - 0.87 , P<0.0001 ) , Alzheimer 's dementia ( aHR 0.80 , 95 % CI 0.72 - 0.88 , P<0.0001 ) , and vascular dementia ( aHR 0.81 , 95 % CI 0.70 - 0.94 , P=0.0067 ) . CONCLUSIONS CCB use had a protective effect on the risk of dementia  among elderly hypertensive Koreans . ( Circ J 2016 ; 80 : 2336 - 2342 ) INTRODUCTION Hypertension is one of the major public health challenges worldwide . Angiotensin receptor blockers ( ARBs ) and Calcium channel blockers ( CCBs ) are among the first line antihypertensive drugs . However , optimal treatment strategies in mild to moderate hypertensives who failed to achieve  blood pressure ( BP ) control  with low-dose mono-therapy are not well established . This study was done to compare efficacy and safety of high dose mono-therapy of Amlodipine , Telmisartan and their low dose combination in mild to moderate hypertensives who failed to achieve BP control with low dose mono-therapy of either drug . MATERIAL S AND METHODS A total of 96 patients , fulfilling inclusion and exclusion criteria were enrolled in the study after obtaining informed consent . Patients were r and omized into three treatment groups i.e. Telmisartan 80 mg , Amlodipine 10 mg and low dose combination of Telmisartan 40 mg + Amlodipine 5 mg once daily for two months . The systolic BP , Diastolic BP , and ADRs were recorded at 0 , 2 , 4 , 8 weeks . RESULTS In the present study , significant reduction of mean systolic blood pressure ( SBP ) and mean diastolic blood pressure ( DBP ) was seen in all the three treatment groups . Low dose combination of Amlodipine 5 mg and Telmisartan 40 mg showed statistically significant reduction in SBP as compared to Telmisartan 80 mg mono-therapy and in DBP as compared to Amlodipine 10 mg mono-therapy . Maximum adverse drug reactions ( ADRs ) were reported in Amlodipine mono-therapy group , like ankle oedema , constipation , headache and fatigue . DISCUSSION AND CONCLUSION In term of BP control , low-dose combination therapy appears a better therapeutic approach than high-dose mono-therapy 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 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 Morning blood pressure ( BP ) level plays an important role in the incidence of cardiovascular disease . Recently , Kario , et al proposed the usefulness of ME difference ( morning minus evening systolic BP ) and ME average ( average of morning and evening systolic BP ) for the evaluation of antihypertensive treatment . Cilnidipine is a novel calcium channel blocker ( CCB ) that exerts inhibitory actions not only on L-type but also on N-type calcium channels . We investigated the effect of bedtime administration of cilnidipine ( 10 mg ) in addition to the antihypertensive treatment for uncontrolled morning hypertension . Twenty-three hypertensive out patients ( 13 males and 10 females ; mean age , 66.9 years ) with stable antihypertensive medication and uncontrolled morning BP were studied using self-measured BP monitoring in the morning and evening . Morning SBP ( P < 0.001 ) and DBP ( P < 0.001 ) decreased significantly from 150.2 + /- 8.7 and 87.8 + /- 9.3 to 132.7 + /- 7.4 and 77.5 + /- 8.5 mmHg , respectively , after the addition of cilnidipine .  Morning heart rate did not change ( 63.3 + /- 7.0 to 64.1 + /- 9.4 ) . The evening SBP , but not DBP , decreased significantly after treatment . Both the ME average ( P < 0.001 ) and ME difference ( P < 0.01 ) significantly decreased from 143.0 + /- 9.2 and 14.3 + /- 12.4 to 131.3 + /- 7.2 and 2.8 + /- 9.2 mmHg after treatment , respectively . The microalbuminuria decreased from 39.6 + /- 13.2 to 27.3 + /- 8.4 mg/g Cr . In conclusion , L-/N-type CCB cilnidipine may be useful for patients with uncontrollable morning hypertension  by reducing both ME average and ME difference OBJECTIVES This study sought to evaluate the clinical relevance of potential clopidogrel drug-drug interactions . BACKGROUND Some studies have demonstrated that statins and calcium-channel blockers ( CCBs ) may attenuate the pharmacodynamic effects of clopidogrel . METHODS The TRITON-TIMI 38 ( Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infa rct ion 38 ) enrolled 13,608 patients with an acute coronary syndrome ( ACS ) and planned percutaneous coronary intervention ( PCI ) , and r and omized them to clopidogrel or prasugrel . Use of a statin or CCB was left to the discretion of the treating physician . A multivariable Cox model with propensity score was employed to evaluate the association between statin or CCB use and clinical outcomes . RESULTS Of the 6,795 subjects assigned to clopidogrel , 4,794 ( 70.6 % ) were on a CYP3A4-metabolized statin , and 966 ( 14.2 % ) were on a CCB at r and omization . The risk of cardiovascular ( CV ) death , myocardial infa rct ion ( MI ) , or stroke was similar regardless of baseline use of statins ( adjusted hazard ratio [ HR ] : 1.02 , 95 % confidence interval [ CI ] : 0.85 to 1.22 ) or CCBs ( adjusted HR : 1.16 ; 95 % CI : 0.94 to 1.43 ) in clopidogrel-treated patients . Further , the combined use of a CCB and atorvastatin 80 mg daily ( adjusted HR : 0.82 ; 95 % CI : 0.37 to 1.84 ) , or a CCB , statin , and proton pump inhibitor ( adjusted HR : 1.04 ; 95 % CI : 0.70 to 1.54 ) were not associated with an increased risk of CV death , MI , or stroke . The use of statins or CCBs did not modify the relative efficacy of prasugrel versus clopidogrel for the primary endpoint ( p for interaction = 0.43 , 0.55 , respectively ) . CONCLUSIONS In patients with ACS undergoing PCI , the use of statins or CCBs was not associated with an increased risk of CV events in clopidogrel-treated patients . Consistent results were observed when the drugs were administered alone , together , or in combination with proton pump inhibitors OBJECTIVES Scleroderma renal crisis ( SRC ) is a relative rare yet dramatic event in the history of systemic sclerosis ( SSc ) . Several factors that may precipitate or protect from the development of SRC have been described in previous case-control studies . To date , no attempt has been made to evaluate these factors in an observational fashion . METHODS Retrospective data from 410 SSc patients with disease duration < 5 years at referral were evaluated in an observational fashion for the development of hypertensive or normotensive SRC within 5 years from the first visit at our centre . Baseline characteristics as well as the use of steroids or dhiydropyridine calcium-channel blockers ( CCB )  were analysed via the Cox regression method with time-dependent covariates . RESULTS In the multivariate model the diffuse subset the disease ( HR=5.728 CI(95)=2.199 - 14.918 , p<0.001 ) and the use of prednisone  ( HR=1.015 , CI(95)=1.004 - 1.026 , p=0.006 ) result ed to be predictors for the development of SRC , with a risk to develop SRC increased by 1.5 % for every mg of prednisone/day consumed the trimester prior SRC . Contrariwise , the risk to develop SRC was highly reduced in those who were prescribed CCBs ( HR=0.094 , CI(95)=0.038 - 0.236 , p<0.001 ) . CONCLUSIONS Steroids exhibits a weak effect on the risk to progress toward SRC in our case series , whilst dhyidrophyridines CCB appeared to be protective against that . Further larger prospect i ve studies are warranted to better define the role of CCB in this setting or as a background therapy for SSc 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 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 Objective To determine whether a computer-assisted reminder would alter prescribing habits for the treatment of hypertension in accordance with current clinical guidelines in a general internal medicine clinic . Design A r and omized trial . Setting The General Internal Medicine Clinic of the Veterans Affairs Puget Sound Health Care System , Seattle Division . Patients / Participants Clinic providers were r and omized to a control group ( n=35 ) or intervention group ( n=36 ) . We targeted the providers of patients being treated for hypertension with calcium channel blockers , a class of drug not recommended for initial therapy . InterventionAn automated computer query identified eligible patients and their providers . A guideline reminder was placed in the charts of patients of intervention providers ; the charts of patients of control providers received no reminder . Measurements and main results During the 5-month study period , 346 patients were seen by the 36 primary care providers ( staff physicians , nurse practitioners , residents , and fellows ) in the intervention group , and 373 patients were seen by the 35 providers in the control group . Intervention providers changed 39 patients ( 11.3 % ) to other medications during the study period , compared with 1 patient ( < 1.0 % ) of control providers ( p<.0001 ) . For patients whose therapy was unchanged , providers noted angina in 23.1 % , indications other than those for hypertension in 9.5 % , intolerable adverse effects with first-line therapy in 13.9 % , and inadequte control with first-line therapy in 13.9 % . Of those patients without provider-indicated contraindications , 23.6 % were switched from calcium channel blockers to first-line agents during the intervention period . Conclusions The use of a computerized , clinic-based intervention increased compliance with guidelines in the treatment of primary hypertension in general , and decreased the use of calcium channel blockers for the treatment of hypertension in particular Background . Tianma Gouteng Yin ( TGY ) is widely used for essential hypertension ( EH ) as adjunctive treatment . Many r and omized clinical trials ( RCTs ) of TGY for EH have been published . However , it has not been evaluated to justify their clinical use and recommendation based on TCM zheng classification . Objectives . To assess the current clinical evidence of TGY as adjunctive treatment for EH with liver yang hyperactivity syndrome ( LYHS ) and liver-kidney yin deficiency syndrome ( LKYDS ) . Search Strategy . 7 electronic data bases were search ed until November 20 , 2012 . Inclusion Criteria . RCTs testing TGY combined with antihypertensive drugs versus antihypertensive drugs were included . Data Extraction and Analyses . Study selection , data extraction , quality assessment , and data analyses were conducted according to the Cochrane st and ards . Results . 22 RCTs were included . Method ological quality was generally low . Except diuretics treatment group , blood pressure was improved in the other 5 subgroups ; zheng was improved in angiotensin converting enzyme inhibitors ( ACEIs ) , calcium channel blockers ( CCBs ) , and “ CCB + ACEI ” treatment groups . The safety of TGY is still uncertain . Conclusions . No confirmed conclusion about the effectiveness and safety of TGY as adjunctive treatment for EH with LYHS and LKYDS could be made . More rigorous trials are needed to confirm the results Background . Studies have provided conflicting results as to the protective role of calcium channel blockers ( CCB ) in  cyclosporine-treated patients with regard to blood pressure control and preservation of renal graft function .  Lacidipine is a dihydropyridine CCB that possesses antioxidative , anti-atherosclerotic , and anti-adhesion properties and was shown to prevent cyclosporine-induced nephrotoxicity in a rat model . Methods . We conducted a multicenter prospect i ve , r and omized , placebo-controlled study in 131 de novo recipients of a cadaveric renal allograft on cyclosporine therapy .  The aim of this 2-year study was to assess the effects of lacidipine on graft function ( plasma iohexol clearance ) , renal plasma flow , anastomotic arterial blood flow , deterioration of renal function , blood pressure , acute rejection , and hospitalization rate . Results . A total of 118 recipients were available for intention-to-treat analysis on efficacy ( lacidipine : n=59 ; placebo : n=59 ) . Graft function assessed by serum creatinine concentration and glomerular filtration rate measured as plasma iohexol clearance , was persistently better in lacidipine-treated patients from 1 year onwards ( respectively , P<0.01 and P<0.05 ) . Renal plasma flow and anastomotic blood flow were not significantly higher in lacidipine-treated patients . Three patients on lacidipine therapy and four on placebo experienced treatment failure defined as an increase in serum creatinine from baseline of more than 60 % ( log-rank test : P=0.57 ) . Study groups did not differ in acute rejection rate , trough blood cyclosporine concentrations , blood pressure , number of antihypertensive drugs , hospitalization rate , and adverse event rate . Conclusions . The use of calcium channel blockers in cyclosporine-treated renal recipients results in a significantly better allograft function at 2 years and this effect is independent of blood pressure lowering 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 Objective : To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs ( NSAID ) and outcome , in particular ( gastrointestinal ) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives . Methods : Eligible patients ( ⩾60 years , with systolic blood pressure 160–219 mm Hg and diastolic blood pressure < 95 mm Hg ) were r and omised to active treatment or placebo . Active treatment consisted of nitrendipine , with the possible addition of enalapril , hydrochlorothiazide , or both , titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg . Patients never taking NSAIDs ( n = 2882 ) were compared with patients on chronic NSAID intake ( n= 861 ) , defined as reporting NSAID intake on at least 50 % of the patient forms . Results : There was a tendency towards lower mortality ( relative hazard rate ( 95 % confidence interval ( CI ) , 0.77 ( 0.56–1.06 ) ) and higher incidence of bleeding ( 1.13 ( 0.63–2.05 ) with chronic NSAID intake . Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points , chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo ( P-value of the interaction term = 0.07 ) . Conclusion : The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo . However , chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo BACKGROUND The carriage of CYP2C19 * 2 and the use of proton-pump inhibitors ( PPIs ) and calcium-channel blockers ( CCBs ) has been associated with the diminished efficacy of clopidogrel . However , previous studies have only assessed the isolated impact of these risk factors for clopidogrel poor response . OBJECTIVES The aim of the present study was to investigate the impact of the combined presence of three risk factors for clopidogrel poor response , that is , the use of CCBs , PPIs and the carriage of CYP2C19 * 2 , on on-treatment platelet reactivity and the occurrence of atherothrombotic events in 725 patients on dual antiplatelet therapy undergoing elective coronary stenting . METHODS In a prospect i ve , follow-up study , on-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry ( LTA ) and the VerifyNow P2Y12 assay . The clinical study endpoint was the composite of all-cause mortality , myocardial infa rct ion , stent thrombosis and stroke at 1 year after stenting . RESULTS Patients with either one or more than one risk factor exhibited increased platelet reactivity ( mean relative increase one risk factor : 11 % and > 1 risk factor : 22 % , respectively ) . Sixty-four events occurred during follow-up ( 8.8 % of the study population ) . Patients with one risk factor for clopidogrel poor response did not have an increased risk of the composite endpoint . However , patients using both CCBs and PPIs and carriers of CYP2C19 * 2 who used CCBs had a statistically significant increased risk of the composite endpoint [ hazard ratio(HR)(adj ) 2.2 95 % CI , 1.0 - 5.3 , P = 0.044 and HR(adj ) 3.3 95 % CI , 1.1 - 9.8 , P = 0.032 , respectively ] . CONCLUSIONS The presence of more than one of the three investigated risk factors for clopidogrel poor response is associated with an increased risk of adverse cardiovascular events within 1 year after elective coronary stenting BACKGROUND The incidence and factors associated with hyperkalemia in patients with chronic kidney disease ( CKD ) treated with angiotensin converting enzyme inhibitors ( ACEIs ) and other antihypertensive drugs  was investigated using the African American Study of Kidney Disease and Hypertension ( AASK ) data base . METHODS A total of 1094 nondiabetic adults with hypertensive CKD ( glomerular filtration rate [ GFR ] , 20 - 65 mL/min/1.73 m(2 ) ) were followed for 3.0 to 6.4 years in the AASK trial . Participants were r and omly assigned to ACEI , beta-blocker ( BB ) , or dihydropyridine calcium channel blocker ( CCB ) . The outcome variables for this analysis were a serum potassium level higher than 5.5 mEq/L ( to convert to millimoles per liter , multiply by 1.0 ) , or a clinical center initiated hyperkalemia stop point . RESULTS A total of 6497 potassium measurements were obtained , and 80 events in 51 subjects were identified ( 76 events driven by a central laboratory result and 4 driven by a clinical center-initiated hyperkalemia stop point ) . Compared with a GFR higher than 50 mL/min/1.73 m(2 ) , after multivariable adjustment , the hazard ratio ( HR ) for hyperkalemia in patients with a GFR between 31 and 40 mL/min/1.73 m(2 ) and a GFR lower than 30 mL/min/1.73 m(2 ) was 3.61 ( 95 % confidence interval [ CI ] , 1.42 - 9.18 [ P = .007 ] ) and 6.81 ( 95 % CI , 2.67 - 17.35 [ P < .001 ] ) , respectively ; there was no increased risk of hyperkalemia if GFR was 41 to 50 mL/min/1.73 m(2 ) . Use of ACEIs was associated with more episodes of hyperkalemia compared with CCB use ( HR , 7.00 ; 95 % CI , 2.29 - 21.39 [ P < .001 ] ) and BB group ( HR , 2.85 ; 95 % CI , 1.50 - 5.42 [ P = .001 ] ) . Diuretic use was associated with a 59 % decreased risk of hyperkalemia . CONCLUSIONS In nondiabetic patients with hypertensive CKD treated with ACEIs , the risk of hyperkalemia is small , particularly if baseline and follow-up GFR is higher than 40 mL/min/1.73 m(2 ) . Including a diuretic in the regimen may markedly reduce risk of hyperkalemia In the double-blind Systolic Hypertension in Europe ( Syst-Eur ) Trial , active treatment was initiated with nitrendipine ( 10 to 40 mg/d ) with the possible addition of enalapril ( 5 to 20 mg/d ) and /or hydrochlorothiazide ( 12.5 to 25 mg/d ) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to < 150 mm Hg . In the control group , matching placebos were used similarly . In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs , this report explored to what extent nitrendipine , administered alone , prevented cardiovascular complications .  Age at r and omization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg . Of 2398 actively treated patients , 1327 took only nitrendipine ( average dose , 23.4 mg/d ) , and 1042 progressed to other treatments including nitrendipine ( n=757 ; 35.7 mg/d ) , enalapril ( n=783 ; 13.4 mg/d ) , and /or hydrochlorothiazide ( n=294 ; 21.0 mg/d ) . Compared with the whole placebo group ( n=2297 ) , patients receiving monotherapy with nitrendipine had 25 % ( P=0.05 ) fewer cardiovascular end points , and those progressing to other active treatments showed decreases ( P</=0 . 01 ) in total mortality ( 40 % ) , stroke ( 59 % ) , and all cardiovascular end points ( 39 % ) . Among the control patients , 863 used only the first-line placebo . Compared with this subgroup , patients receiving monotherapy with nitrendipine showed a nearly 50 % ( P</=0.004 ) reduction of all types of end points , including total and cardiovascular mortality . The full relative benefit from nitrendipine was seen as early as 6 months after r and omization . To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias , the 1327 patients remaining on monotherapy with nitrendipine  were matched by gender , age , previous cardiovascular complications , and systolic blood pressure at entry with an equal number of placebo patients . In this analysis , nitrendipine reduced ( P</=0.05 ) cardiovascular mortality by 41 % , all cardiovascular end points by 33 % , and fatal and nonfatal cardiac end points by 33 % . Despite the limitations inherent in post hoc analyses , the present findings suggest that the calcium channel blocker nitrendipine , given as a single antihypertensive medication , prevents cardiovascular complications in older patients with isolated systolic hypertension Background L-type dihydropyridine calcium channel blockers ( CCBs ) have been implicated in increased cardiovascular events in patients with hypertension , perhaps due to adverse effects on autonomic nervous system ( ANS ) function . Blockade of T-type calcium channels may limit ANS dysfunction by inhibition of T channel-mediated neuroendocrine effects . Objective and design This double-blind , parallel group study compared the effect of nifedipine gastrointestinal transport system ( GITS ) ( L-type CCB ) versus mibefradil ( T-type CCB ) on ANS function in patients with mild – moderate essential hypertension . Methods Sixteen patients ( 10 male , 6 female ; age 57.2 ± 2.3 years ) , diastolic blood pressure ( DBP ) < 95 mmHg were r and omized to  nifedipine 30 mg daily or mibefradil 50 mg daily ( 2 weeks ) , then nifedipine 60 mg daily or mibefradil 100 mg daily ( 4 weeks ) . Sympathetic nervous system activity ( SNSA ) was assessed using norepinephrine kinetics . Parasympathetic nervous system activity ( PSNA ) was assessed from 24 h Holter recordings of heart rate variability ( HRV ) . Non-invasive baroreflex sensitivity ( BRS ) provided integrated assessment of ANS . Results Patient groups were well matched at baseline . Achieved DBP was lower in patients treated with mibefradil compared with nifedipine , ( 83.4 ± 1.7 versus 95.25 ± 3.3 mmHg ) . There were no significant differences in SNSA and BRS between groups , however the root mean square of successive differences and high frequency power ( HFP ) were increased in mibefradil compared with nifedipine-treated patients [ ( + 1.07 ± 1.6 versus −3.36 ± 1.2 ms , P < 0.05 ) and ( + 0.28 ± 0.1 versus −0.23 ± 0.1 ms2 , P < 0.01 ) , respectively ] . Furthermore , Ln HFP/Ln total power was increased from week 0 to week 6 in the mibefradil-treated group , ( 0.71 ± 0.02 versus 0.74 ± 0.03 , P = 0.046 ) . Conclusion No differences existed between effect of L- and T-type CCBs on SNSA and BRS . However , T-type CCBs increased PSNA , independent of achieved changes in heart rate 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 Treatment of hypertension with ACE inhibitors in diabetic patients reduces proteinuria and slows progression of nephropathy compared with agents that do not maintain declines in proteinuria . Calcium channel blockers ( CCBs ) have variable effects on proteinuria ; their long-term effects on progression of diabetic nephropathy are not known . The current study examines the hypothesis that CCBs that maintain reductions in proteinuria slow progression of nephropathy associated with non-insulin dependent diabetes mellitus ( NIDDM ) by a degree comparable to ACE inhibitors , given similar levels of blood pressure control . To test this hypothesis we r and omized 52 patients with NIDDM associated nephropathy and hypertension , mean age of 63 + /- 8 years , to either the ACE inhibitor , lisinopril ( N = 18 ) , nondihydropyridine CCBs ( NDCCBs ) , verapamil SR ( N = 8) or diltiazem SR ( N = 10 ) , or the beta blocker , atenolol ( N = 16 ) . Goal blood pressure was < or = 140/90 mm Hg . Patients were followed for a mean period of 63 + /- 7 months . The primary end point was change in creatinine clearance ( CCr ) slope in each group . There was no significant difference in mean arterial pressure reduction among the groups over the study period ( P = 0.14 ) . The mean rate of decline in CCr was greatest in the atenolol group ( -3.48 ml/min/year/1.73 m2 ; P < 0.0001 ) . There was no difference in the CCr slopes between lisinopril and NDCCBs groups ( P = 0.36 ) . Proteinuria was reduced to a similar extent in the lisinopril and NDCCBs groups ( P > 0.99 ) . Therefore , in persons with renal insufficiency secondary to NIDDM , similar levels of blood pressure control with either lisinopril or NDCCBs slowed progression of renal disease to a greater extent than atenolol . Moreover , this enhanced slowing of renal disease progression correlated with sustained and significant reductions in proteinuria , findings not observed in the atenolol group Objective : To determine the association between discrete antihypertensive drug classes and incident dementia controlling for blood pressure variability ( BPV ) in the preceding 4 years . Methods : A total of 6,537 participants ( mean age 79 years , 62 % women ) in a prospect i ve population -based cohort were followed up for incident dementia . A 4-year time lag period was created to classify drug exposure and measure blood pressure . BPV ( percent coefficient of variation [ CV ] ) was regressed against 9 antihypertensive drug classes ( BPVreg ) . Cox regression models were employed to determine hazard ratios ( HRs ) for incident dementia thereafter according to drug class , adjusted for mean blood pressure , covariates , and BPV or BPVreg . Results : Over a median 8.4 years follow-up ( interquartile range 6.7–9.0 ) , lower dementia risk was associated with nondihydropyridine calcium channel blocker ( HR 0.56 ; 95 % confidence interval [ CI ] 0.31–1.00 , p = 0.05 ) and loop diuretics ( HR 0.45 ; 95 % CI 0.22–0.93 , p = 0.03 ) after adjusting for CV-BPV . Similar findings were obtained in analyses restricted to antihypertensive drug users for nondihydropyridine calcium channel blocker ( HR 0.52 ; 95 % CI 0.28–0.95 , p = 0.03 ) and loop diuretics ( HR 0.40 ; 95 % CI 0.19–0.83 , p = 0.01 ) . All systolic BPV × antihypertensive drug interaction terms were not different from p < 0.05 . Conclusions : Nondihydropyridine calcium channel blocker and loop diuretics were associated with a reduced dementia risk independent of CV-BPV in the preceding 4 years . Systolic BPV was not the primary mechanism through which antihypertensive drug classes lower dementia risk In patients with insufficient blood pressure ( BP ) control , despite using a combination regimen containing an angiotensin receptor blocker and a calcium channel blocker ( CCB ) , whether a greater dose of CCB or adding a diuretic is more effective at lowering BP remains unclear . We conducted a multicenter r and omized clinical trial to compare the efficacy of switching from the daily administration of a single-pill fixed-dose combination of irbesartan ( 100 mg ) and amlodipine ( 5 mg ) to irbesartan ( 100 mg ) with an increased dose of amlodipine ( 10 mg ) ( HD group , n=62 ) or irbesartan ( 100 mg ) and amlodipine ( 5 mg ) with 1 mg of indapamide ( D group , n=63 ) in patients with poorly controlled hypertension .  BP measured at home was monitored by a physician using a telemonitoring system . Between the HD and D groups , no significant differences were observed in morning home BP changes ( mean reduction of systolic/diastolic BP , 1.7/0.9 mmHg ; 95 % confidence intervals , −2.4 to 5.7/−1.4 to 3.2 ; P=0.19/0.37 ) , achievement rate of target BP ( 45.2 % vs. 42.9 % , P=0.80 ) , BP variability independent of the mean ( P⩾0.74 ) , other variability indices ( P⩾0.55 ) and time to stabilization , which was calculated using a fitted analysis ( 13.1 days vs. 11.4 days , P=0.99 ) . Although a significant increase in serum uric acid was observed in the D group ( P<0.0001 ) , neither clinical ly relevant abnormal laboratory test results nor critical BP changes were observed throughout the trial period . Both antihypertensive drug combination strategies were effective treatment options . Further investigation is required to determine the appropriate use of both therapies based on the various pathologies associated with hypertension Summary The ABCD ( Appropriate Blood Pressure Control in Diabetes ) Trial is a large , prospect i ve , r and omized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus ( NIDDM ) design ed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy , retinopathy , cardiovascular disease , and neuropathy in NIDDM . The secondary objective is to determine equivalency of the effects of a calcium channel blocker ( nisoldipine ) and an angiotensin-converting-enzyme inhibitor ( enalapril ) as a first-line antihypertensive agent in the prevention and /or progression of these diabetic vascular complications . The study consists of two study population s aged 40–74 years , 470 hypertensive patients ( diastolic blood pressure of ≥ 90.0 mmHg at time of r and omization ) and 480 normotensive patients ( diastolic blood pressure of 80.0 mmHg at time of r and omization ) . The study duration is 5 years and is scheduled to end in May of 1998 . Patients are r and omized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy . Patients are also r and omized to nisoldipine or enalapril , with open-label medications added if further blood pressure control is necessary . The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance . Secondary outcome measures are urinary albumin excretion , left ventricular hypertrophy , retinopathy , and neuropathy . Cardiovascular morbidity and mortality will also be evaluated . Given the data showing the impact of hypertension on complications in NIDDM , the ABCD Trial is design ed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM . [ Diabetologia ( 1996 ) 39 : 1646–1654 Objective Calcium channel blocker ( CCB ) is one of the most useful antihypertensive agents . However , the activation of the renin – angiotensin system ( RAS ) is an unfavorable characteristic . N-type calcium channel is thought to be involved in catecholamine 's release . Accordingly , N/L-type CCB has a probability of less activation of the RAS . We substantiated the hypothesis that N/L-type CCB , cilnidipine , leads to less activation of the RAS compared with conventional L-type CCB , amlodipine . Design R and omized , cross-over study . Setting Outpatient study . Participants Participants were 110 hypertensive patients [ male/female 46/64 , age 66.3 ± 10.8 years , systolic blood pressure (SBP)/diastolic blood pressure ( DBP ) 161.8 ± 16.9/92.9 ± 12.4 mmHg , s-Cr 0.77 ± 0.32 mg/dl , plasma renin activity  ( PRA ) 0.65 ± 0.63 ng/ml per h , angiotensin I ( AngI ) 70.5 ± 77.3 pg/ml , angiotensin II ( AngII ) 5.2 ± 3.9 pg/ml , plasma aldosterone concentration ( PAC ) 76.3 ± 35.9 pg/ml , urinary albumin excretion ( UAE ) 108.1 ± 284.2 mg/gCr ] . Amlodipine besilate or cilnidipine was administered for 12 weeks in a cross-over manner as a monotherapy with an intention-to-treat fashion by titrating doses . Final doses of amlodipine besilate and cilnidipine were 6.6 ± 2.7 and 13.7 ± 5.1 mg/day , respectively . Main outcome measures Changes in blood pressure , PRA , AngI , AngII , PAC , UAE of baseline and each end of amlodipine besilate and cilnidipine administration . Results Results were as follows ( amlodipine vs. cilnidipine )  : SBP/DBP ( mmHg ) : 135.2 ± 11.7/79.8 ± 9.6 vs. 136.7 ± 13.2/79.5 ± 10.9 , P = 0.22/0.74 ; PRA ( ng/ml per h ) : 1.16 ± 1.03 vs. 0.95 ± 0.78 , P < 0.01 ; AngI ( pg/ml ) : 155.0 ± 306.4 vs. 101.8 ± 92.0 , P < 0.05 ; AngII ( pg/ml ) : 12.0 ± 12.3 vs. 7.1 ± 4.5 , P < 0.001 ; PAC ( pg/ml ) : 81.6 ± 37.9 vs. 74.3 ± 36.2 , P < 0.05 ; UAE ( mg/gCr ) : 145.4 ± 424.5 vs. 58.8 ± 125.1 , P < 0.05 . Thus , in spite of the comparable blood pressure reductions , each level of components of the RAS at cilnidipine administration was significantly lower than those at amlodipine . Apart from this , UAE at cilnidipine administration was also significantly lower than that at amlodipine . Conclusion It is suggested that cilnidipine leads to less activation of the RAS compared with amlodipine for the first time in human clinical patients and therefore cilnidipine might be expected to be superior in organ protection in addition to the antialbuminuric effect Background — Clopidogrel is an inactive prodrug ; it is converted to its active metabolite through the cytochrome P450 ( CYP3A4 ) pathway , which also metabolizes calcium channel blockers ( CCBs ) . Several studies have reported that CCBs reduce the ability of clopidogrel to inhibit platelet aggregability ; one suggested that CCBs reduce the efficacy of clopidogrel . Methods and Results — We performed a post hoc analysis of the Clopidogrel for the Reduction of Events During Observation ( CREDO ) study to compare the treatment effect of clopidogrel in patients on CCBs versus not on CCBs . In CREDO , 2116 patients were r and omly assigned to pretreatment with 300 mg clopidogrel 3–24 hours before a planned percutaneous  coronary  intervention followed by 1 year of 75 mg/d clopidogrel , versus 75 mg clopidogrel at the time of the procedure and continued for 28 days only . The primary end points were a combined end point of death , myocardial infa rct ion , and stroke at 28 days and 1 year . Among the 580 patients ( 27 % ) on CCBs at enrollment , at 28 days , the combined end point was reached in 17 patients ( 6 % ) on clopidogrel versus 28 ( 9 % ) on placebo ( hazard ratio [ HR ] , 0.71 ; 95 % confidence interval [ CI ] , 0.39–1.29 ) . At 1 year , the combined end point was reached in 27 patients ( 10 % ) on clopidogrel versus 46 ( 15 % ) on placebo ( HR , 0.68 ; 95 % CI , 0.42–1.09 ) . The treatment effect of clopidogrel  was similar in patients not on CCBs at 1 year ( HR , 0.78 ; 95 % CI , 0.56–1.09 ) . After adjustment for differences between patients on and not on CCB , there was still no evidence of an interaction between clopidogrel treatment and CCB ( HR for patients not on CCBs , 0.87 ; 95 % CI , 0.62–1.23 ; HR for patients on CCBs , 0.74 ; 95 % CI , 0.45–1.21 ) . Conclusions — In CREDO , there was no evidence that CCBs decrease the efficacy of clopidogrel OBJECTIVE To investigate the association between use of calcium channel blockers ( CCB ) , dihydropyridine ( DHP ) or nondihydropyridine ( nonDHP ) type CCB and risk of developing Alzheimer 's Disease ( AD ) or mortality . There is evidence suggesting that calcium plays a key role in changes in the brain leading to AD . Previous reports suggest a possible role for CCB in the treatment of AD . However , there are some indications that CCB increase mortality in patients with cardiac disease . METHODS Subjects were 1092 participants in the Baltimore Longitudinal Study of Aging ( BLSA ) older than 60 years of age . Data on CCB use was collected prospect ively for up to 19 years . Cox proportional hazards regression was used to estimate relative risks ( RR ) and confidence intervals ( CI ) of AD and mortality associated with use of CCB or use of only DHP or nonDHP-CCB . Analyses were adjusted for gender , education , smoking , blood pressure and history of heart problems . RESULTS Use of DHP-CCB was not associated with a significantly reduced risk of AD compared to non-users , although the estimate of the RR was low with DHP-CCB ( RR = 0.30 , 95 % CI = 0.07 - 1.25 , P = 0.10 ) . Use of nonDHP-CCB was not associated with reduced risk of AD and the estimate of the RR risk was close to one ( RR = 0.82 , 95 % CI = 0.37 - 1.83 , P = 0.63 ) . In addition , there was no increase in mortality among users of DHP-CCB ( RR = 0.64 , 95 % CI = 0.32 - 1.29 , P = 0.21 ) or nonDHP-CCB ( RR = 1.10 , 95 % CI = 0.65 - 1.87 , P = 0.72 ) . CONCLUSION Users of DHP-CCB and nonDHP-CCB in this study did not have a significantly reduced risk of AD Background . Pre‐eclampsia  is one of the most serious and common complications of pregnancy . Nifedipine , a calcium channel blocker , and the vasodilator hydralazine have both been used as antihypertensive agents in this condition . The aim of this study was to determine which of these two agents is the most appropriate antihypertensive in the management of severe pre‐eclampsia BACKGROUND Nocturnal blood pressure ( BP ) is an independent risk factor of cardiovascular events . The NOCTURNE study , a multicenter , r and omized controlled trial ( RCT ) using our recently developed information and communication technology ( ICT ) nocturnal home BP monitoring ( HBPM ) device , was performed to compare the nocturnal HBP-lowering effects of differential ARB-based combination therapies in 411 Japanese patients with nocturnal hypertension ( HT ) . Methods and Results : Patients with nocturnal BP ≥120/70 mmHg at baseline even under ARB therapy ( 100 mg irbesartan daily ) were enrolled . The ARB/CCB combination therapy ( irbesartan 100 mg+amlodipine 5 mg ) achieved a significantly greater reduction in nocturnal home systolic BP ( primary endpoint ) than the ARB/diuretic combination ( daily irbesartan 100 mg+trichlormethiazide 1 mg ) ( -14.4 vs. -10.5 mmHg , P<0.0001 ) , independently of urinary sodium excretion and /or nocturnal BP dipping status . However , the change in nocturnal home systolic BP was comparable among the post-hoc subgroups with higher salt sensitivity ( diabetes , chronic kidney disease , and elderly patients ) . CONCLUSIONS This is the first RCT demonstrating the feasibility of clinical assessment of nocturnal BP by ICT-nocturnal HBPM . The ARB/CCB combination was shown to be superior to ARB/diuretic in patients with uncontrolled nocturnal HT independently of sodium intake , despite the similar impact of the 2 combinations in patients with higher salt sensitivity Angiotensin receptor blockers ( ARBs ) with calcium channel blockers ( CCBs ) or diuretics are a widely used combination therapy for hypertensive patients . The present study aim ed to determine which combination was better for elderly hypertension patients aged ≧ 65 years . We design ed a multicentre , r and omized , open-label , parallel comparison study . Hypertensive out patients aged ≧ 65 years who did not achieve the target blood pressure ( BP < 140/90 mmHg ) with usual dosages of ARBs  were r and omly assigned to switch treatment to losartan 50 mg/hydrochlorothiazide 12.5 mg or amlodipine 5 mg in addition to ARBs . The primary endpoint was a change in the systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) after the 3-month treatment period , while secondary endpoints were changes in the BP , albuminuria , laboratory values , and cognitive function with the mini-mental state examination ( MMSE ) at baseline and after one year . The results from the CAMUI trial should provide new evidence for selecting optimal combination therapies for elderly hypertensive patients CONTEXT Few cardiovascular outcome data are available for blacks with hypertension treated with angiotensin-converting enzyme ( ACE ) inhibitors or calcium channel blockers ( CCBs ) . OBJECTIVE To determine whether an ACE inhibitor or CCB is superior to a thiazide-type diuretic in reducing cardiovascular disease ( CVD ) incidence in racial subgroups . DESIGN , SETTING , AND PARTICIPANTS Prespecified subgroup analysis of ALLHAT , a r and omized , double-blind , active-controlled , clinical outcome trial conducted between February 1994 and March 2002 in 33,357 hypertensive US and Canadian patients aged 55 years or older ( 35 % black ) with at least 1 other cardiovascular risk factor . INTERVENTIONS Antihypertensive regimens initiated with a CCB ( amlodipine ) or an ACE inhibitor ( lisinopril ) vs a thiazide-type diuretic ( chlorthalidone ) . Other medications were added to achieve goal blood pressures ( BPs ) less than 140/90 mm Hg . MAIN OUTCOME MEASURES The primary outcome was combined fatal coronary heart disease ( CHD ) or nonfatal myocardial infa rct ion ( MI ) , analyzed by intention-to-treat . Secondary outcomes included all-cause mortality , stroke , combined CVD ( CHD death , nonfatal MI , stroke , angina , coronary revascularization , heart failure [ HF ] , or peripheral vascular disease ) , and end-stage renal disease . RESULTS No significant difference was found between treatment groups for the primary CHD outcome in either racial subgroup . For amlodipine vs chlorthalidone only , HF was the only prespecified clinical outcome that differed significantly ( overall : relative risk [ RR ] , 1.37 ; 95 % confidence interval [ CI ] , 1.24 - 1.51 ; blacks : RR , 1.46 ; 95 % CI , 1.24 - 1.73 ; nonblacks : RR , 1.32 ; 95 % CI , 1.17 - 1.49 ; P<.001 for each comparison ) with no difference in treatment effects by race ( P = .38 for interaction ) . For lisinopril vs chlorthalidone , results differed by race for systolic BP ( greater decrease in blacks with chlorthalidone ) , stroke , and combined CVD outcomes ( P<.001 , P = .01 , and P = .04 , respectively , for interactions ) . In blacks and nonblacks , respectively , the RRs for stroke were 1.40 ( 95 % CI , 1.17 - 1.68 ) and 1.00 ( 95 % CI , 0.85 - 1.17 ) and for combined CVD were 1.19 ( 95 % CI , 1.09 - 1.30 ) and 1.06 ( 95 % CI , 1.00 - 1.13 ) . For HF , the RRs were 1.30 ( 95 % CI , 1.10 - 1.54 ) and 1.13 ( 95 % CI , 1.00 - 1.28 ) , with no significant interaction by race . Time-dependent BP adjustment did not significantly alter differences in outcome for lisinopril vs chlorthalidone in blacks . CONCLUSIONS In blacks and nonblack subgroups , rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary CHD or any other prespecified clinical outcome , and diuretic-based treatment result ed in the lowest risk of heart failure . While the improved outcomes with chlorthalidone were more pronounced for some outcomes in blacks than in nonblacks , thiazide-type diuretics remain the drugs of choice for initial therapy of hypertension in both black and nonblack hypertensive patients BACKGROUND Nonsteroidal anti-inflammatory drugs ( NSAIDs ) cause substantial morbidity and mortality from upper gastrointestinal tract disease . Ketorolac tromethamine has been singled out as an NSAID with a distinct gastrotoxicity profile . Calcium channel blockers , a class of antihypertensive drugs , have also been found to increase the risk of gastrointestinal tract bleeding . METHODS We identified 1505 patients hospitalized because of upper gastrointestinal tract bleeding and /or perforation , and we r and omly sample d 20,000 controls in the source population . RESULTS The adjusted relative risk ( RR ) for upper gastrointestinal tract bleeding and /or perforation in NSAID users compared with nonusers was 4.4 ( 95 % confidence interval [ CI ] , 3.7 - 5.3 ) . The risk increased with higher daily doses . Ketorolac presented the highest risk ( RR , 24.7 ; 95 % CI , 9.6 - 63.5 ) and piroxicam ranked second ( RR , 9.5 ; 95 % CI , 6.5 - 13.8 ) . Ketorolac was 5 times more gastrotoxic than all other NSAIDs ( RR , 5.5 ; 95 % CI , 2.1 - 14.4 ) . The excess risk with  ketorolac  was observed with both oral and intramuscular administration and was already present during the first week of therapy . Among the various antihypertensive drug classes , beta-blockers were associated with the lowest relative risk ( RR , 1.0 ; 95 % CI , 0.7 - 1.4 ) , and current use of calcium channel blockers with the highest ( RR , 1.7 ; 95 % CI , 1.3 - 2.1 ) . The association with calcium channel blockers declined when adjusting for various markers of comorbidity ( RR , 1.4 ; 95 % CI , 1.1 - 1.8 ) . Past use of calcium channel blockers was also associated with an increased risk ( RR , 1.5 ; 95 % CI , 1.3 - 1.8 ) . CONCLUSIONS The excess risk of major upper gastrointestinal tract complications associated with outpatient use of ketorolac suggests an unfavorable risk-benefit assessment compared with other NSAIDs . More data are required to reduce the uncertainty about the apparent small increased risk of upper gastrointestinal tract bleeding in patients using calcium channel 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 Purpose Use of specific antihypertensive medications ( AHTs ) has been hypothesized to increase breast cancer risk , but results across published studies are inconsistent . Methods We re-evaluated the relationship between AHT use and  breast cancer risk  in a prospect i ve cohort of 3,201 women ≥65 years of age at recruitment now with more than double the length of follow-up ( 12 vs. 5 years ) and substantially more breast cancer diagnoses ( 188 compared with 75 cases ) . We estimated the association between AHT use overall as well as use of specific formulations ( based on data collected annually ) and breast cancer risk using multivariate-adjusted Cox regression . Results Compared with women who reported no use of AHTs , women who had used calcium channel blockers ( CCB ) within the past two years had a 1.6-fold increased risk of breast cancer ( 95 % confidence interval ( CI ) : 1.0–2.5 ) , and in particular , recent users of immediate-release CCBs had a 2.4-fold increased risk ( 95 % CI : 1.3–4.5 ) . Neither ever nor recent use of any other type of AHT was associated with breast cancer risk . Conclusions While the observed association between immediate-release CCBs and breast cancer risk is based on a small sample size and needs to be interpreted cautiously , this result is consistent with others in the literature . However , given declines in use of these preparations in favor of sustained-release CCBs , which was not related to risk , the potential clinical and public health impact of this association is limited . This study also adds to the evidence that other commonly used AHTs are not strongly related to breast cancer risk BACKGROUND Elevated blood glucose levels are reported with thiazide-type diuretic treatment of hypertension . The significance of this finding is uncertain . Our objectives were to compare the effect of first-step antihypertensive drug therapy with thiazide-type diuretic , calcium-channel blocker , or angiotensin-converting enzyme inhibitor on fasting glucose ( FG ) levels and to determine cardiovascular and renal disease risks associated with elevated FG levels and incident diabetes mellitus ( DM ) in 3 treatment groups . METHODS We performed post hoc subgroup analyses from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial ( ALLHAT ) among nondiabetic participants who were r and omized to receive treatment with chlorthalidone ( n = 8419 ) , amlodipine ( n = 4958 ) , or lisinopril ( n = 5034 ) and observed for a mean of 4.9 years . RESULTS Mean FG levels increased during follow-up in all treatment groups . At year 2 , those r and omized to the chlorthalidone group had the greatest increase ( + 8.5 mg/dL [ 0.47 mmol/L ] vs + 5.5 mg/dL [ 0.31 mmol/L ] for amlodipine and + 3.5 mg/dL [ 0.19 mmol/L ] for lisinopril ) . The odds ratios for developing DM with lisinopril ( 0.55 [ 95 % confidence interval , 0.43 - 0.70 ] ) or amlodipine ( 0.73 [ 95 % confidence interval , 0.58 - 0.91 ] ) vs chlorthalidone at 2 years were significantly lower than 1.0 ( P<.01 ) . There was no significant association of FG level change at 2 years with subsequent coronary heart disease , stroke , cardiovascular disease , total mortality , or end-stage renal disease . There was no significant association of incident DM at 2 years with clinical outcomes , except for coronary heart disease ( risk ratio , 1.64 ; P = .006 ) , but the risk ratio was lower and nonsignificant in the chlorthalidone group ( risk ratio , 1.46 ; P = .14 ) . CONCLUSIONS Fasting glucose levels increase in older adults with hypertension regardless of treatment type . For those taking chlorthalidone vs other medications , the risk of developing FG levels higher than 125 mg/dL ( 6.9 mmol/L ) is modestly greater , but there is no conclusive or consistent evidence that this diuretic-associated increase in DM risk increases the risk of clinical events BACKGROUND Calcium channel blockers ( CCBs ) are known to have differential effects on both changes in proteinuria as well as progression of diabetic nephropathy . No clinical study , however , has evaluated whether the differential antiproteinuric effects of CCBs may be explained by their effect on glomerular membrane permeability . We , therefore , tested the hypothesis that certain subclasses of CCBs reduce proteinuria by changing size selectivity of the glomerular membrane , hence changing its permeability . METHODS Twenty-one patients with type 2 diabetes and the presence of nephropathy with hypertension were r and omized to receive either diltiazem CD or nifedipine GITS after baseline data for mean systolic and diastolic pressure , urinary protein excretion , glomerular filtration rate , renal plasma flow , neutral dextran and IgG clearances were obtained . Glomerular filtration rate , renal plasma flow , neutral dextran and IgG clearance were measured every three months , arterial pressure and heart rate every month . Patients were followed for 21 months . RESULTS At 21 months , both patient groups had similar levels of blood pressure control , however , only the diltiazem group had a change in proteinuria ( 4+/-10%delta , nifedipine vs. -57+/-18%delta , diltiazem ; P < 0.001 ) with improvement in glomerular size selectivity and change in IgG clearance . CONCLUSIONS These data support the hypothesis that CCBs that provide sustained reductions in proteinuria do so , in part , by improving glomerular size permselectivity 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 Patients aged 60 years and older with essential hypertension were treated with an angiotensin-converting enzyme inhibitor ( ACE-I ) , delapril ( Adecut ) or a long-acting calcium (Ca)-antagonist , manidipine ( Calslot ) for 3 years . The incidences of cardiovascular events as well as drug-related side effects were compared between the two groups to investigate whether both classes of antihypertensive drugs are beneficial in elderly hypertensive patients . There were no significant differences in characteristics of patients between the two intervention groups , except for slightly lower blood pressure ( P = .08 ) in the Ca-antagonist group at the initiation of the study . There were no significant differences in total death between the two groups . Cardiovascular events ( both fatal and nonfatal ) were noted in 34 of 699 patients ( 22.5/1000 patient-years ) in the ACE-I group and 50 of 1049 patients ( 19.7/1000 patient-years ) in the Ca-antagonist group , with no significant difference found between the two groups . The correlation between cardiovascular incidence and the blood pressure attained during treatment showed a J-shaped phenomenon and suggests that an excessive reduction less than 120 mm Hg in systolic blood pressure ( SBP ) is unnecessary and may be harmful in certain cases . Side effects were more frequent in the ACE-I group than in the Ca-antagonist group ( P = .01 ) . Cough was the major adverse event , occurring in 5.0 % of patients in the ACE-I group . In conclusion , the study indicates that both ACE-I ( delapril ) and Ca-antagonist ( manidipine ) were equally beneficial for reducing cardiovascular morbidity and mortality in elderly hypertensive patients . However , tolerability of ACE-I was lower due to the adverse event of coughing
Diuretics are preferred first-line over CCBs to optimize reduction of cardiovascular events .
The review does not distinguish between CCBs , ACE inhibitors or ARBs , but does provide evidence supporting the use of CCBs over beta-blockers .
BACKGROUND Calcium channel blockers ( CCBs ) are a relatively new antihypertensive class .
The effect of first-line CCBs on the prevention of cardiovascular events , as compared with other antihypertensive drug classes , is unknown .
OBJECTIVES To determine whether CCBs used as first-line therapy for hypertension are different from other first-line drug classes in reducing the incidence of major adverse cardiovascular events .