Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. Comparative study of high dose mono-therapy of amlodipine or telmisartan, and their low dose combination in mild to moderate hypertension. ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil. The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. Relaxation therapy for hypertension. Comparison of effects with concomitant placebo, diuretic, and beta-blocker. Oral labetalol versus oral nifedipine in hypertensive urgencies in the ED. Plasma renin activity predicts blood pressure responses to beta-blocker and thiazide diuretic as monotherapy and add-on therapy for hypertension. Efficacy of various antihypertensive agents as evaluated by indices of vascular stiffness in elderly hypertensive patients. To compare the effect of Telmisartan with Metoprolol on arterial stiffness in hypertension: prospective randomized parallel group trial. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects. The stroke preventive effect in elderly hypertensives cannot fully be explained by the reduction in office blood pressure--insights from the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension). Controlled-release carvedilol in the treatment of essential hypertension. Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives 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 Low-dose bisoprolol/hydrochlorothiazide: an option in first-line, antihypertensive treatment. Influence of pretreatment systolic blood pressure on the effect of carvedilol in patients with severe chronic heart failure: the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study. A 16-week, randomized, double-blind, placebo-controlled, crossover trial to quantify the combined effect of an angiotensin-converting enzyme inhibitor and a beta-blocker on blood pressure reduction. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group. Efficacy of Combination Antihypertensive Therapy with Low-Dose Indapamide: Assessment by Blood Pressure Self-Monitoring at Home Management of hypertension and the core services guidelines: results from interviews with 100 Auckland general practitioners. A comparison of the efficacy and safety of a beta-blocker, a calcium channel blocker, and a converting enzyme inhibitor in hypertensive blacks. South African hypertension guideline 2011. The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Antihypertensive efficacy of zofenopril compared with atenolol in patients with mild to moderate hypertension [Atenolol and bisoprolol in the treatment of mild and moderately severe hypertension]. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. A randomized prospective crossover trial of amlodipine in pediatric hypertension Status of Hypertension in China: Results From the China Hypertension Survey, 2012–2015 The efficacy and tolerability of nebivolol in hypertensive African American patients. Nutritional dose of magnesium in hypertensive patients on beta blockers lowers systolic blood pressure: a double-blind, cross-over study.
Objective : To compare the blood pressure‐lowering efficacy , the frequency of side effects and changes in laboratory values of three & bgr;‐blockers and a potassium‐sparing diuretic combination in elderly hypertensive patients . Design : The Swedish Trial in Old Patients with Hypertension ( STOP‐Hypertension ) was a prospect i ve , r and omized , double‐blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70‐84 years . Methods : The study group consisted of 1627 elderly hypertensive patients ( mean ± SD age 75.7 ± 3.7 years ; 37 % males , 63 % females ) . Supine and st and ing blood pressure , heart rate and side effects were recorded at each visit . Blood was drawn for routine analysis . The mean length of follow‐up was 25 months ( range 6‐65 ) . No patient was lost to follow‐up . Results : After 2‐months ' single‐drug therapy , all four active drugs were found to be equally effective in reducing diastolic blood pressure ( DBP ) . However , there were differences in their efficacy in reducing systolic blood pressure ( SBP ) ; the diuretic was significantly more effective than the & bgr;‐receptor blockers . The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate . More than two‐thirds of the patients were given supplementary treatment , most of them already by the 2‐month visit , after which there was no significant difference in blood pressure among the treatment regimens . The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens . Conclusion : Metoprolol ( controlled release ) , atenolol , pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP . There were differences in their efficacy in reducing SBP , the diuretic being more effective than the & bgr;‐blockers . After addition of supplementary treatment ( & bgr;‐blocker to diuretic , or vice versa ) there were no significant differences in blood pressure reduction among the groups . The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens . Thus , the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs A large-scale , 8-week , open-label , clinical experience trial evaluated the efficacy of the angiotensin II receptor ( AT1 subtype ) blocker c and esartan cilexetil ( 16 to 32 mg once daily ) either alone or as add-on therapy in 6465 hypertensive patients . The study population was 52 % female and 16 % African American with a mean age of 58 years . It included 5,446 patients who had essential hypertension ( HBP ) and 1,014 patients who had isolated systolic hypertension ( ISH ) . These patients had either untreated or uncontrolled hypertension ( systolic blood pressure [ SBP ] 140 to 179 mm Hg or diastolic blood pressure [ DBP ] 90 to 109 mm Hg inclusive at baseline ) despite a variety of antihypertensive medications including diuretics , calcium antagonists , angiotensin converting enzyme ( ACE ) inhibitors , and alpha- or beta-blockers , either singly or in combination . The mean baseline blood pressure for the HBP group was 156/97 mm Hg . C and esartan cilexetil as monotherapy ( in 51 % of HBP patients ) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg . As add-on therapy ( in 49 % of HBP patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.8/11.3 mm Hg ) , calcium antagonists ( 16.6/11.2 mm Hg ) , beta-blockers ( 16.5/ 10.4 mm Hg ) , ACE inhibitors ( 15.3/10.0 mm Hg ) , alpha-blockers ( 16.4/10.4 mm Hg ) . The mean baseline blood pressure for the ISH group was 158/81 mm Hg . C and esartan cilexetil , as monotherapy ( in 34 % of ISH patients ) , reduced SBP/DBP by 17.0/4.4 mm Hg . As add-on therapy ( in 66 % of ISH patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.4/5.1 mm Hg ) , calcium antagonists ( 15.6/3.6 mm Hg ) , beta-blockers ( 14.0/4.8 mm Hg ) , ACE inhibitors ( 13.4/4.3 mm Hg ) , and alpha-blockers ( 11.6/4.5 mm Hg ) . The further blood pressure lowering effects of c and esartan cilexetil as add-on therapy were seen regardless of age , sex , and race . Overall , 6.8 % of the 6465 patients withdrew because of adverse events , most commonly headache ( 6.3 % ) and dizziness ( 5.0 % ) . Orthostatic hypotension was infrequent ; 0.2 % with c and esartan cilexetil alone , and 0.8 % with c and esartan cilexetil as add-on therapy . Thus , c and esartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice setting 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 The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal Men aged 40 - 64 years with mild to moderate hypertension [ diastolic blood pressure ( DBP ) 100 - 130 mmHg ] were r and omized to treatment with a  diuretic ( n = 3272 ) or a  beta-blocker ( n = 3297 ) , with additional drugs if necessary , to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease ( CHD ) events and death .  Patients with previous CHD , stroke or other serious diseases , or with contraindications to diuretics or beta-blockers were excluded . If normotension ( DBP less than 95 mmHg ) was not achieved by monotherapy , other antihypertensive drugs were added , but the two basic drugs were not crossed over . Patients were assessed at 6-monthly intervals . The mean follow-up for end-points was 45.1 months . Blood pressure ( BP ) side effects and end-points were recorded in a st and ardized manner . Entry characteristics and the BP reduction achieved were very similar in both treatment groups . All analyses were made on an intention-to-treat basis . The incidence of CHD did not differ between the two treatment groups . The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group . Total mortality and the total number of end-points were similar in both groups . The percentage of patients withdrawn due to side effects was similar , whereas the number of reported symptoms , according to a question naire , was higher for patients on beta-blockers . The incidence of diabetes did not differ between the two groups . Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers , and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD . Beta-blockers and thiazide diuretics were approximately equally well tolerated . The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group . Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications , including CHD , to a different extent BACKGROUND Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effects of diuretics , beta-blockers , angiotensin-converting enzyme inhibitors , central alpha-agonists , and other vasodilators . Their effects on the antihypertensive efficacy of calcium channel blockers are inadequately studied in small numbers of patients but appear to be minimal . METHODS A three-phase , r and omized , double-blind , placebo-controlled  multicenter study included 162 patients aged 18 to 75 years with essential hypertension . After diastolic blood pressure was controlled to 90 mm Hg or less with once-daily verapamil hydrochloride , patients received ibuprofen , naproxen , or placebo matching capsules for 3 weeks , and blood pressure , heart rate , weight , and adverse effects were evaluated . A general linear model with 95 % confidence intervals was used to compare each nonsteroidal anti-inflammatory drug treatment group with the placebo group . RESULTS No significant differences in sitting , st and ing , or supine blood pressure were noted with naproxen or ibuprofen compared with placebo . The percentages of patients in each treatment group with increases of 10 mm Hg or more in either systolic or diastolic blood pressure were similar . Statistically significant increases in weight were seen with both nonsteroidal anti-inflammatory drug therapies . Changes in pulse rate were not significant . The incidence of adverse effects was similar across all three treatment groups . CONCLUSIONS The addition of naproxen or ibuprofen to the treatment of hypertensive patients in whom blood pressure is controlled by once-daily verapamil does not cause an increase in blood pressure .  Verapamil may therefore offer considerable advantages in maintaining control of blood pressure in patients who regularly receive nonsteroidal anti-inflammatory drug therapy OBJECTIVE 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 The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated . A total of 127 adult out patients with diastolic blood pressure between 100 and 114 mmHg were r and omized into this double-blind , parallel group study . After a 2-week wash-out period and a subsequent 2-week placebo run-in period , they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide ( R/C ) , or 5 mg enalapril . If diastolic blood pressure was not normalized after 3 weeks of therapy ( i.e. DBP < 90 mmHg ) , the dosage was doubled from week 4 to 6 . The primary efficacy variables were the change from baseline in mean sitting diastolic and systolic blood pressure ( DBP/SBP ) after 3 weeks of therapy . Secondary variables included the change in DBP and SBP after 6 weeks of therapy , the BP normalization rates at 3 and 6 weeks and , concerning tolerability , the rates of adverse events after 6 weeks of therapy . An intent-to-treat analysis was performed . The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics ( mean age 57 or 58 years , respectively ; 63 % or 56 % males , respectively ; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups ) . After 3 weeks of treatment with one capsule daily , mean SBP/DBP reduction from baseline ( 24 h after last medication intake ) in the R/C combination group was -19.6/ -17.0 mmHg , in the enalapril group -6.1/ -9.5 mmHg ( between-group comparison : 2p < 0.01 for both parameters ) . The normalization rates for DBP ( < 90 mmHg ) were 64.1 % ( R/C ) and 28.6 % ( enalapril ) ( 2p < 0.01 ) . Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients ( 17.2 % ) in the R/C group and in 9 patients ( 14.3 % ) in the enalapril group ( NS ) . Two patients in the enalapril group discontinued the study prematurely due to adverse events ( cough ; skin eruption ) . In the treatment of mild-to-moderate hypertension , a low-dose combination of reserpine and clopamide once a day is considerably more effective than , and as tolerable as , 5 - 10 mg of enalapril once a day . These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension . Besides , the " old " reserpine-diuretic regimen also in these days appears to be a rational alternative to " modern " monotherapies We compared the effects of relaxation therapy in hypertensive patients taking placebo , a beta-blocker ( atenolol , 100 mg/d ) , or a diuretic ( chlorthalidone , 50 mg/d ) , and we also compared the effects of relaxation therapy with the effects of the latter two drugs alone . Blood pressures were measured not only in the relaxation therapists ' office and at a hypertension clinic , but also in the patient 's environment by means of 24-hour ambulatory blood pressure recordings . The effect of relaxation therapy , while statistically significant , was modest . There was no generalization of effect to ambulatory blood pressure .  Atenolol was significantly more effective than  relaxation  in reducing both systolic and diastolic pressure .  Chlorthalidone was significantly more effective than relaxation in reducing systolic but not diastolic pressure in the hypertension clinic only . The long-term effects of relaxation were independent of concomitant drug use , but within the actual relaxation sessions blood pressure dropped further during chlorthalidone than during placebo or atenolol treatment Therapy in hypertensive urgencies is debated and complicated by the side effects of available agents . In a prospect i ve , r and omized , open labeled study , the use of oral labetalol , an alpha- and beta-adrenergic blocker , with oral nifedipine in hypertensive urgencies in the emergency department was compared . Patients with diastolic blood pressures ( DBP ) of more than 120 mm Hg without criteria for a hypertensive emergency were eligible . The drugs were given in a loading manner with doses and timing based on their respective pharmacokinetics until a DBP of 110 mm Hg or lower was obtained or 4 hours had passed . Either an initial labetalol dose of 200 mg and a repeat dose of 100 to 200 mg at 2 hours , depending on the DBP or nifedipine , 10-mg bite and swallow every hour up to a total dose of 20 mg were given . Ten patients were enrolled into each study group . A 100 % response rate was defined as a DBP of 110 mm Hg or less was observed for nifedipine and an 80 % response rate for labetalol ( P > .2 ) was observed . The mean time to control was 67.5 minutes for labetalol and 60.0 minutes for nifedipine ( P > .2 ) . The pretreatment pressure for labetalol was 195/127 mm Hg and for nifedipine was 198/128 mm Hg ( P > .2 ) , which decreased to a posttreatment pressure for labetalol of 154/100 mm Hg and for nifedipine of 163/100 mm Hg ( P > .2 ) . The mean decrease in systolic (SBP)/DBP was 42.6/26.5 mm Hg with labetalol and 34.9/28.4 mm Hg for nifedipine ( P > .2 ) . No significant side effects occurred with either drug . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND Age and race categories or renin profiling have been recommended to predict blood pressure responses to monotherapy with a beta-blocker or thiazide diuretic . Whether these or other characteristics predict blood pressure responses when the drugs are administered as add-on therapy is uncertain . METHODS We evaluated predictors of blood pressure response in 363 men and women < or = 65 years of age with primary hypertension ( 152 blacks , 211 whites ) , 86 of whom ( 24 % ) were untreated and 277 of whom ( 76 % ) were withdrawn from previous antihypertensive drugs before r and omization to either atenolol followed by addition of hydrochlorothiazide ( N = 180 ) or hydrochlorothiazide followed by addition of atenolol ( N = 183 ) . Responses were determined by home blood pressure averages before and after each drug administration . Race , age , plasma renin activity , and other characteristics including pretreatment blood pressure levels were incorporated into linear regression models to quantify their contributions to prediction of blood pressure responses . RESULTS Plasma renin activity and pretreatment blood pressure level consistently contributed to prediction of systolic and diastolic responses to each drug administered as mono- and as add-on therapy . Higher plasma renin activity was consistently associated with greater blood pressure responses to atenolol and lesser responses to hydrochlorothiazide . The predictive effects of plasma renin activity were statistically independent of race , age , and other characteristics . CONCLUSIONS Plasma renin activity and pretreatment blood pressure level predict blood pressure responses to atenolol and hydrochlorothiazide administered as mono- and as add-on therapy in men and women < or = 65 years of age When observed in elderly hypertensive patients , increased pulse pressure ( PP ) and arterial stiffness are known to be independent risk factors for cardiovascular diseases . Increased systolic blood pressure ( SBP ) leads to left ventricular hypertrophy , while decreased diastolic blood pressure ( DBP ) results in decreased coronary circulation . It is known that increased arterial stiffness is the major cause of increased PP . Thus basic morbid states of cardiac failure or ischemic heart diseases are more likely to develop in elderly hypertensive patients with increased PP and arterial stiffness , and there is need of antihypertensive drugs that decrease these effects in elderly hypertensives . In this study , we compared the effects of an angiotensin-receptor blocker ( ARB : valsartan ) , an angiotensin-converting enzyme inhibitor ( ACE-I : temocapril ) , and long-acting Ca antagonists ( L- and N-type Ca channel blocker : cilnidipine ; and L-type Ca channel blocker : nifedipine CR ) on PP and arterial stiffness measured by pulse wave velocity in elderly hypertensive patients for 3 months . The ARB yielded the largest reductions in PP and brachial-ankle pulse wave velocity ( baPWV ) , followed by the ACE-I and L- and N-type Ca channel blocker , while the L-type Ca channel blocker yielded no improvement . The effects on arterial stiffness and PP thus varied among the drug characteristics . Although ARB achieved the largest reduction in baPWV , this decrease was not associated with any reductions in PP , SBP , DBP , or mean blood pressure , as were the baPWV-decreases achieved by the other drugs , suggesting that ARB may further reduce the risk of arteriosclerosis in elderly hypertensive patients by decreasing arterial stiffness in addition to its antihypertensive effect BACKGROUND Hypertension is often complicated by increased arterial stiffness and is an independent predictor of adverse cardiovascular ( CV ) outcome . Beta blockers and angiotensin receptor blockers ( ARBs ) are commonly used antihypertensive agents . The effect of beta blockers and ARBs on arterial stiffness has not been compared adequately . The aim of the present study is to compare the effect of telmisartan with metoprolol on arterial stiffness in hypertensive patients in prospect i ve open label r and omized parallel group intervention study . METHODS 100 patients of hypertension , not on any antihypertensive agents , were enrolled after obtaining informed consent . Baseline recording of data related to demographics , CV risk factors , anthropometry and BP were made . Arterial stiffness was measured noninvasively by recording pulse wave velocity ( PWV ) using periscope ( Genesis medical system ) . Left ventricular ( LV ) mass was measured using 2D guided M-mode echocardiography . Blood sugar , renal function , lipids and uric acid estimations were done in fasting state . Patients were r and omized to receive metoprolol and telmisartan using stratified r and omization technique . Dose of the study drugs were titrated to achieve target BP of < 140/90 mmHg . Data related to PWV , BP , anthropometry and blood biochemistry was repeated after 6 months of treatment with study drugs . RESULTS Telmisartan result ed in significantly greater reduction in arterial stiffness index ( ASI ) in left and right lower limb arterial bed ( 39.9 ± 11.7 vs. 46.8 ± 17.0 m/s , p < 0.02 ) and ( 36.4 ± 9.6 vs. 44.86 ± 15.1 m/s , p < 0.002 ) respectively and systolic blood pressure ( SBP ) ( -4.9 mmHg with 95 % C.I. of -8.0 - 1.7 mmHg , p < 0.003 ) compared to metoprolol . Reduction in diastolic blood pressure ( DBP ) in telmisartan and metoprolol groups was not different statistically ( -1.0 mmHg with 95 % C.I. of -3.3 - 1.2 mmHg , p < 0.3 ) . The change in LV mass was not significantly different between the study groups ( 135.5 ± 37.6 vs. 143.2 ± 41.5 , p < 0.3 ) BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality  in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p<0.001 ) . A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group ( 16.6 vs 16.2 events per 1000 patient-years ; relative risk 1.00 [ 95 % CI 0.87 - 1.15 ] , p=0.97 ) . Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients . Thirteen obese , hypertensive patients with a body mass index ( BMI ) > or = 28 kg/m2 ( obese ) and nine lean patients with a BMI < or = 25 kg/m2 ( lean ) were recruited . After a 1-week washout period , participants underwent daytime ambulatory blood pressure monitoring  ( ABPM ) . Participants were then treated with the alpha-adrenergic antagonist doxazosin , titrating to 4 mg QHS in 1 week . In the next week , the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week . One month after the addition of atenolol , all patients underwent a second ABPM session . There were no differences between the obese and lean subjects in baseline systolic ( SBP ) , diastolic ( DBP ) , or mean arterial pressures ( MAP ) measured by office recording or ABPM . However , obese subjects had higher heart rates than lean subjects ( 87.5+/-2.4 v 76.8+/-4.9 beats/min ) . After 1 month of treatment with the adrenergic blockers , obese patients had a significantly lower SBP ( 130.0+/-2.5 v 138.9+/-2.1 mm Hg , P = .02 ) and MAP ( 99.6+/-2.3 v 107.0+/-1.5 mm Hg , P = .02 ) than lean patients . Obese patients also tended to have a lower DBP than lean patients ( 84.3+/-2.5 v 90.9+/-1.6 mm Hg , P = .057 ) , but there was no significant difference in heart rate after 1 month of adrenergic blockade . These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity OBJECTIVE To study whether the cardiovascular preventive effect of antihypertensive therapy can be explained solely by the reduction in office blood pressure , and to what extent the risk of stroke and cardiac events is associated with in- study diastolic blood pressure ( DBP ) and systolic blood pressure ( SBP ) . DESIGN The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omized , double-blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70 - 84 years . The study group comprised 1,627 elderly patients ( mean blood pressure 195/102 mm Hg ; mean age 75.7 , SD 3.7 ; 63 % females ) . The average follow-up was 25 months ( range 6 - 65 months ) . No patient was lost to follow-up . METHOD We applied a Poisson model taking current age , sex , treatment , DBP and SBP into account for all patients in the study . The constants of the model were estimated by the maximum likelihood method . RESULTS The risk of stroke was significantly lower ( 42 % , p = 0.0402 ) for a patient on active therapy than for a patient on placebo having the same blood pressure level , age , and sex . There was a corresponding , non-significant , reduction in cardiac events of 21 % . In the whole study group the risk of stroke increased by 3 % per mmHg ( p = 0.0247 ) with increasing diastolic blood pressure for a given systolic pressure . The corresponding value for cardiac events was 2 % per mmHg ( p = 0.0376 ) . CONCLUSION In STOP-Hypertension we found a substantial risk reduction in stroke in actively treated patients , which was not solely explained by the blood pressure reduction obtained by treatment with beta-blockers and a potassium-sparing diuretic combination Carvedilol is a beta1- , beta2- , and alpha1-adrenergic blocker that is approved for the treatment of hypertension . A new once-daily , controlled-release ( CR ) formulation of carvedilol has been shown to be effective in a double-blind , r and omized , multicenter , placebo-controlled , parallel-group study . In this article , we summarize the primary results of , and present additional analyses from , that trial . A total of 338 patients with essential hypertension ( sitting diastolic blood pressure [ DBP ] > /=90 and < /=109 mm Hg ) were r and omized to receive carvedilol CR 20 , 40 , or 80 mg or placebo for 6 weeks . The primary objective was to compare the effects of the 3 carvedilol CR doses with placebo on 24-hour mean blood pressure using ambulatory blood pressure monitoring ( ABPM ) . Mean DBP and systolic BP ( SBP ) at the drug trough ( 20 - 24 hour ) blood levels for carvedilol CR and comparison of DBP and SBP at the drug peak ( 3 - 7 hour ) blood levels for each dose of carvedilol CR and placebo were investigated . The effects of carvedilol CR on heart rate and pulse pressure were also examined . Once-daily administration of carvedilol CR , alone or in combination with other agents , produced clinical ly and statistically significant reductions compared with placebo for both DBP and SBP after 6 weeks of treatment for the following parameters : trough blood pressure by office cuff or ABPM measurements , peak blood pressure by ABPM , and 24-hour mean blood pressure by ABPM . Placebo-corrected trough-to-peak ratios for DBP were > 0.6 for each carvedilol CR dose . Heart rate and pulse pressure were each significantly reduced compared with placebo for each carvedilol CR dose . We conclude that carvedilol CR is a very effective antihypertensive agent with clear dose-related peak blood pressure reduction and continuous 24-hour control Aerobic physical exercise is broadly recommended as a helpful adjunct to obtain blood pressure control in hypertension . Beta-blockade interacts with heart rate , sympathetic tone , maximal workload and local lactate production . In the present r and omized-controlled study , we compared the cardiovascular effects of an endurance training programme in elderly hypertensives with or without beta-blockers and developed a first approach to determine a lactate-based training heart rate in presence of beta-blockade . Fifty-two patients ( 23 with beta-blocker , 29 without beta-blocker ) ⩾60 years with systolic 24-h ambulatory blood pressure ( ABP ) ⩾140 mm Hg and /or antihypertensive treatment were r and omly assigned to sedentary activity or a heart-rate controlled 12-week treadmill exercise programme ( lactate 2.0 mmol/l ) . In the exercise group , the training significantly decreased systolic and diastolic 24-h ABP , blood pressure on exertion ( 100 W ) and increased endothelium-dependent vasodilation ( flow-mediated vasodilation , FMD ) and physical performance both in the presence and absence of beta-blockade ( P<0.05 each ) . The extent of ABP reduction did not significantly differ in the presence or absence of beta-blockade ( Δ systolic ABP 10.6±10.5 vs 10.6±8.8 mm Hg , Δ diastolic ABP 5.7±8.6 vs 5.8±4.0 mm Hg ) . Mean training heart rate was significantly lower in the patients on beta-blockers ( 97.2±7.7 vs 118.3±7.5/min , P<0.001 ) . Lactate-based aerobic endurance training evokes comparable cardiovascular benefits in the presence and absence of beta-blockade including a marked improvement of endothelial function . In the present study , target training heart rate with beta-blockers is about 18 % lower than without 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 Two recent , multicenter , double-blind , placebo-controlled studies established the efficacy and safety of low-dose bisoprolol/hydrochlorothiazide ( HCTZ ) in patients with mild to moderate essential hypertension .  Bisoprolol , a cardioselective beta-blocker , was used in a dose of 2.5 mg , 5 mg , or 10 mg . HCTZ was used at a dose of 6.25 mg . This low-dose compound was developed to minimize dose-related adverse effects . The addition of HCTZ to each of the doses of bisoprolol was compared with monotherapy and placebo . Results of both studies demonstrated that this once-a-day , low-dose option effectively reduced sitting diastolic and systolic blood pressure measured at the end of the 24-hour dosing period . Drug-related adverse effects , including those generally associated with traditional beta-blocker therapy , were infrequent in individuals who received the low-dose bisoprolol/HCTZ regimen . Dose-related side effects were minimized because of the low doses of the two agents used together . There were no significant changes in mean total cholesterol , triglycerides , or serum glucose with bisoprolol/HCTZ 6.25 mg therapy versus placebo ( analysis of variance statistical methods ) . The incidence of treatment-induced hypokalemia with bisoprolol/HCTZ 6.25 mg was not significant ; uric acid elevations were minimized , and the incidence of hyperuricemia was significantly ( P < 0.01 ) less with bisoprolol/HCTZ 6.25 mg than with 25 mg of HCTZ . Once-a-day dosing with the low-dose agent controlled ( defined as a sitting diastolic blood pressure < or = 90 mmHg and /or a decrease from baseline > or = 10 mmHg ) blood pressure in up to 80 % of patients for a full 24 hours after dosing . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES We sought to evaluate the influence of pretreatment systolic blood pressure ( SBP ) on the efficacy and safety of carvedilol in patients with chronic heart failure ( CHF ) . BACKGROUND Although beta-blockers reduce the risk of death in CHF , there is little reported experience with these drugs in patients with a low pretreatment SBP , who may respond poorly to beta-blockade . METHODS We studied 2,289 patients with severe CHF who participated in the Carvedilol Prospect i ve R and omized Cumulative Survival ( COPERNICUS ) trial . RESULTS Compared with placebo , carvedilol improved the clinical status and reduced the risk of death and the combined risk of death or hospitalization for any reason , for a cardiovascular reason , or for worsening heart failure ( p < 0.001 for all ) . The relative magnitude of these benefits did not vary as a function of the pretreatment SBP ( all interaction : p > 0.10 ) . However , because patients with the lowest SBP were at highest risk of an event , they experienced the greatest absolute benefit from treatment with carvedilol . The lower the pretreatment SBP , the more likely that patients would report an adverse event , be intolerant of high doses of the study drug , or require permanent withdrawal of treatment ( p < 0.001 for all ) . However , these risks were primarily related to the severity of the underlying illness and not to treatment with carvedilol . CONCLUSIONS The current study provides little support for concerns about using beta-blockers ( particularly those with vasodilatory actions ) in patients with severe CHF who have a low SBP . Pretreatment blood pressure can identify patients who have the greatest need for risk reduction with carvedilol BACKGROUND Although beta-blockers and angiotensin-converting enzyme ( ACE ) inhibitors are often used together , there is a lack of quantitative evidence for the efficacy of this combination in reducing  blood pressure ( BP ) .  OBJECTIVE The aim of this r and omized , double-blind , placebo-controlled , crossover study was to quantify the combined effect of a beta-blocker ( atenolol ) and an ACE inhibitor ( lisinopril ) in lowering BP . METHODS Participants who were > or = 40 years of age and enrolled in the hypertension or anticoagulation clinics at St. Bartholomew 's Hospital , London , United Kingdom , were r and omized to 3 consecutive 4-week treatments consisting of atenolol 25 mg plus placebo , lisinopril 5 mg plus placebo , and atenolol 25 mg plus lisinopril 5 mg , plus a period of 2 placebos . At the end of each period , seated BP was measured in the right arm using electronic monitors . RESULTS The mean  placebo-adjusted peak BP reductions among the 47 participants ( mean age , 62 [ range 42 - 82 ] years ; 75 % male ; 70 % white/30 % Asian ; mean baseline BP , 145/82 mm Hg ) who completed all 4 periods were significantly greater with the combination of both drugs than with either drug alone ( P < 0.001 ) . The systolic reductions were 22.9 mm Hg with combination treatment , 16.1 mm Hg with atenolol treatment , and 12.5 mm Hg with lisinopril treatment , and the diastolic reductions were 13.9 , 9.8 , and 6.8 mm Hg , respectively . The BP-lowering effect of the 2 drugs together was similar to that expected from the sum of each alone , allowing for the reduced effect of 1 drug given the lower pretreatment BP due to the other . The incremental systolic BP reduction from the 2 drugs together compared with 1 alone was 79 % ( 95 % CI , 54%-126 % ) of the expected additive effect , 88 % ( 95 % CI , 58%-130 % ) for diastolic BP , and 84 % ( 95 % CI , 65%-118 % ) for the mean of systolic and diastolic BP . CONCLUSIONS The combination of the beta-blocker atenolol 25 mg plus the ACE inhibitor lisinopril 5 mg was associated with a significantly greater decrease in BP compared with either alone . The BP reduction with the combination treatment was similar to and statistically consistent with the 2 drugs having additive effects . Clinical Trials Identification Number : IS RCT N97280940 Myocardial infa rct ion , sudden cardiac death , cerebrovascular accidents , blood pressure control and treatment tolerability were studied in a r and omized double-blind trial conducted in 6357 men and women aged 40 - 64 years with uncomplicated essential hypertension ( diastolic blood pressures 100 - 125 mmHg ) . At the start of the trial 3185 patients received treatment based on a beta-blocker ( oxprenolol )  , while in the remaining 3172 placebo replaced oxprenolol .  Supplementary drugs , excluding beta-blockers , were used as necessary in both treatment groups , with the aim of reducing diastolic pressure to 95 mmHg or less . Patients were followed for 3 - 5 years , a total of 25 651 patient years at risk . In most respects the two groups fared equally well ; sudden death ( relative risk [ RR ] 1.08 ; 95 % confidence interval [ Cl ] 0.68 and 1.72 ) , myocardial infa rct ion ( RR 0.83 ; Cl 0.59 and 1.16 ) and cerebrovascular accident ( RR 0.97 ; Cl 0.64 and 1.47 ) rates were similar . Beta-blocker based therapy was associated with significantly lower average blood pressures , earlier ECG normalization , less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension . Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability . In smokers the cardiac event rate was doubled . We propose that beta-blocker treatment effects depend on smoking status , with a significant interaction benefiting non-smoking men . Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events . Proportional hazards analysis also underlines the importance of other cardiovascular risk factors . The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in 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 AIM To determine if the management of a hypothetical case of essential hypertension by general practitioners conforms with the Report to the National Advisory Committee on Core Health and Disability Services guidelines on the Management of Raised Blood Pressure in New Zeal and ( Core Services Report on Hypertension ) sent to all general practitioners in November 1992 . METHOD A cross-sectional survey of a r and om sample of 100 Auckl and general practitioners using a st and ard case of a 60 year old man with essential hypertension . Seventy interviews were conducted by a face-to-face interview and 30 by telephone interview . The main outcome measures were . Initial choice of medication and levels at which blood pressure would require treatment . RESULTS Forty one percent of the interviewed doctors had read the Core Services report on hypertension . Fifty percent of the doctors indicated they would use the recommended first line antihypertensive medication ( ie , diuretic or beta blocker ) . Doctors who prescribed beta blockers had been graduated a significantly longer time than those who did not . The majority of doctors indicated that they would initiate pharmacological treatment at lower blood pressures in younger patients than older patients contrary to the recommendation of the report . CONCLUSIONS Current reported practice is only partially consistent with that suggested by the Core Services report on hypertension . Approximately half of the doctors interviewed were prescribing the recommended first line medication . Treatment was more likely to be initiated at lower levels in younger patients than in older patients in spite of the higher absolute risk and potential absolute benefit in the latter group . Adherence to the guidelines could see a shift from overtreatment of younger patients to an increase in treatment for older patients who are at higher risk of blood pressure related disease . More specific graduate educational measures will be needed if the Core Services report on hypertension are to be implemented A double-blind , positively controlled , forced dose titration study comparing the efficacy and safety of atenolol , captopril , and verapamil sustained release as single agents in the treatment of black patients with mild to moderate hypertension ( diastolic blood pressure , 95 to 114 mm Hg ) was conducted . A total of 394 patients were r and omized to one of the three therapies .  Mean blood pressures during a 2- to 4-week placebo treatment period ( baseline ) ranged from 100.4 to 100.7 mm Hg diastolic and 151.7 to 152.5 mm Hg systolic for the three groups . Of the patients , 355 ( of whom 345 had assessable data ) completed the first treatment period , which consisted of therapy with either 50 mg/d of atenolol , 25 mg every 12 hours of captopril , or 240 mg/d of verapamil sustained release . During the second 4-week treatment period , which 319 patients completed ( 307 assessable ) , half of the patients had their antihypertensive medication increased and the other half continued the same dose . Goal blood pressure was defined as a supine diastolic pressure of less than 90 mm Hg or a 10-mm Hg or greater drop in supine diastolic blood pressure from pretreatment levels . Atenolol , captopril , and verapamil sustained release therapy was associated with goal blood pressure achievement during the first treatment period 55.1 % , 43.8 % , and 65.2 % of the time , respectively , and during the second treatment period 59.6 % , 57.1 % , and 73.0 % of the time . Side effects were minimal and comparable for all three drugs 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 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 Two first‐line antihypertensive therapies for initiating treatment in hypertension were compared , the angiotensin‐converting enzyme inhibitor ( ACEI ) zofenopril and the beta‐blocker atenolol . The study was multi‐centre and double‐blind , and included 304 middle‐aged to elderly patients with mild to moderate hypertension who were r and omized to receive either zofenopril 30–60 mg once daily ( od ) or atenolol 50–100 mg od for 4 weeks with the possibility to an up‐titration in non‐responding patients . The higher dose level was then administered until 12 weeks after r and omization . Blood pressures ( BPs ) were substantially reduced by either treatment , but after 4 weeks , the systolic and diastolic BP reductions were significantly greater ( p<0.05 ) with zofenopril ( −15.6/−13.5 mmHg ) compared with atenolol ( −13.1/−11.8 mmHg ) . After 12 weeks and the possibility of dose up‐titration , BP differences between treatments were no longer significant . However , control rates ( sitting diastolic BP < 90 mmHg ) for zofenopril remained significantly higher compared with atenolol .  The number of subjects with adverse drug reactions possibly or probably related to the study medication was 14 ( 9.1 % ) in the zofenopril group and 30 ( 20.8 % ) in the atenolol group ( p = 0.008 ) . It is concluded that zofenopril as well as atenolol induces substantial reductions of diastolic BP in middle‐aged to elderly patients with hypertension . However , the control rate when initiating antihypertensive therapy with zofenopril is higher than that for atenolol Atenolol and bisoprolol , two beta-1-selective blockers , were compared in patients with mild and medium severe hypertension . Forty patients with a diastolic blood pressure of 95 - 115 mm Hg were two weeks after discontinuation of treatment divided at r and om into two groups treated with 50 mg atenolol and 5 mg bisoprolol . If the blood pressure was not affected by this dosage , the dose was raised to 100 mg atenolol and 10 mg bisoprolol . The blood pressure readings , heart rate , side effects of the drugs , laboratory and echocardiographic values were followed up for a period of three months . The authors recorded a marked decline of pressure and heart rate after the first week of therapy , the pressure readings in an upright position did not differ statistically from values in a sitting position , orthostatic hypotension was not recorded . The rate of success of bisoprolol was 85 % , of atenolol 75 % . During treatment no serious side-effects were observed . The biochemical parameters and echocardiographic values were not altered significantly by treatment . Atenolol and bisoprolol are two effective beta-1-selective blockers with a comparable effect in the treatment of mild and medium severe hypertension . They are useful in monotherapy as well as in combination with other antihypertensive drugs . In hypertension associated with diabetes mellitus , incipient bronchopulmonary disease and pregnancy they are also indicated . They are well tolerated also by elderly patients , an advantage of bisoprolol may be that it has a smaller impact on pressure and heart rate during the night OBJECTIVES The goal of this study was to determine if a low-dose combination of the angiotensin-converting enzyme inhibitor perindopril ( Per ) and the diuretic indapamide ( Ind ) reduces central ( thoracic aorta , carotid artery ) as well as brachial systolic blood pressure ( SBP ) more than the beta-blocker atenolol and to determine the hemodynamic factors influencing independently brachial and central SBP : pulse wave velocity ( PWV ) and pattern of wave reflections . BACKGROUND In high cardiovascular risk population s , angiotensin blockade improves survival without affecting brachial SBP and diastolic blood pressure ( DBP ) . Whether central SBP , which is physiologically lower than brachial SBP , is significantly reduced has never been investigated . METHODS This study was a double-blind r and omized trial for one year in patients with essential hypertension . RESULTS For a similar DBP reduction , Per/Ind decreased SBP significantly more than atenolol , with a more pronounced reduction for central than for brachial SBP . After one year , the difference between brachial and central SBP was maintained by Per/Ind ( 8.28 + /- 1.53 mm Hg ) and significantly attenuated by atenolol ( 0.29 + /- 1.61 mm Hg ) . Under atenolol , the principal factor modulating SBP reduction was mean blood pressure . Under Per/Ind , this parameter played a minor role , and the central SBP reduction implied a major role for disturbed PWV and wave reflections . CONCLUSIONS Under Per/Ind , but not atenolol , normalization of brachial SBP is achieved with a significantly greater reduction of central SBP . This hemodynamic profile reflects changes of wave reflections issued from distal arterial and arteriolar territory , where Per/Ind , but not atenolol , is known to improve vessel wall structure Abstract Amlodipine has potential advantages in children since it can be dissolved into a liquid preparation and has a long elimination half-life , allowing for once-daily administration . The objective of this study was to compare the efficacy and compliance of amlodipine with that of st and ard long-acting calcium channel blockers ( felodipine or nifedipine ) in hypertensive children . A r and omized , prospect i ve , crossover study of 11 hypertensive children ( 9–17 years of age , 10 renal transplant patients ) was performed with electronic monitoring of compliance . Each treatment arm was 30 days . No significant differences were observed in mean systolic ( SBP ) and diastolic blood pressures ( DBP ) between amlodipine and the other calcium channel blockers . Using 24-h blood pressure monitoring there were no significant differences over each drug treatment period in both mean day-time and night-time SBP and DBP . Patient compliance was similar in both the amlodipine and the nifedipine/felodipine treatment periods . These data suggest that amlodipine is as effective in pediatric nephrology patients as nifedipine and felodipine . Amlodipine may be optimally suited for treatment of young children because at present it is the only calcium channel blocker which can be administered once daily as a liquid preparation Background : Although the prevalence of hypertension ( HTN ) continues to increase in developing countries , including China , recent data are lacking . A nationwide survey was conducted from October 2012 to December 2015 to assess the prevalence of HTN in China . Methods : A stratified multistage r and om sampling method was used to obtain a nationally representative sample of 451 755 residents ≥18 years of age from 31 provinces in mainl and China from October 2012 to December 2015 .  Blood pressure ( BP ) was measured after resting for 5 minutes by trained staff using a vali date d oscillometric BP monitor .  HTN was defined as systolic BP ( SBP ) ≥140 mm Hg/or diastolic BP ( DBP ) ≥90 mm Hg or use of antihypertensive medication within 2 weeks . Pre-HTN was defined as SBP 120 to 139 mm Hg and DBP 80 to 89 mm Hg without antihypertensive medication  . HTN control was defined as SBP < 140 mm Hg and DBP<90 mm Hg . In addition , the prevalence of HTN ( SBP ≥130 or DBP ≥80 mm Hg ) and control rate ( SBP < 130 and DBP < 80 mm Hg ) of HTN were also estimated according to the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline . Results : Overall , 23.2 % ( ≈244.5 million ) of the Chinese adult population ≥18 years of age had HTN , and another 41.3 % ( ≈435.3 million ) had pre-HTN according to the Chinese guideline . There were no significant differences of HTN prevalence between urban and rural residents ( 23.4 % versus 23.1 % , P=0.819 ) . Among individuals with HTN , 46.9 % were aware of their condition , 40.7 % were taking prescribed antihypertensive medications , and 15.3 % had controlled HTN . Calcium channel blockers were the most commonly used antihypertensive medication ( 46.5 % ) as monotherapy , and 31.7 % of treated hypertensive patients used ≥2 medications . The prevalence of HTN based on the 2017 American College of Cardiology/American Heart Association guideline was twice as high as that based on 2010 Chinese guideline ( 46.4 % ) , whereas the control rate fell to 3.0 % . Conclusions : In China , there is a high prevalence of HTN and pre-HTN , and awareness , treatment , and control of HTN were low . Management of medical therapy for HTN needs to improve Hypertensive African Americans often respond poorly to beta-blocker monotherapy , compared with whites . There is evidence , however , that suggests that this response may be different if beta-blockers with vasodilating effects are used . This 12-week , multi-center , double-blind , r and omized placebo-controlled study assessed the antihypertensive efficacy and safety of nebivolol , a cardioselective , vasodilating beta1-blocker , at doses of 2.5 , 5 , 10 , 20 , or 40 mg once daily in 300 African American patients with stage I or II hypertension ( mean sitting diastolic blood pressure [ SiDBP ] > or = 95 mm Hg and < or = 109 mm Hg ) . The primary efficacy end point was the baseline-adjusted change in trough mean SiDBP . After 12 weeks , nebivolol significantly reduced least squares mean SiDBP ( P < or = .004 ) at all doses of 5 mg and higher and sitting systolic blood pressure ( P < or = .044 ) at all doses 10 mg and higher , compared with placebo . The drug was safe and well-tolerated , with no significant difference in the incidence of adverse events compared with placebo . Nebivolol monotherapy provides antihypertensive efficacy , with few significant adverse effects , in hypertensive African Americans OBJECTIVES To evaluate if magnesium alters blood pressure in hypertensive patients treated with beta blockers and if such effect can be coupled to a change in potassium and magnesium levels in muscle , serum and urine . DESIGN A r and omized double-blind , cross-over study with magnesium and placebo taken orally , each for 8 weeks . SETTING Outpatient clinic , University Hospital , Umeå , Sweden . SUBJECTS Thirty-nine patients aged 26 - 69 years with moderate essential hypertension , treated before entry and during the study with continuous , unchanged beta blockers completed the study . INTERVENTIONS R and om allocation to receive magnesium aspartate or placebo . Daily magnesium dose was 15 mmol ( 365 mg ) distributed three times a day over 8 weeks . MAIN OUTCOME MEASURES Blood pressure , serum , urine and muscle magnesium and potassium . Measurements performed at the start , after 8 and 16 weeks . RESULTS Systolic supine and st and ing blood pressure significantly decreased when magnesium was supplemented following placebo but not when magnesium was given at start . When magnesium and placebo groups were independently compared there was no significant change in supine and st and ing systolic and diastolic pressure . Serum and urine magnesium and serum potassium were significantly higher after magnesium treatment , whilst no change was present in urine potassium or in muscle magnesium and potassium . CONCLUSIONS This study showed that 15 mmol magnesium day-1 given to mild to moderate hypertensive patients treated with beta blockers could be the cause of a significant decrease in supine and st and ing systolic blood pressure
When the blood pressure lowering effect of beta-blockers from this review was compared to that of thiazide diuretics from our previous review ( Chen 2009 ) , second-line beta-blockers reduce systolic BP to the same extent as second-line thiazide diuretics , but reduce diastolic BP to a greater degree .
The different effect on diastolic BP means that beta-blockers have little or no effect on pulse pressure whereas thiazides cause a significant dose-related decrease in pulse pressure .
This difference in the pattern of BP lowering with beta-blockers as compared to thiazides might be the explanation for the fact that beta-blockers appear to be less effective at reducing adverse cardiovascular outcomes than thiazide diuretics , particularly in older individuals
BACKGROUND Beta-blockers are one of the more commonly prescribed classes of anti-hypertensive drugs , both as first-line and second-line .
OBJECTIVES To quantify the effect on systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , heart rate and withdrawals due to adverse effects of beta-blocker therapy when given as a second-line drug in adult patients with primary hypertension .