Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension. Combination of a thiazide, a vasodilator and reserpine compared with methyldopa plus hydrochlorothiazide in the treatment of hypertension in Zimbabwe. The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group. Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension Controlled-release carvedilol in the treatment of essential hypertension. The Felodipine Event Reduction (FEVER) Study: a randomized long-term placebo-controlled trial in Chinese hypertensive patients Differential time effect profiles of amlodipine, as compared to valsartan, revealed by ambulatory blood pressure monitoring, self blood pressure measurements and dose omission protocol. A comparison of the efficacies and duration of action of the angiotensin II receptor blockers telmisartan and amlodipine. Blood Pressure and Cardiovascular Disease Risk in the Veterans Affairs Diabetes Trial An ambulatory blood pressure monitoring study of the comparative antihypertensive efficacy of two angiotensin II receptor antagonists, irbesartan and valsartan Candesartan and hydrochlorothiazide in isolated systolic hypertension Antihypertensive efficacy and safety of olmesartan medoxomil and ramipril in elderly patients with mild to moderate essential hypertension: the ESPORT study Resistant arterial hypertension and hyperlipidemia: atorvastatin, not vitamin C, for blood pressure control. Effect of Low-Dose Manidipine on Ambulatory Blood Pressure in Very Elderly Hypertensives Reserpine plus hydrochlorothiazide and sotalol plus hydrochlorothiazide in Black and Indian hypertensive patients. Comparative effects of candesartan cilexetil and losartan in patients with systemic hypertension. Candesartan Versus Losartan Efficacy Comparison (CANDLE) Study Group. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. Effect of atenolol and reserpine on selected events in the systolic hypertension in the elderly program (SHEP). Felodipine extended release in mild to moderate hypertension. Relationship of Antihypertensive Treatment Regimens and Change in Blood Pressure to Risk for Heart Failure in Hypertensive Patients Randomly Assigned to Doxazosin or Chlorthalidone: Further Analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial Aliskiren, a Novel Oral Renin Inhibitor, Provides Dose-Dependent Efficacy and Placebo-Like Tolerability in Japanese Patients with Hypertension Efficacy of a Very‐low‐dose Combination of Perindopril and Indapamide—Preterax Compared with Cilazapril Monotherapy in Patients with Inadequate Blood Pressure Control—A Randomized, Double‐blind, Add‐on Study
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 OBJECTIVE To compare the effectiveness of the combination of hydrochlorothiazide ( HCT ) plus sustained-release nifedipine with the combination of HCT plus reserpine in lowering  high blood pressure ( BP )  unresponsive to HCT monotherapy . DESIGN An open , r and omised crossover drug trial . SETTING Out patients ' clinic in Parirenyatwa Hospital , Harare , a tertiary referral centre . SUBJECTS 32 Black patients of both sexes with newly diagnosed or previously treated hypertension aged between 21 and 65 years who had a BP > 140/95 after receiving HCT 25 mg daily for four weeks were studied . INTERVENTION Patients were kept on HCT 25 mg daily and were r and omised to receive either reserpine 0.25 mg daily or nifedipine ( Adalat Retard ) 20 mg bd for four weeks . This was followed by a two week washout period during which patients received HCT 25 mg daily only . After the washout period patients were crossed over to the alternative treatment for four weeks . Patients were kept on HCT 25 mg daily throughout the trial . MAIN OUTCOME MEASURES The main outcome measure was the fall in BP which was taken as the difference between the BP at baseline and the BP at the end of each treatment period . Both systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) measurements were taken . RESULTS Both second line drugs were effective in lowering SBP and DBP and there was no significant difference between them . Nifedipine reduced SBP by 18.9 mmHg ( 95 % CI 12.1 to 25.7 ) and DBP by 9.6 mmHg ( 95 % CI 7.2 to 12.0 ) . Reserpine reduced SBP by 15.9 mmHg ( 95 % CI 8.4 to 23.4 ) and DBP by 11.1 mmHg ( 95 % CI 7.5 to 14.6 ) . However , only two patients attained the target DBP of < or = 90 mmHg after each active treatment period . CONCLUSION AND RECOMMENDATIONS Since both agents were equally effective in reducing both SBP and DBP and reserpine is much cheaper than nifedipine , it is recommended that for a developing country like Zimbabwe , the combination of HCT and reserpine at the above doses should be used as the first step to treat mild to moderate hypertension without evidence of end organ damage . However , further trials should compare BP lowering effects as well as end organ protection offered by the trial drugs Brinerdin ( S and oz ) , a combination of a diuretic ( clopamide 5 mg ) , a vasodilator ( dihydro-ergocristine 0.5 mg ) and reserpine ( 0.1 mg ) ( CDR ) was compared with methyldopa ( MD ) plus hydrochlorothiazide ( HCT ) for antihypertensive effect , adverse reactions , compliance and patient preference in an open cross-over trial . Eighteen patients completed both arms of the trial and 5 patients who completed the CDR arm were withdrawn while on the MD arm because of adverse effects in 4 and poor control in 1 . On HCT 50 mg daily the mean baseline systolic blood pressure was 163.9 + /- 16.3 mmHg and the diastolic blood pressure was 105.9 + /- 6.7 mmHg . On CDR these were reduced to systolic blood pressure 140.3 + /- 15.1 mmHg and diastolic blood pressure 87.8 + /- 9.3 mmHg . On MD + HCT the systolic blood pressure was reduced to 138.5 + /- 16.9 mmHg and the diastolic blood pressure to 88.9 + /- 10.3 mmHg . The differences between the two treatment periods in systolic blood pressure ( 1.8 mmHg ; 95 % confidence interval ( CI ) - 4.1 + 7.7 mmHg ) and diastolic blood pressure ( 1.1 mmHg ; 95 % CI - 4.6 + 2.4 mmHg ) were not significant with P values of 0.6 and 0.7 respectively . Compliance was 98.2 % for CDR and 94.7 % for MD + HCT ( P = 0.02 ) . Unusual sleepiness occurred more frequently in the MD arm ( P less than 0.01 ) . Thirteen patients chose to continue on CDR , 2 on MD + HCT and 3 had no preference ( P = 0.005 ) . CDR is similar in antihypertensive effect to MD + HCT but is better tolerated with fewer withdrawals , fewer adverse effects , better compliance and has more patients electing to continue taking it The Systolic Hypertension in the Elderly Program ( SHEP ) is a r and omized double-blind placebo-controlled trial to determine if antihypertensive treatment of isolated systolic hypertension ( ISH ) [ systolic blood pressure ( SBP ) greater than or equal to 160 mmHg , diastolic blood pressure ( DBP ) less than 90 mmHg ] reduces the 5 year incidence of fatal and nonfatal stroke . Between March 1 , 1985 and January 15 , 1988 , 4736 persons ( target 4800 ) with ISH , age 60 years and over , were enrolled . Potential participants met blood pressure ( BP ) and age criteria . Those on antihypertensive medication prior to enrollment without documented diastolic hypertension had their medication tapered and discontinued , and then met BP criteria ( 33 % of cohort ) . Stepped-care therapy with chlorthalidone and atenolol ( alternative , reserpine ) or matching placebos was initiated as first and second steps . At baseline the trial population was 43.1 % male , 56.9 % female ; 13.9 % black , 86.1 % non-black . Also , the mean age was 71.6 years ; the mean SBP was 170.3 mmHg and the mean DBP was 76.6 mmHg ; 59.8 % had codeable resting electrocardiographic abnormalities .  The trial is now in follow-up phase with scheduled termination in 1991 The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents . This r and omized , double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate ( amlodipine ) in subjects with mild-to-moderate hypertension . Following a 4-week , single-blind , placebo run-in period , 440 subjects aged ⩾18 years were r and omized to the starting dose of olmesartan medoxomil ( 20 mg/day ) , amlodipine ( 5 mg/day ) , or placebo for 8 weeks . Subjects were evaluated by  24-h ambulatory blood pressure monitoring ( ABPM ) and by seated cuff blood pressure ( BP ) measurements at trough . The primary end point was the change from baseline in mean 24-h diastolic blood pressure ( DBP ) by ABPM at Week 8 . Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure ( SBP ) at 8 weeks , change from baseline in mean seated trough cuff DBP and SBP measurements , and response and control rates for DBP < 90 and < 85 mmHg . Control rates for SBP < 140 and < 130 mmHg were also calculated . Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo . Mean reductions in ambulatory and seated BP were similar between the two active agents ; however , in the olmesartan medoxomil group , significantly more patients achieved the SBP goal of < 130 mmHg and the DBP goal of < 85 mmHg . Both drugs were well tolerated at the recommended starting dose . Although amlodipine was associated with a higher incidence of oedema , this did not reach statistical significance . Olmesartan medoxomil is an effective antihypertensive agent , with BP-lowering efficacy at the starting dose similar to that of amlodipine , and is associated with more patients achieving the rigorous BP goals of SBP < 130 mmHg and DBP < 85 mmHg 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 Objective To compare the incidence of stroke and other cardiovascular events in hypertensive patients receiving a low-dose diuretic and low-dose calcium antagonist combination with those receiving low-dose diuretic monotherapy  , and assess the effects of a small blood pressure difference at achieved levels lower than those achieved in previous placebo-controlled trials . Methods The Felodipine Event Reduction ( FEVER ) trial was an investigator- design ed , prospect i ve , multicentre , double-blind , r and omized , placebo-controlled , parallel group trial . It enrolled 9800 Chinese patients , of either sex , aged 50–79 years , with one or two additional cardiovascular risk factors or disease , whose blood pressure , 6 weeks after switching from previous antihypertensive therapy to low-dose ( 12.5 mg a day ) hydrochlorothiazide , was in the range 140–180 mmHg ( systolic ) or 90–100 mmHg ( diastolic ) . These patients were r and omly assigned either to low-dose felodipine extended release or placebo , and followed at 3-month intervals for an average of 40 months . Results The intention-to-treat analysis included 9711 r and omly selected patients with only 30 ( 0.3 % ) lost to follow-up . A total of 31 842 patient-years of follow-up were accumulated , with 85.9 % of patients remaining on blinded r and omized treatment . Add-on therapy was given to 33.9 % of the hydrochlorothiazide – felodipine patients and to 42.3 % of the hydrochlorothiazide – placebo patients . In the felodipine  group , systolic blood pressure (SBP)/diastolic blood pressure ( DBP ) decreased ( from r and omization to study end ) from 154.2/91.0 to 137.3/82.5 mmHg , and in the placebo group from 154.4/91.3 to 142.5/85.0 mmHg , with an average difference throughout the trial of 4.2/2.1 mmHg . In the felodipine group , the primary endpoint ( fatal and non-fatal stroke ) was reduced by 27 % ( P = 0.001 ) . Among secondary endpoints , all cardiovascular events were reduced by 27 % ( P < 0.001 ) , all cardiac events by 35 % ( P = 0.012 ) , death by any cause by 31 % ( P = 0.006 ) , coronary events by 32 % ( P = 0.024 ) , heart failure by 30 % ( P = 0.239 ) , cardiovascular death by 33 % ( P = 0.019 ) , cancer by 36 % ( P = 0.017 ) in the felodipine group . No significant differences were found in new-onset diabetes . Both treatments were very well tolerated . Conclusions In moderately complicated hypertensive patients from China even a difference in SBP/DBP as small as 4/2 mmHg , such as that induced by adding low-dose felodipine to low-dose hydrochlorothiazide , is associated with very substantial reductions in the incidence of most types of cardiovascular events . As the SBP achieved in the felodipine group was below the recommended goal of less than 140 mmHg , and SBP in the placebo group was slightly above that level , FEVER provides the required evidence in support of the guidelines recommended goal , even for a hypertensive population not entirely consisting of patients with diabetes or previous cardiovascular events Amlodipine and valsartan are once-daily antihypertensive agents . To date , no comparison between these agents given as monotherapies was reported . This study was aim ed to evaluate the therapeutic coverage and safety of amlodipine and valsartan in mild-to-moderate hypertensive patients . Multicenter , double-blind , r and omized , comparative study . After a 4-week placebo wash-out period , 246 out patients with office diastolic blood pressure 95 < or = DBP < or = 110 mmHg and systolic blood pressure ( SBP ) < 180 mmHg , in addition to a mean daytime SBP and /or DBP > 135/85 mmHg on 24-h ambulatory blood pressure monitoring ( ABPM ) , were r and omly allocated to once-daily amlodipine 5 - 10 mg or valsartan 40 - 80 mg , for 12 weeks . In a subgroup of patients , 48-h ABPM were performed at the end of the treatment period . Dose omission was simulated by a single-blind placebo dosing . The primary efficacy end-point was the 24-h trough office BP after 12 weeks of active therapy . The reductions in 24-h trough BP were more pronounced in amlodipine compared with valsartan group as well in office [ SBP : -17.8 + /- 10.9 vs. -14.6 + /- 11.2 , P = 0.025 , DBP : -12.7 + /- 7.2 vs. -10.9 + /- 7.8 mmHg , P = 0.06 ) as in ambulatory BP ( SBP/DBP : -13.0 + /- 13.7/-10.8 + /- 9.1 vs. -7.2 + /- 19.4/-4.9 + /- 13.4 mmHg , P < 0.05 ) . Forty-eight hours after the last active dose , the slope of the morning BP surge ( 4 - 9 h ) was less steep with amlodipine vs. valsartan [ DBP ( P < 0.04 ) , SBP ( n.s . ) ] . Ankle edema were more often reported in amlodipine group . These results suggest a superior BP lowering and a longer duration of action with amlodipine compared with valsartan OBJECTIVES : To compare the antihypertensive effects and duration of action of the angiotensin II receptor antagonist , telmisartan , amlodipine , and placebo in patients with mild-to-moderate hypertension using both conventional clinic blood pressures and ambulatory blood pressure monitoring ( ABPM ) . METHODS : After a 4-week single-blind , placebo run-in period , qualifying patients were r and omly allocated in double-blind manner to be administered 40 mg telmisartan ( n = 73 ; increased to 80 and 120 mg as necessary for patients whose diastolic blood pressure ( DBP ) remained > 90 mmHg ) ; 5 mg amlodipine ( n = 78 ; titrated to 5 mg and titrated to 10 mg for patients whose DBP remained > 90 mmHg ) ; or placebo ( n = 81 ) . ABPM was performed at the end of the baseline period and again at the end of 12 weeks of double-blind treatment . RESULTS : Telmisartan and amlodipine treatments significantly decreased trough supine systolic blood pressure and DBP ( P < 0.001 , measured conventionally ) to a similar extent ( by 13.1/7.1 and 14.0/7.1 mmHg , respectively , at the end of 12 weeks ' treatment ) compared with placebo . Both drugs also significantly reduced 24 h mean systolic blood pressures and DBP compared with placebo ( P < 0.0001 ) , measured using ABPM , maintaining control of blood pressure throughout the dosing period . Reductions in DBP with telmisartan were greater ( P < 0.05 ) than those with amlodipine during the night-time interval and the last 4 h of the dosing period . Twenty-four-hour mean ABPM DBP < 85 mmHg were observed in 71 % of telmisartan patients and in 55 % of patients administered amlodipine . In addition , heart rates in patients treated with telmisartan were lower than heart rates in those treated with amlodipine during the final 4 h of the dosing period ( P = 0.0003 ) and during the morning interval ( P = 0.005 ) . Generally , both telmisartan and amlodipine were well tolerated , however , drug-related edema occurred significantly more commonly ( P < 0.05 ) among the patients administered amlodipine than it did among patients administered either telmisartan or placebo . CONCLUSIONS : Clinic blood pressure measurements detected no difference between the antihypertensive effects and duration s of action of telmisartan and amlodipine , both agents producing statistically significant reductions compared with placebo . ABPM measurements , however , revealed differences between the efficacies at specific time points within the dosing periods . These findings highlight the potential importance of the use of ABPM for evaluating and comparing efficacies of antihypertensive agents OBJECTIVE Blood pressure ranges associated with cardiovascular disease ( CVD ) events in advanced type 2 diabetes are not clear . Our objective was to determine whether baseline and follow-up ( On- Study ) systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , and SBP combined with DBP predict CVD events in the Veterans Affairs Diabetes Trial ( VADT ) . RESEARCH DESIGN AND METHODS Participants in the VADT ( n = 1,791 ) with hypertension received stepped treatment to maintain blood pressure below the target of 130/80 mmHg in st and ard and intensive glycemic treatment groups .  Blood pressure levels of all subjects at baseline and On- Study were analyzed to detect associations with CVD risk . The primary outcome was the time from r and omization to the first occurrence of myocardial infa rct ion , stroke , congestive heart failure , surgery for vascular disease , inoperable coronary disease , amputation for ischemic gangrene , or CVD death . RESULTS Separated SBP ≥140 mmHg had significant risk at baseline ( hazards ratio [ HR ] 1.508 , P < 0.001 ) and On- Study ( HR 1.469 , P = 0.002 ) . DBP < 70 mmHg increased CVD events at baseline ( HR 1.482 , P < 0.001 ) and On- Study ( HR 1.491 , P < 0.001 ) . Combined blood pressure categories indicated high risk for CVD events for SBP ≥140 with DBP < 70 mmHg at baseline ( HR 1.785 , P = 0.03 ) and On- Study ( HR 2.042 , P = 0.003 ) and nearly all SBP with DBP < 70 mmHg . CONCLUSIONS Increased risk of CVD events with SBP ≥140 mmHg emphasizes the urgency for treatment of systolic hypertension . Increased risk with DBP < 70 mmHg , even when combined with SBP in guideline -recommended target ranges , supports a new finding in patients with type 2 diabetes . The results emphasize that DBP < 70 mmHg in these patients was associated with elevated CVD risk and may best be avoided Background The primary objective of this study was to compare the change from baseline in mean diastolic ambulatory blood pressure ( ABP ) at 24 h post dose ( trough measurement ) after 8 weeks of treatment with irbesartan or valsartan in subjects with mild-to-moderate hypertension . Secondary objectives included comparing the mean changes from baseline in systolic ABP at trough ; 24-h ABP ; morning and night-time ABP ; self-measured systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) ; and office-measured SBP and DBP at trough . Design After a 3-week , single blind , placebo lead-in period , 426 subjects were r and omized to receive either irbesartan 150 mg or valsartan 80 mg for 8 weeks . Methods Ambulatory blood pressure measurements were obtained at baseline and at week 8 . Self-measured morning and evening DBP and SBP readings were obtained at home over a 7-day period at baseline and at week 8 . Office-measured seated DBP and SBP measurements were obtained at trough , at baseline , and at week 8 . Results Irbesartan demonstrated significantly greater reductions than valsartan for mean change from baseline in diastolic ABP at trough ( −6.73 versus −4.84 mmHg , respectively;P = 0.035 ) . Irbesartan produced significantly greater reductions than valsartan for mean systolic ABP at trough ( −11.62 versus −7.5 mmHg , respectively;P < 0.01 ) and for mean 24-h diastolic ABP ( −6.38 versus −4.82 mmHg , respectively;P = 0.023 ) and systolic ABP ( −10.24 versus −7.76 mmHg;P < 0.01 ) . Irbesartan also produced significantly greater reductions than valsartan for office-measured seated DBP ( −10.46 versus 7.28 mmHg , respectively;P < 0.01 ) and SBP ( −16.23 versus −9.96 mmHg , respectively;P < 0.01 ) and for self-measured morning DBP ( −6.28 versus −3.75 mmHg , respectively;P < 0.01 ) and SBP ( −10.21 versus −6.97 mmHg , respectively;P < 0.01 ) . Both drugs were well tolerated . Conclusion Irbesartan was more effective than valsartan in reducing DBP and SBP at trough and in providing greater overall 24-h blood pressure-lowering efficacy Aim : We investigated the efficacy and safety of daily c and esartan 8/16 mg and hydrochlorothiazide 12.5 mg as monotherapy and in combination in older patients with systolic hypertension . Methods : The study used a double-blind r and omized placebo-controlled crossover design . Treatment phases were of 6 weeks duration . For inclusion , patients were aged 55 - 84 years with sitting systolic blood pressure ( SBP ) 160 - 210 mmHg and diastolic blood pressure ( DBP ) < 95 mmHg . Nineteen patients ( 11 male , eight female , median age 68 years ) completed the study . Major findings : Compared with the placebo phase , clinic and ambulatory SBP was significantly reduced with both dose-adjusted c and esartan and fixed-dose hydrochlorothiazide as monotherapy , the effect of c and esartan being greater than that of hydrochlorothiazide . In combination , the effects of the two drugs were additive . Both drugs were well tolerated either as monotherapy or in combination . Conclusion : Both c and esartan and a low dose of hydrochlorothiazide are effective and well-tolerated antihypertensive agents in isolated systolic hypertension with additive effects in combination . C and esartan was more effective than hydrochlorothiazide , although it is possible that dose adjustment only of c and esartan could have enhanced its relative effectiveness Objective To compare the efficacy and safety of the angiotensin II antagonist olmesartan medoxomil ( O ) and the ACE inhibitor ramipril ( R ) in elderly patients with essential arterial hypertension . Methods After a 2-week placebo wash-out 1102 treated or untreated elderly hypertensive patients aged 65–89 years ( office sitting diastolic blood pressure , DBP , 90–109 mmHg and /or office sitting systolic blood pressure , SBP , 140–179 mmHg ) were r and omized double-blind to 12-week treatment with O 10 mg or R 2.5 mg once-daily . After the first 2 and 6 weeks doses could be doubled in non-normalized [ blood pressure ( BP ) < 140/90 mmHg for nondiabetic and < 130/80 mmHg for diabetic ) individuals , up to 40 mg for O and 10 mg for R. Office BPs were assessed at r and omization , after 2 , 6 and 12 weeks of treatment , whereas 24-h ambulatory BP was recorded at r and omization and after 12 weeks . Results In the intention-to-treat population ( 542 patients O and 539 R ) after 12 weeks of treatment baseline-adjusted office SBP and DBP reductions were greater ( P < 0.01 ) with O [ 17.8 ( 95 % confidence interval : 16.8/18.9 ) and 9.2 ( 8.6/9.8 ) mmHg ] than with R [ 15.7 ( 14.7/16.8 ) and 7.7 ( 7.1/8.3 ) mmHg ] . BP normalization rate was also greater under O ( 52.6 vs. 46.0 % R , P < 0.05 ) . In the subgroup of patients with valid ambulatory BP recording ( 318 O and 312 R ) the reduction in 24-h average BP was larger ( P < 0.05 ) with O [ SBP : 11.0 ( 12.2/9.9 ) and DBP : 6.5 ( 7.2/5.8 ) mmHg ] than with R [ 9.0 ( 10.2/7.9 ) and 5.4 ( 6.1/4.7 ) mmHg ] . The larger blood pressure reduction obtained with O was particularly evident in the last 6 h from the dosing interval ; a better homogeneity of the 24-h BP control with O was confirmed by higher smoothness indices . The proportion of patients with drug-related adverse events was comparable in the two groups ( 3.6 O vs. 3.6 % R ) , as well as the number of patients discontinuing study drug because of a side effect ( 14 O vs. 19 R ) . Conclusion In elderly patients with essential arterial hypertension O provides an effective , prolonged and well tolerated BP control , representing a useful option among first-line drug treatments of hypertension in this age group BACKGROUND Hypertension is considered resistant if blood pressure can not be reduced to < 140/90 mmHg with an appropriate triple-drug regimen , including an oral diuretic , with all agents administered at maximal dosages . This definition has evolved with the development of new therapies and evidence -based data supporting treatment to lower BP goals . OBJECTIVE To assess whether vitamin C and atorvastatin improve endothelial function and blood pressure control in subjects with resistant arterial hypertension and dyslipidemia . METHODS Forty-eight hyperlipidemic subjects with RH ( office systolic BP > 140 mmHg and /or office diastolic BP > 90 mmHg notwithst and ing antihypertensive treatment with three medications in maximal doses ) were r and omized into three groups to receive additional medication for 8 weeks . Group VTC ( n = 17)--mean 24 hour SBP 150.6 + /- 5.2 mmHg , DBP 86.1 + /- 3.3 mmHg , low density lipoprotein 158.1 + /- 24.5 mg/dl -- received vitamin C 500 mg per day ; Group ATR ( n = 15)--mean 24 hour SBP 153.1 + /- 4.8 mmHg , DBP 87.1 + /- 6.7 mmHg , LDL 162.6 + /- 13.6 mg/dl -- received atorvastatin 20 mg/day ; and Group PLA ( n = 16)--mean 24 hour SBP 151.1 + /- 7.4 mmHg , DBP 84.8 + /- 5.9 mmHg , LDL 156.7 + /- 26.1 mg/dl -- received a placebo . High resolution ultrasound was used to calculate brachial artery flow-mediated dilation , and 24 hour ambulatory BP monitoring was performed at study entry and after 8 weeks . RESULTS In the ATR group there were significant reductions of SBP ( deltaSBP1 - 2 : 13.7 + /- 5.6 mmHg , P 0.001 ) , DBP ( deltaDBP1 - 2 : 7.8 + /- 5.7 mmHg , P 0.01 ) , LDL ( deltaLDL1 - 2 : 67.7 + /- 28.3 mg/dl , P < 0.001 ) and improvement of brachial artery FMD ( deltaFMD2 - 1 : 4.2 + /- 2.6 % ) . No significant changes in BP , LDL and FMD were observed in the other two groups . CONCLUSIONS In subjects with RH and dyslipidemia , atorvastatin 20 mg/day compared to vitamin C 500 mg/day may help to achieve better BP control and improve endothelial function in a finite period . A larger trial is needed to assess the drug 's efficacy in this population for longer periods Summary . To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure ( BP ) and heart rate ( HR ) in very elderly hypertensive patients , 54 patients aged 76–89 years ( mean age 81.8 years ) with systolic blood pressure ( SBP ) > 160 mmHg and diastolic blood pressure ( DBP ) > 90 mmHg were studied . After a 4-week placebo washout period , patients were r and omized to receive manidipine 10 mg or placebo , both administered once daily for 8 weeks . Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter . At each visit casual BP and HR were measured . At the end of the placebo period and after 8 weeks of active treatment , noninvasive 24-hour ambulate blood pressure measurement ABPM was performed . Manidipine significantly lowered casual sitting and st and ing SBP ( P < 0.001 ) and DBP ( P < 0.001 ) at the trough level . ABPM showed a significant decrease in 24-hour SBP and DBP values ( P < 0,001 ) , daytime SBP and DBP ( P < 0.001 ) , and night-time SBP ( P < 0.001 ) and DBP ( P < 0.005 ) . In addition , ABPM confirmed a consistent antihypertensive activity throughout the 24-hour dosing interval , without effect on the circadian BP profile . The trough/peak ratio was 0.67 for SBP and 0.59 DBP . No statistically significant change in HR was observed . The treatment was well tolerated , and there were no serious side effects . In conclusion , in very elderly hypertensive patients , once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP Fifty patients ( 25 Blacks and 25 Indians ) suffering from mild-to-moderate hypertension ( supine diastolic blood pressure 100 - 105 mmHg ) were studied in order to compare the antihypertensive effect of a combination of a beta-blocker ( sotalol hydrochloride 160 mg/d ) plus a thiazide derivative ( hydrochlorothiazide 25 mg/d ) ( Sotazide ; B-M ) with that of a combination of reserpine 0,1 mg/d ( Serpasil ; Ciba ) plus hydrochlorothiazide 25 mg/d ( Dichlotride ; Frosst MSD ) . The combination of reserpine plus hydrochlorothiazide was found to be as effective as that of sotalol plus hydrochlorothiazide in lowering the blood pressure in both the Black and the Indian patients . Two patients taking the combination containing reserpine developed side-effects , but this did not occur in any of those taking the combination containing sotalol . We feel that in developing countries , where the cost of therapy is important , reserpine in a dosage of less than 0,1 mg/d plus a thiazide derivative in low dosage is preferable to a beta-blocker plus a thiazide derivative in the treatment of hypertension The antihypertensive efficacy and tolerability of the novel angiotensin-II ( A-II ) receptor blocker c and esartan cilexetil and the prototype A-II receptor blocker , losartan , were compared in an 8-week , multicenter , double-blind , r and omized , parallel-group , titration-to-effect study of 332 adults ( 42 % women , 12 % black ) with systemic hypertension ( sitting diastolic blood pressure [ DBP ] 95 - 114 mmHg , inclusive ) . In patients with a mean trough ( 24 + /- 3 hours after dose ) sitting DBP of 90 mmHg or higher after 4 weeks of once daily administration of c and esartan 16 mg or losartan 50 mg , dose was titrated up to c and esartan 32 mg or losartan 100 mg once daily . The c and esartan regimen was significantly more effective than the losartan regimen in reducing trough sitting DBP at week 8 ( 11.0 mmHg versus 8.9 mmHg ) . C and esartan also produced numerically greater reductions in secondary blood pressure parameters , including sitting systolic blood pressure ( SBP ) , trough st and ing DBP and SBP , and peak ( 6 + /- 2.5 hours after dose ) sitting and st and ing DBP and SBP . Responder rates ( sitting DBP < 90 mmHg or reduction in blood pressure of > or = 10 mmHg ) and control rates ( sitting DBP < 90 mmHg ) were higher with c and esartan ( 64 % versus 54 % and 54 % versus 43 % , respectively ) . A total of 1.9 % of the patients taking c and esartan and 6.5 % of those taking losartan discontinued prematurely because of adverse events or lack of efficacy CONTEXT Despite evidence of efficacy of antihypertensive agents in treating hypertensive patients , safety and efficacy of antihypertensive agents for coronary artery disease ( CAD ) have been discerned only from subgroup analyses in large trials . OBJECTIVE To compare mortality and morbidity outcomes in patients with hypertension and CAD treated with a calcium antagonist strategy ( CAS ) or a non-calcium antagonist strategy ( NCAS ) .  DESIGN , SETTING , AND PARTICIPANTS R and omized , open label , blinded end point study of 22 576 hypertensive CAD patients aged 50 years or older , which was conducted September 1997 to February 2003 at 862 sites in 14 countries . INTERVENTIONS Patients were r and omly assigned to either CAS ( verapamil sustained release ) or NCAS ( atenolol ) . Strategies specified dose and additional drug regimens . Tr and olapril and /or hydrochlorothiazide was administered to achieve blood pressure goals according to guidelines from the sixth report of the Joint National Committee on Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC VI ) of less than 140 mm Hg ( systolic ) and less than 90 mm Hg ( diastolic ) ; and less than 130 mm Hg ( systolic ) and less than 85 mm Hg ( diastolic ) if diabetes or renal impairment was present . Tr and olapril was also recommended for patients with heart failure , diabetes , or renal impairment . MAIN OUTCOME MEASURES Primary : first occurrence of death ( all cause ) , nonfatal myocardial infa rct ion , or nonfatal stroke ; other : cardiovascular death , angina , adverse experiences , hospitalizations , and blood pressure control at 24 months . RESULTS At 24 months , in the CAS group , 6391 patients ( 81.5 % ) were taking verapamil sustained release ; 4934 ( 62.9 % ) were taking tr and olapril ; and 3430 ( 43.7 % ) were taking hydrochlorothiazide . In the NCAS group , 6083 patients ( 77.5 % ) were taking atenolol ; 4733 ( 60.3 % ) were taking hydrochlorothiazide ; and 4113 ( 52.4 % ) were taking tr and olapril . After a follow-up of 61 835 patient-years ( mean , 2.7 years per patient ) , 2269 patients had a primary outcome event with no statistically significant difference between treatment strategies ( 9.93 % in CAS and 10.17 % in NCAS ; relative risk [ RR ] , 0.98 ; 95 % confidence interval [ CI ] , 0.90 - 1.06 ) . Two-year blood pressure control was similar between groups . The JNC VI blood pressure goals were achieved by 65.0 % ( systolic ) and 88.5 % ( diastolic ) of CAS and 64.0 % ( systolic ) and 88.1 % ( diastolic ) of NCAS patients . A total of 71.7 % of CAS and 70.7 % of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg . CONCLUSION The verapamil-tr and olapril-based strategy was as clinical ly effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients The effect of atenolol and reserpine on incidence of strokes , coronary heart disease ( CHD ) , cardiovascular disease ( CVD ) , and mortality  was assessed in 4736 persons aged 60 years and older with isolated systolic hypertension . Participants were r and omized to either chlorthalidone ( 2371 ) , with step-up to atenolol , or reserpine if needed , or placebo ( 2365 ) . The average baseline SBP/DBP was 170/77 mm Hg . In the active treatment group , step 1 , dose 1 was chlorthalidone , 12.5 mg/day ; dose 2 was 25 mg/day . For step 2 , dose 1 was atenolol 25 mg/day ( or reserpine 0.05 mg/day if atenolol was contraindicated ) ; dose 2 was 50 mg/day ( reserpine , 0.10 mg/day ) . During 4.5 years average follow-up , 32 % ( 757 ) of the active treatment group were on atenolol , with an average exposure of two years and 8 % ( 193 ) were on reserpine with an average exposure of 1.7 years . Overall there were 96 strokes , 140 CHD events and 289 CVD events among the 2365 active group participants . Using time-dependent lifetable regression with adjustment for several variables , the addition of either atenolol or reserpine to chlorthalidone did not substantially alter the risk ratios for chlorthalidone alone . The relative risk for CHD events for atenolol versus no atenolol was 1.04 ( 95 % confidence interval : 0.58 , 1.86 ) and for reserpine versus no reserpine was 0.93 ( 95 % confidence interval : 0.29 , 2.96 ) . The relative risk for atenolol  were 0.84 ( 95 % confidence interval : 0.54 , 1.30 ) for death , 1.34 ( 95 % confidence interval : 0.80 , 2.28 ) for stroke , and 1.07 ( 95 % confidence interval : 0.71 , 1.61 ) for CVD . For reserpine , the corresponding relative risks and confidence intervals were 0.65 ( 0.26 , 1.59 ) for death , 0.27 ( 0.04 , 2.26 ) for stroke , and 0.55 ( 0.20 , 1.49 ) for CVD . Thus , the beneficial effects in several outcomes in Systolic Hypertension in the Elderly Program ( SHEP ) were due to the treatment regimen of lowering blood pressure based on low-dose chlorthalidone ( plus atenolol or reserpine as required to meet blood pressure criteria ) . Additional ( independent ) benefits attributable to atenolol or to reserpine were not identified . However , a greater number of patients might have been necessary to adequately evaluate potential differential effects of these drugs , especially for reserpine A multi-centre study was carried out to examine the antihypertensive effect and adverse event profile of felodipine in an extended-release ( ER ) formulation given once daily as monotherapy . Doses of 5 mg , 10 mg or 20 mg felodipine ER were compared with placebo in 183 patients with mild or moderate hypertension . All antihypertensive medication was discontinued on entering a 4-week placebo run-in period . If , at the end of the run-in period , supine diastolic blood pressure was in the range greater than 95 less than 120 mmHg , patients were r and omly allocated to double-blind treatment with felodipine , 5 mg , 10 mg or 20 mg , or placebo , to be taken once daily for 4 weeks . Supine and st and ing blood pressure , heart rate and body weight were measured every 2 weeks during the trial . Assessment s were made 24 hours after intake of the study drug . Adverse events were recorded at each review . Over the 4-week treatment period , a dose-related decrease in supine diastolic blood pressure was observed , this reduction occurring already during the first 2 weeks of active treatment . In the placebo group and the felodipine 5 mg , 10 mg and 20 mg groups , supine blood pressure ( systolic/diastolic ) decreased by 7/6 mmHg , 9/8 mmHg , 12/10 mmHg and 14/11 mmHg , respectively . Supine diastolic blood pressure reduction in the felodipine 10 mg group and both systolic and diastolic blood pressure reductions in the 20 mg group were significantly greater than with placebo . St and ing diastolic blood pressure reduction was significantly greater in all three dose groups on felodipine compared with placebo . ( ABSTRACT TRUNCATED AT 250 WORDS 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 Aliskiren is a novel orally active renin inhibitor for the treatment of hypertension . This study evaluated the antihypertensive efficacy , safety and tolerability of aliskiren in Japanese patients with hypertension . Forty hundred and fifty-five Japanese men and women with a mean sitting diastolic blood pressure of 95–110 mmHg were r and omized to receive once-daily double-blind treatment for 8 weeks with aliskiren 75 , 150 or 300 mg or placebo . Aliskiren produced significant , dose-dependent reductions in mean sitting diastolic blood pressure ( p<0.0005 vs. placebo for each dose ) and mean sitting systolic blood pressure ( p<0.001 vs. placebo for each dose ) . The placebo-corrected reductions in mean sitting systolic/diastolic blood pressure were 5.7/4.0 , 5.9/4.5 and 11.2/7.5 mmHg in the aliskiren 75 , 150 and 300 mg groups , respectively . After 8 weeks ' treatment , 27.8 % , 47.8 % , 48.2 % and 63.7 % of patients in the placebo and aliskiren 75 , 150 and 300 mg groups , respectively , achieved a successful treatment response ( diastolic blood pressure < 90 mmHg and /or reduced by ≥10 mmHg from baseline ; p<0.005 vs. placebo for each dose ) . Aliskiren treatment was well tolerated , with the incidence of adverse events reported in the active treatment groups ( 53–55 % ) being similar to that in the placebo group ( 50 % ) . This study , which is the first to assess the antihypertensive efficacy and safety  of aliskiren in Japanese patients with hypertension , demonstrates that the once-daily oral renin inhibitor aliskiren provides significant , dose-dependent reductions in blood pressure with placebo-like tolerability Background : Combined regimen may be superior to monotherapy in blood pressure ( BP ) control . Since BP control is crit‐ically related to cardiovascular mortality and morbidity in hypertensive patients , this study aim ed to evaluate the efficacy and safety of a low‐dose combined regimen of preterax compared with cilazapril monotherapy for better BP control in treated hypertensive patients . Methods : Stable hypertensive patients were evaluated if their systolic BP ( SBP ) was > 130 mmHg and /or diastolic BP ( DBP ) was > 85 mmHg even with up to 2 antihypertensive drugs . Patients were excluded if they were on angiotensin‐converting enzyme inhibitors , angiotensin II receptor blockers or a diuretic . They were then r and omized to receive either preterax ( perindopril 2 mg and indapamide 0.625 mg ) or cilazapril 2.5 mg once daily in a double‐blind fashion for a period of 12 weeks after a 2‐week placebo run‐in phase . Sitting BP was recorded and the safety and efficacy were evaluated at each visit every 4 weeks . Response was defined as positive if SBP was ≤140 mmHg and DBP was ≤90 mmHg at the last visit or there was > 20 mmHg reduction in SBP and /or > 10 mmHg reduction in DBP using either treatment . Plasma biochemical analysis was performed both before and after the treatment . Results : Among the 47 patients initially enrolled , 41 completed the study ( 21 in the preterax group , 20 in the cilazapril group ) . There was no difference in the number of adverse events between the 2 groups . SBP was significantly reduced by preterax ( 13.43 ±12.48 mmHg , p < 0.0001 ) and cilazapril ( 9.00 ±13.75 mmHg , p < 0.05 ) . However , DBP was significantly reduced only by preterax ( 7.67 ±9.40 mmHg , p = 0.0009 ) but not by cilazapril ( 3.60 ±8.37 mmHg , p > 0.05 ) . The response rate was significantly higher to preterax ( 100 % ) than to cilazapril ( 70 % ) ( p = 0.0086 ) . Conclusion : Though similar in safety , combined regimen preterax was more effective than cilazapril to facilitate adequate BP control in already‐treated hypertensives . It can be added on to other antihypertensives for better BP control in clinical hypertension . [ J Chin Med Assoc 2008;71(5):247–253
A dose of reserpine 0.5 mg/day or greater achieved the SBP effects .
AUTHORS ' CONCLUSIONS Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs .
BACKGROUND Many antihypertensive agents exist today for the treatment of primary hypertension ( systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg , or both ) .
R and omised controlled trials ( RCTs ) have been carried out to investigate the evidence for these agents .
There is , for example , strong RCT evidence that thiazides reduce mortality and morbidity .
Some of those trials used reserpine as a second-line therapy .
However , the dose-related blood pressure reduction with this agent is not known .
OBJECTIVES The primary objective of this review was to quantify the dose-related efficacy of reserpine versus placebo or no treatment in reducing systolic blood pressure ( SBP ) or diastolic blood pressure ( DBP ) , or both .
We also aim ed to evaluate the dose-related effects of reserpine  on mean arterial blood pressure ( MAP ) and heart rate ( HR ) , as well as the dose-related effects on withdrawals due to adverse events .