Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. Combination of a thiazide, a vasodilator and reserpine compared with methyldopa plus hydrochlorothiazide in the treatment of hypertension in Zimbabwe. A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension. South African hypertension guideline 2011. 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 Reserpine plus hydrochlorothiazide and sotalol plus hydrochlorothiazide in Black and Indian hypertensive patients. The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group. Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) analyses performed up to 1992. Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension Study population and treatment titration in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). Blood Pressure Reduction: An Added Benefit of Sodium–Glucose Cotransporter 2 Inhibitors in Patients With Type 2 Diabetes Diltiazem for treatment of essential hypertension: a double-blind controlled study with reserpine. The Hypertension Optimal Treatment (HOT) Study: 24-month data on blood pressure and tolerability. Felodipine extended release in mild to moderate hypertension. The BBB Study: the effect of intensified antihypertensive treatment on the level of blood pressure, side-effects, morbidity and mortality in "well-treated" hypertensive patients. Behandla Blodtryck Bättre. The Hypertension Optimal Treatment (HOT) Study--patient characteristics: randomization, risk profiles, and early blood pressure results. Treatment of Hypertensive Urgencies with Oral Nifedipine, Nicardipine, and Captopril [Efficacy of monotherapy with 15 antihypertensive agents in treating essential hypertension assessed by 24-hour ambulatory blood pressure monitoring]. 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. Protocol for Past BP: a randomised controlled trial of different blood pressure targets for people with a history of stroke of transient ischaemic attack (TIA) in primary care Comparative antihypertensive effects of losartan 50 mg and losartan 50 mg titrated to 100 mg in patients with essential hypertension. Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial
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 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 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 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 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 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 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 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 Hypertension is increasingly common with advancing age and a risk factor for all kinds of cardiovascular complications . Moreover , cardiovascular disease is a major cause of morbidity and mortality in the elderly . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was set up by the Swedish Hypertension Society to investigate the value of antihypertensive treatment in the elderly . In this placebo controlled r and omised prospect i ve study 1,627 men and women aged 70 - 84 years with a supine blood pressure > or = 180/105 mmHg ( and /or ) but not isolated systolic hypertension participated . Three beta-blockers and one diuretic were used as blood pressure lowering agents and the average follow-up in the study was 25 months ( 3,390 patient-years ) . Administration of active antihypertensive therapy , reduced supine blood pressure from 195/102 mmHg to 167/87 mmHg at longest follow-up in comparison with placebo . A majority of the patients needed combined treatment to reach the goal blood pressure ( 160/95 mmHg ) . Associated with a fall in blood pressure were significant reductions in all cardiovascular primary endpoints ( -40 % , p = 0.0031 ) , in fatal and non-fatal stroke ( -47 % , p = 0.0081 ) and in total mortality ( -43 % , p = 0.0079 ) . In addition to the substantial effects on primary endpoints active treatment also showed clinical ly relevant effects on secondary endpoints ( e.g. heart failure ) . The impact on cardiovascular morbidity and mortality with antihypertensive treatment in this elderly cohort was greater than previously seen in middle-aged hypertensive patients , with maintained tolerability and a favourable cost-effectiveness ratio . Finally , women benefited from treatment at least as much as men 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 OBJECTIVES To ascertain the baseline characteristics of the high-risk hypertensive patients entering the International Nifedipine GITS Study : Intervention as a Goal in Hypertension Treatment ( INSIGHT ) . To determine the success of single and combination therapy in achieving target blood pressures in such a population . DESIGN INSIGHT is a double-blind , prospect i ve outcome trial comparing the efficacy of the calcium channel blocker , nifedipine GITS , and the thiazide , co-amilozide , in preventing myocardial infa rct ion and stroke . We recruited 2996 men and 3454 women , aged 55 - 80 years , with blood pressure during placebo run-in > 150/95 mmHg or isolated systolic blood pressure > 160 mmHg from nine countries . Treatment allocation to nifedipine GITS 30 mg daily or co-amilozide ( hydrochlorothiazide 25 mg/amiloride 5 mg ) once daily was performed by minimization rather than r and omization to balance additional risk factors . This was followed by four optional increases in treatment : dose-doubling of the primary drug , addition of atenolol 25/50 mg or enalapril 5/10 mg , and then any other hypotensive drug excluding calcium blockers or diuretics . Target blood pressure was 140/90 mmHg or a fall > or = 20/10 mmHg . RESULTS Blood pressure at r and omization was 172+/-15 / 99+/-9 mmHg . Thirteen per cent of the patients were previously untreated . The proportions of each additional risk factors were : smoking > 10/day , 29 % ; cholesterol > 6.43 mmol/l , 52 % ; family history of premature myocardial infa rct ion or stroke , 21 % ; diabetes mellitus 20 % ; left ventricular hypertrophy , 10 % ; previous myocardial infa rct ion , other presentations of coronary heart disease , and peripheral vascular disease , each 6 % ; proteinuria , 3 % . Fifty-five per cent of patients had one additional risk factor , whereas 33 % , 9 % and 3 % had two , three or more additional risk factors , respectively . The blood pressure ( and falls in blood pressure ) at the end of titration and at 1 year after minimization was 139+/-12 / 82+/-7 mmHg ( 33+/-15 / 17+/-9 ) in the 5226 patients still on r and omized treatment The numbers requiring the four treatment increments were , respectively , 1591 , 780 , 597 and 294 , meaning that almost 70 % of patients on r and omized treatment in INSIGHT are receiving only the primary drug . At one year , 69 % of patients had a blood pressure < or = 140/90 mmHg . CONCLUSION INSIGHT is one of the first double-blind comparisons of active antihypertensive treatments , requiring high-risk patients to achieve sufficient power . Despite this requirement , it is possible to achieve good blood pressure control in most patients without the addition of multiple additional treatments that may dilute any differences between the primary agents Sodium – glucose cotransporter 2 ( SGLT2 ) inhibitors are a newly approved class of glucose-lowering medications with a novel mechanism of action . These agents increase glycosuria , which leads to improved glucose control . They also produce an osmotic diuresis that , in part , contributes to blood pressure reduction and calorie loss secondary to glycosuria leading to weight loss ( 1,2 ) . A recent review of SGLT2 inhibitors focuses on the blood pressure – lowering effects of the two approved glucose-lowering agents , dapagliflozin and canagliflozin ( 3 ) . While not approved as antihypertensive agents , they may potentially aid in lowering blood pressure in patients with diabetes . A review of studies in both hypertensive and normotensive patients with type 2 diabetes demonstrates a 4–10 mmHg reduction of systolic blood pressure ( 3 ) . In this issue of Diabetes Care , Tikkanen et al. ( 4 ) investigate the effectiveness and safety of the newest agent in this class , empagliflozin , on blood pressure using 24-h ambulatory blood pressure monitoring . This study r and omized over 800 subjects with type 2 diabetes , mean age of 60 years , and good kidney function ( i.e. , a mean estimated glomerular filtration rate [ eGFR ] of 84 mL/min/1.73 m2 ) . These subjects either were normotensive ( < 140/90 mmHg ) or had stage 1 hypertension ( ≥140/90 < 160/99 mmHg ) . They were r and omized to either empagliflozin 10 mg daily , empagliflozin 25 mg In a double-blind , parallel , 12-week trial , antihypertensive effects of diltiazem and reserpine were compared in 107 patients with essential hypertension .  Diltiazem reduced blood pressure from 176/100 mmHg to 154/86 mmHg after 12 weeks , and reserpine reduced blood pressure from 171/96 mmHg to 155/85 mmHg . The difference between diltiazem and reserpine was not statistically significant . However , among a subset of patients given 180 mg/day of diltiazem , a significantly better antihypertensive effect was achieved than among a subset given 0.3 mg of reserpine . The incidence of side effects and complications in the diltiazem group was about one half that in the reserpine group ( 12.3 % and 27.1 % , respectively ) . Side effects of diltiazem were mild , and the drug was extremely well tolerated . These results show that diltiazem is an effective antihypertensive drug for the treatment of mild to moderate essential hypertension The Hypertension Optimal Treatment ( HOT ) Study is an ongoing prospect i ve r and omized , multicentre trial conducted in 26 countries . There are two main aims of the study . The first is to evaluate the relationship between three levels of target diastolic blood pressure ( < or = 90 , < or = 85 or < or = 80 mmHg ) and the incidence of cardiovascular morbidity and mortality in hypertensive patients . The second is to determine the effect on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) compared with placebo .  Altogether 18,790 patients have been recruited and r and omized , and two-year data are now available for all patients . This is a report on the blood pressures achieved , the tolerability , and other available data after 24 months of follow-up of all patients . Special emphasis is given to the subgroup of elderly patients ( > or = 65 years , n = 5988 ) compared with young patients ( < 65 years , n = 12 802 ) . On average , patients in the < or = 90 mmHg diastolic blood pressure target group have reached 85 mmHg , in the < or = 85 mmHg target group patients have reached 83 mmHg and in the < or = 80 mmHg target group patients have reached 81 mmHg . The percentage of those achieving target blood pressure in each target group at 24 months of follow-up is 85 % in the < or = 90 mmHg target group , 75 % in the < or = 85 mmHg target group and 57 % in the < or = 80 mmHg target group . In the elderly subgroup ( > or = 65 years of age ) , the percentage of patients achieving target at 24 months is higher for all target groups , namely 89 % in the < or = 90 mmHg group , 80 % in the 85 mmHg group and 62 % in the 80 mmHg group . Antihypertensive treatment was initiated with a calcium antagonist , felodipine , at a dose of 5 mg once daily . If target blood pressure was not reached , additional antihypertensive therapy , with either an angiotensin converting enzyme ( ACE ) inhibitor or a beta-adrenoceptor blocking agent , was given . Further dose adjustments were made in accordance with a set protocol . As a fifth , and final , step , a diuretic could be added . There have been relatively few side effects in this large , multinational study of hypertensive patients . Only ankle oedema and coughing exceed a frequency of 0.5 % ( ankle oedema 1.3 % in young and 1.7 % in elderly ; coughing 0.5 % in young and elderly ) . After two years , 84 % of all patients are still taking their baseline therapy , felodipine . The 24-month data presented here indicate that it should be possible to fulfil the primary aims of the HOT Study 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 The BBB study ( Swedish for Beh and la Blodtryck Bättre or Treat Blood Pressure Better ) was a multicenter trial design ed to investigate three aspects of antihypertensive treatment : i ) Is it possible to lower the diastolic blood pressure further in " well-treated " hypertensive patients through intensified therapy ? ii ) Can this aim be fulfilled without increasing the incidence or severity of side-effects ? iii ) If i ) and ii ) can be answered in the affirmative , will the further reduction in diastolic blood pressure be associated with a further reduction in hypertension-associated mortality and morbidity ? Altogether 2127 hypertensive men and women with an average age of 59.8 years ( 46 - 71 ) were recruited at 142 primary health care centers in Sweden . Approximately 10,000 patient-years were accumulated . All patients had treated essential hypertension and all had diastolic blood pressures in the range 90 - 100 mmHg on three consecutive visits before entering the study . The patients were r and omized to either intensified treatment aim ing at a blood pressure < or = 80 mmHg diastolic ( group A ) or to unchanged therapy ( group B ) . A difference between group A and group B in diastolic blood pressure of 7 - 7.5 mmHg was achieved for > 4 years . Adverse effects were studied in detail in 100 r and omly selected patients from each group using a special question naire and a visual analogue scale . The adverse effect score fell significantly in group A but remained unchanged in group B. Regarding cardiovascular morbidity and mortality there were no significant differences between groups A and B , the total number of strokes and myocardial infa rcts being 28 in group A and 29 in group B. ( ABSTRACT TRUNCATED AT 250 WORDS The Hypertension Optimal Treatment ( HOT ) Study is a prospect i ve , r and omized , multicenter trial being conducted in 26 countries . Its main aim is to evaluate the relationship between three levels of target diastolic blood pressure ( < or = 90 , < or = 85 or < or = 80 mmHg ) and cardiovascular morbidity and mortality in hypertensive patients . In addition , the study will examine the effects on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) or placebo . In the HOT Study , basic antihypertensive treatment is initiated with the calcium antagonist felodipine at a dose of 5 mg daily . If target blood pressure is not reached , additional antihypertensive therapy with either an angiotensin converting enzyme ( ACE ) inhibitor or a beta-adrenoceptor blocking agent is given . Further dosage adjustments are made in accordance with a set protocol . As a fifth and final step , a diuretic may be added . Inclusion of patients was stopped on April 30 , 1994 . At that time 19,196 patients had been r and omized . There were 9,055 ( 47 % ) women and 10,141 ( 53 % ) men with an average age of 61.5 + /- 7.5 ( SD ) years . At enrollment , 52 % of patients were receiving antihypertensive treatment . These patients entered a wash-out period of at least 2 weeks before r and omization . The average r and omization blood pressure in untreated patients was 169 + /- 14/106 + /- 3 mmHg and in the treated patients 170 + /- 14/105 + /- 3 mmHg . On August 15 , 1994 , blood pressure data were available for 14,710 and 10,275 patients , who had completed 3 and 6 months treatment , respectively . The average reduction in diastolic blood pressure was 22 mmHg after 6 months . ( ABSTRACT TRUNCATED AT 250 WORDS Sixty-five patients with unclomplicated hypertenive urgencies were treated in the emergency and cardiology departments with 20 mg nifedipine , 20 mg nicardipine , or 25 mg captopril in a r and omized study . The study population consisted of 65 patients ranging in age from forty-one to seventy-one .  Blood pressure and heart rate were assessed for six hours after intake of the antihyper tensive agents . Within sixty minutes nifedipine reduced blood pressure by an average of 74.7 mmHg for the systolic and 35.4 mmHg for the diastolic . Average heart rate increased significantly by 11.6 beats/min at within thirty minutes . Nicardipine and captopril produced equivalent falls in systolic ( -81.6 and -79.4 mmHg ) and diastolic ( -37.3 and -33 mmHg ) blood pressure respectively , but did not increase heart rate significantly . The antihypertensive effect of each drug was maintained until six hours after medication . In conclusion , nifedipine , nicardipine , and captopril show similar efficacy in the treatment of hypertensive urgencies . The authors believe that these drugs can be used as first-line therapy in the treatment of hypertensive urgencies safely and effectively OBJECTIVE To evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension . METHODS After 2-week wash-out , a total of 370 patients with seated diastolic blood pressure 95 - 114 mmHg and seated systolic blood pressure < 180 mmHg were r and omized to different therapeutic groups .  24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks . RESULT All the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin , terazosin , and torasemide . CONCLUSION The result suggested that the angiotensin-converting enzyme inhibitors , angiotensin II receptor blockers , beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension , while the low-dose doxazosin , terazosin and torasemide can be used for combination therapy but not for monotherapy 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 Background Blood pressure ( BP ) lowering in people who have had a stroke or transient ischaemic attack ( TIA ) leads to reduced risk of further stroke . However , it is not clear what the target BP should be , since intensification of therapy may lead to additional adverse effects . PAST BP will determine whether more intensive BP targets can be achieved in a primary care setting , and whether more intensive therapy is associated with adverse effects on quality of life . Methods / Design This is a r and omised controlled trial ( RCT ) in patients with a past history of stroke or TIA . Patients will be r and omised to two groups and will either have their blood pressure ( BP ) lowered intensively to a target of 130 mmHg systolic , ( or by 10 mmHg if the baseline systolic pressure is between 125 and 140 mmHg ) compared to a st and ard group where the BP will be reduced to a target of 140 mmHg systolic . Patients will be managed by their practice at 1 - 3 month intervals depending on level of BP and followed-up by the research team at six monthly intervals for 12 months.610 patients will be recruited from approximately 50 general practice s. The following exclusion criteria will be applied : systolic BP < 125 mmHg at baseline , 3 or more anti-hypertensive agents , orthostatic hypotension , diabetes mellitus with microalbuminuria or other condition requiring a lower treatment target or terminal illness . The primary outcome will be change in systolic BP over twelve months . Secondary outcomes include quality of life , adverse events and cardiovascular events . In-depth interviews with 30 patients and 20 health care practitioners will be undertaken to investigate patient and healthcare professionals underst and ing and views of BP management . Discussion The results of this trial will inform whether intensive blood pressure targets can be achieved in people who have had a stroke or TIA in primary care , and help determine whether or not further research is required before recommending such targets for this population .Trial Registration IS RCT The antihypertensive activity of losartan potassium ( losartan , Cozaar ) , an angiotensin II receptor antagonist , was evaluated in a parallel 12-week , double-blind , placebo-controlled trial in hypertensive patients with mild-to-moderate hypertension . After a 4-week , single-blind , placebo lead-in period , which included monitoring of baseline variables , 366 patients with a group mean sitting diastolic blood pressure of 101 + /- 5 ( s.d . ) mmHg were assigned r and omly to one of three treatment groups : placebo , losartan 50 mg , or losartan 50 mg with the option to titrate to 100 mg after the first 6 weeks if the target sitting diastolic blood pressure ( < 90 mmHg ) was not reached . To assess the potential blood pressure response associated with the act of titration , patients in the placebo and losartan 50 mg treatment groups with a sitting diastolic blood pressure of > or = 90 mmHg at week 6 were mock titrated ( changed to a new tablet containing the same study medication and dose ) . Sitting diastolic blood pressure was also evaluated at the end of the trial during a 1-week off-drug period to assess for rebound hypertension . At week 6 , patients in the active-drug-treatment arms experienced significantly greater peak ( 6 h post-dose ) and trough ( 24 h post-dose ) reduction in systolic and diastolic sitting blood pressures compared with placebo ( p < or = 0.01 ) . Based on trough blood pressures at week 12 , active drug ( both arms ) was more effective than placebo in lowering sitting diastolic blood pressure , with a very small additional benefit associated with increasing the dose of losartan to 100 mg in patients who did not reach the target blood pressure after the first 6 weeks on losartan 50 mg . There was no evidence of rebound hypertension during 1 week after withdrawal of losartan . The correlation between baseline plasma renin activity and reduction in peak and trough blood pressure at week 12 , although statistically significant , was generally poor in the active treatment groups . In this trial , losartan was efficacious and well tolerated , and was similar to placebo with regard to adverse-experience profile . Adverse experiences that could reasonably be related to excessive lowering of blood pressure were not common and there was no evidence of rebound hypertension Objectives This double-blind study compared long-term efficacy , safety and tolerability of the oral direct renin inhibitor aliskiren and the angiotensin-converting enzyme inhibitor ramipril alone and combined with hydrochlorothiazide in patients with hypertension . Methods After a 2–4-week placebo run-in , 842 patients [ mean sitting diastolic blood pressure ( msDBP ) 95–109 mmHg ] were r and omized to aliskiren 150 mg ( n = 420 ) or ramipril 5 mg ( n = 422 ) . Dose titration ( to aliskiren 300 mg/ramipril 10 mg ) and subsequent hydrochlorothiazide addition ( 12.5 mg , titrated to 25 mg if required ) were permitted at weeks 6 , 12 , 18 and 21 for inadequate blood pressure control . Patients completing the 26-week active-controlled treatment period were re-r and omized to their existing regimen or placebo for a 4-week double-blind withdrawal phase . Results Six hundred and eighty-seven patients ( 81.6 % ) completed the active treatment period . At week 26 , aliskiren-based therapy produced greater mean reductions in mean sitting systolic blood pressure ( 17.9 versus 15.2 mmHg , P = 0.0036 ) and msDBP ( 13.2 versus 12.0 mmHg , P = 0.025 ) , and higher rates of systolic blood pressure control ( < 140 mmHg ; 72.5 versus 64.1 % , P = 0.0075 ) compared with ramipril-based therapy . During withdrawal , blood pressure increased more rapidly after stopping ramipril than aliskiren-based therapy  ; median blood pressure reached 140/90 mmHg after 1 and 4 weeks , respectively . Blood pressure reductions were maintained with continued active treatment . Aliskiren therapy was well tolerated . Overall adverse event rates were similar with aliskiren ( 61.3 % ) and ramipril ( 60.4 % ) ; cough was more frequent with ramipril ( 9.5 % ) than aliskiren ( 4.1 % ) . Conclusions Aliskiren-based therapy was well tolerated and produced sustained blood pressure reductions in patients with hypertension over 6 months , greater than those with ramipril-based therapy
Due to significant heterogeneity across trials , a significant effect in diastolic blood pressure ( DBP ) , mean arterial pressure ( MAP ) , and heart rate ( HR ) could not be found .
The SBP effects were achieved with 0.5 mg/day or greater .
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 and /or diastolic blood pressure > /=90 mmHg ) .
R and omised controlled trials have been carried out to investigate the evidence for these agents .
There is , for example , strong RCT evidence that thiazides reduce mortality and morbidity .
Reserpine has been used as a second-line therapy in some of those trials .
However , the dose-related blood pressure reduction with this agent is not known .
OBJECTIVES To investigate the dose-related effect of reserpine on blood pressure , heart rate and withdrawals due to adverse events .