title: Apparent effect on blood pressure is only partly responsible for the risk reduction due to antihypertensive treatments. Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) Lifestyle intervention: results of the Treatment of Mild Hypertension Study (TOMHS). Long-Term Antihypertensive Efficacy and Safety of the Oral Direct Renin Inhibitor Aliskiren: A 12-Month Randomized, Double-Blind Comparator Trial With Hydrochlorothiazide Results of the pilot study for the Hypertension in the Very Elderly Trial A 12-month comparison of ACE inhibitor and CA antagonist therapy in mild to moderate essential hypertension--The GLANT Study. Study Group on Long-term Antihypertensive Therapy. Randomised trial of effects of calcium antagonists compared with diuretics and β-blockers on cardiovascular morbidity and mortality in hypertension: the Nordic Diltiazem (NORDIL) study Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Syst-Eur. A multicentre trial on the treatment of isolated systolic hypertension in the elderly: Objectives, protocol, and organization Hypotensive therapy in stroke survivors. Blood pressure reduction in elderly: a randomised controlled trial of methyldopa. Detection and treatment of hypertension in older individuals. Prevention of hypertension in patients with pre-hypertension: protocol for the PREVER-prevention trial Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39 Treatment of hypertension in patients 80 years of age or older. Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study. Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET-COG): a double-blind, placebo controlled trial The effects of blood pressure reduction in older patients: an overview of five randomized controlled trials in elderly hypertensives. Medical Research Council's Treatment Trial for mild hypertension: an interim report. Comparison of the antihypertensive efficacy and adverse reactions to two doses of bendrofluazide and hydrochlorothiazide and the effect of potassium supplementation on the hypotensive action of bendrofluazide: substudies of the Medical Research Council's trials of treatment of mild hypertension: Med Effects of a fixed combination of perindopril and indapamide on macrovascular and microvascular outcomes in patients with type 2 diabetes mellitus (the ADVANCE trial): a randomised controlled trial Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 STOP-Hypertension 2: a prospective intervention trial of "newer" versus "older" treatment alternatives in old patients with hypertension. Swedish Trial in Old Patients with Hypertension. Correlates of blood pressure change in middle-aged male mild hypertensives: results from the untreated control group in the Oslo hypertension trial. The Oslo Study. The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double-blind intervention trial Oslo Hypertension Study Isolated systolic hypertension: data from the European Working Party on High Blood Pressure in the Elderly. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. Long-term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men. Prospective study on the treatment of mild hypertension in the aged. The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. Morbidity and mortality in patients randomised to double-blind treatment with a long-acting calcium-channel blocker or diuretic in the International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment (INSIGHT) The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. Long-term safety and efficacy of moexipril alone and in combination with hydrochlorothiazide in elderly patients with hypertension. Effect of two different therapeutic approaches on total and cardiovascular mortality in a Cardiovascular Study in the Elderly (CASTEL). Randomised trial of treatment of hypertension in elderly patients in primary care. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Treatment of mild hypertension: a five year controlled drug trial. The Oslo study. Effects of treatment in hypertension. Results of a controlled study. Results of MRC (UK) trial of drug therapy for mild hypertension. Randomised, double blind, multicentre comparison of hydrochlorothiazide, atenolol, nitrendipine, and enalapril in antihypertensive treatment: results of the HANE study Systolic Hypertension in the Elderly: Long‐Term Lacidipine Treatment: Objective, Protocol, and Organization Investigating strategies to improve attendance at screening visits in a randomized trial Treatment of elderly hypertensives in Japan: National Intervention Cooperative Study in Elderly Hypertensives. The National Intervention Cooperative Study Group. Trial of Secondary Prevention With Atenolol After Transient Ischemic Attack or Nondisabling Ischemic Stroke RETRACTED: Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study Long-Term Effects of Cholesterol Lowering and Angiotensin-Converting Enzyme Inhibition on Coronary Atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study. The Hypertension Optimal Treatment (HOT) Study: 12-month data on blood pressure and tolerability. With special reference to age and gender. Serum glucose levels during long-term observation of treated and untreated men with mild hypertension. The Oslo study. Evaluation of drug treatment in mild hypertension: VA-NHLBI feasibility trial. Plan and preliminary results of a two-year feasibility trial for a multicenter intervention study to evaluate the benefits versus the disadvantages of treating mild hypertension. Prepared for the Veterans Administration-N Final outcome results of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS). A randomized controlled trial. Study population and treatment titration in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT). INSIGHT: international nifedipine GITS study intervention as a goal in hypertension treatment. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8).
abstract: The mechanism of risk reduction obtained by blood pressure-lowering pharmacological treatment remains unclear . We explored the amount of risk reduction attributable to the apparent effect of antihypertensive medicines on blood pressure by using the capture approach . Five r and omized , placebo or nil controlled trials with a total of 28,997 subjects and 1,935 cardiovascular fatal or non-fatal events from the INDANA data base met the eligibility criteria . Computations were performed on the original individual records using multiple Cox 's proportional hazard regression models design ed for meeting the assumed treatment mode of action and comparing relevant assumptions . For coronary event , the results are inconclusive essentially because the risk reduction is mild . However , for stroke the risk reduction adjusted for baseline risk factors is 34 % ( P<0.0001 ) . The part explained by the effect of treatment on systolic blood pressure is 49 % of this reduction , with 95 % confidence interval not including 100 % . This result suggests that the apparent effect on blood pressure is not the only cause of stroke risk reduction in hypertensive subjects su bmi tted to an antihypertensive medicine Although the benefits of antihypertensive treatment in " young " elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality BACKGROUND Questions regarding the efficacy of nonpharmacologic approaches for the treatment of stage 1 hypertension were addressed as part of the Treatment of Mild Hypertension Study ( TOMHS ) , a 4-year , r and omized clinical trial ( N = 902 ) . This report describes the lifestyle intervention program used in TOMHS , presents data on the lifestyle changes observed , and focuses on the effect of weight loss on blood pressure and blood lipid levels . METHODS Participants were r and omly assigned to receive either placebo or one of five different antihypertensive medications . All took part in a lifestyle intervention program to reduce weight and sodium and alcohol intake  and to increase physical activity .  RESULTS Substantial changes from baseline levels were achieved for all lifestyle intervention variables . Mean weight change was -10.5 lb ( -5.6 % ) at 1 year , -8.5 lb ( -4.5 % ) at 2 years , -7.4 lb ( -4.0 % ) at 3 years , and -5.7 lb ( -3.0 % ) at 4 years . At 4 years , 70 % of participants remained below baseline weight and 34 % maintained a weight loss of 10 lb or greater . Mean change in urinary sodium excretion was -12.5 mmol/8 hr ( -23 % ) at 1 year , -10.7 mmol/8 hr ( -20 % ) at 2 years , -8.4 mmol/8 hr ( -16 % ) at 3 years , and -4.6 mmol/8 hr ( -9 % ) at 4 years . Alcohol intake declined by 1.6 drinks/week among drinkers at 4 years . Reported leisure physical activity increased by 86 % at 1 year and remained 50 % above baseline at 4 years . Beneficial changes in blood pressure and serum lipids were associated with these changes . CONCLUSIONS These results support a role for lifestyle interventions as the initial treatment for stage 1 hypertension and demonstrate that such interventions can be successfully implemented in the clinical setting Background — Diuretics are recommended as first-line agents for the treatment of hypertension . This r and omized , double-blind , multicenter study assessed the long-term efficacy and safety of the direct renin inhibitor aliskiren in comparison with the diuretic hydrochlorothiazide in patients with essential hypertension . Methods and Results — After a 2- to 4-week placebo run-in , 1124 patients ( mean sitting diastolic blood pressure [ BP ] 95 to 109 mm Hg ) were r and omized to aliskiren 150 mg ( n=459 ) , hydrochlorothiazide 12.5 mg ( n=444 ) , or placebo ( n=221 ) once daily . Forced titration ( to aliskiren 300 mg or hydrochlorothiazide 25 mg ) occurred at week 3 ; at week 6 , patients receiving placebo were reassigned ( 1:1 ratio ) to aliskiren 300 mg or hydrochlorothiazide 25 mg . From week 12 , amlodipine 5 mg was added and titrated to 10 mg from week 18 for patients whose BP remained uncontrolled . Efficacy variables were analyzed for the intent-to-treat population with the use of the last observation carried forward method . BP reductions ( mean sitting systolic BP/mean sitting diastolic BP ) were significantly greater with aliskiren- versus hydrochlorothiazide-based treatment at week 26 ( −20.3/−14.2 versus −18.6/−13.0 mm Hg ; P<0.05 ) and were also greater at week 52 ( −22.1/−16.0 versus −21.2/−15.0 mm Hg ; P<0.05 for mean sitting diastolic BP ) . At the end of the monotherapy period ( week 12 ) , aliskiren 300 mg was superior to hydrochlorothiazide 25 mg in reducing BP ( −17.4/−12.2 versus −14.7/−10.3 mm H ; P<0.001 ) . Adverse event rates were similar with aliskiren- ( 65.2 % ) and hydrochlorothiazide-based therapy ( 61.5 % ) . Hypokalemia was more frequent with hydrochlorothiazide-based therapy than aliskiren-based therapy ( 17.9 % versus 0.9 % ; P<0.0001 ) . Conclusions — Aliskiren treatment , both as monotherapy and with optional addition of amlodipine , provided significantly greater BP reductions than the respective hydrochlorothiazide regimens . Aliskiren-based therapy was well tolerated . Direct renin inhibition with aliskiren therefore represents an effective option for the long-term treatment of essential hypertension Background The risks and benefits of treating hypertension in individuals older than 80 years are uncertain . A meta- analysis has suggested that a reduction in stroke events of 36 % may have to be balanced against a 14 % increase in total mortality . Objectives To report the results of the pilot study of the Hypertension in the Very Elderly Trial ( HYVET ) , which is in progress to address these issues . Methods The HYVET-Pilot was a multicentre international open pilot trial . In 10 European countries , 1283 patients older than 80 years and with a sustained blood pressure of 160–219/90–109 mmHg were allocated r and omly to one of three treatments : a diuretic-based regimen ( usually bendroflumethiazide ; n = 426 ) , an angiotensin-converting enzyme inhibitor regimen ( usually lisinopril ; n = 431 ) or no treatment ( n = 426 ) . The procedure permitted doses of the drug to be titrated and diltiazem slow-release to be added to active treatment . Target blood pressure was < 150/80 mmHg and mean follow-up was 13 months . Results In the combined actively treated groups , the reduction in stroke events relative hazard rate ( RHR ) was 0.47 [ 95 % confidence interval ( CI ) 0.24 to 0.93 ] and the reduction in stroke mortality RHR was 0.57 ( 95 % CI 0.25 to 1.32 ) . However , the estimate of total mortality supported the possibility of excess deaths with active treatment ( RHR 1.23 , 95 % CI 0.75 to 2.01 ) . Conclusions The preliminary results support the need for the continuing main HYVET trial . It is possible that treatment of 1000 patients for 1 year may reduce stroke events by 19 ( nine non-fatal ) , but may be associated with 20 extra non-stroke deaths Patients with mild to moderate essential hypertension were treated mainly with an ACE inhibitor ( delapril , n = 980 ) or a Ca antagonist ( n = 956 ) for 12 months , and the incidence of cerebrovascular and cardiovascular events as well as drug-related side effects were compared between the two groups . There were no significant differences between the clinical background s of the two groups . In both groups , the blood pressure was decreased significantly from 1 month of treatment onwards , with the degree of reduction being greater in the Ca antagonist group throughout the study period ( p < 0.001 ) . Cerebrovascular or cardiovascular events occurred in 11 out of 980 patients in the delapril group and 18 out of 956 patients in the Ca antagonist group ( p = NS ) . Cerebrovascular disease developed in 5 delapril-treated patients and 11 Ca antagonist-treated patients , and heart disease developed in 5 and 7 patients , respectively ( both p = NS ) . Discontinuation of treatment due to side effects was significantly more common in the delapril group than in the Ca antagonist group ( p < 0.001 ) . There was no significant difference in the incidence of cerebrovascular and cardiovascular events between the two groups , and the results suggested that blood pressure reduction per se did not necessarily lead to a parallel decrease in cerebrovascular and cardiovascular complications BACKGROUND Calcium antagonists are a first-line treatment for hypertension . The effectiveness of diltiazem , a non-dihydropyridine calcium antagonist , in reducing cardiovascular morbidity or mortality is unclear . We compared the effects of diltiazem with that of diuretics , beta-blockers , or both on cardiovascular morbidity and mortality  in hypertensive patients . METHODS In a prospect i ve , r and omised , open , blinded endpoint study , we enrolled 10,881 patients , aged 50 - 74 years , at health centres in Norway and Sweden , who had diastolic blood pressure of 100 mm Hg or more . We r and omly assigned patients diltiazem , or diuretics , beta-blockers , or both . The combined primary endpoint was fatal and non-fatal stroke , myocardial infa rct ion , and other cardiovascular death . Analysis was done by intention to treat . FINDINGS Systolic and diastolic blood pressure were lowered effectively in the diltiazem and diuretic and beta-blocker groups ( reduction 20.3/18.7 vs 23.3/18.7 mm Hg ; difference in systolic reduction p<0.001 ) . A primary endpoint occurred in 403 patients in the diltiazem group and in 400 in the diuretic and beta-blocker group ( 16.6 vs 16.2 events per 1000 patient-years ; relative risk 1.00 [ 95 % CI 0.87 - 1.15 ] , p=0.97 ) . Fatal and non-fatal stroke occurred in 159 patients in the diltiazem group and in 196 in the diuretic and beta-blocker group ( 6.4 vs 7.9 events per 1000 patient-years ; 0.80 [ 0.65 - 0.99 ] , p=0.04 ) and fatal and non-fatal myocardial infa rct ion in 183 and 157 patients ( 7.4 vs 6.3 events per 1000 patient-years ; 1.16 [ 0.94 - 1.44 ] , p=0.17 ) . INTERPRETATION Diltiazem was as effective as treatment based on diuretics , beta-blockers , or both in preventing the combined primary endpoint of all stroke , myocardial infa rct ion , and other cardiovascular death BACKGROUND It is unknown whether either the angiotensin-II-receptor blocker irbesartan or the calcium-channel blocker amlodipine slows the progression of nephropathy in patients with type 2 diabetes independently of its capacity to lower the systemic blood pressure . METHODS We r and omly assigned 1715 hypertensive patients with nephropathy due to type 2 diabetes to treatment with irbesartan ( 300 mg daily ) , amlodipine ( 10 mg daily ) , or  placebo .  The target blood pressure was 135/85 mm Hg or less in all groups . We compared the groups with regard to the time to the primary composite end point of a doubling of the base-line serum creatinine concentration , the development of end-stage renal disease , or death from any cause . We also compared them with regard to the time to a secondary , cardiovascular composite end point . RESULTS The mean duration of follow-up was 2.6 years . Treatment with irbesartan was associated with a risk of the primary composite end point that was 20 percent lower than that in the placebo group ( P=0.02 ) and 23 percent lower than that in the amlodipine group ( P=0.006 ) . The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group ( P=0.003 ) and 37 percent lower in the irbesartan group than in the amlodipine group ( P<0.001 ) . Treatment with irbesartan was associated with a relative risk of end-stage renal disease that was 23 percent lower than that in both other groups ( P=0.07 for both comparisons ) . These differences were not explained by differences in the blood pressures that were achieved . The serum creatinine concentration increased 24 percent more slowly in the irbesartan group than in the placebo group ( P=0.008 ) and 21 percent more slowly than in the amlodipine group ( P=0.02 ) . There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point . CONCLUSIONS The angiotensin-II-receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes . This protection is independent of the reduction in blood pressure it causes Summary The Syst-Eur Trial is a concerted action of the European Community ’s Medical and Health Research Programme . The trial is carried out in consultation with the World Health Organization , the International Society of Hypertension , the European Society of Hypertension and the World Hypertension League . This article describes the objectives and the protocol of Syst-Eur , a multicentre trial design ed by the European Working Party on High Blood . Pressure in the Elderly ( EWPHE ) , to test the hypothesis that antihypertensive treatment of elderly patients with isolated systolic hypertension results in a significant change in stroke morbidity and mortality . Secondary endpoints include cardiovascular events , such as myocardial infa rct ion and congestive heart failure .  To be eligible patients must be at least 60 years old and have a systolic blood pressure averaging 160–219 mmHg with a diastolic pressure less than 95 mmHg . Patients must give their informed consent and be free of major cardiovascular and non-cardiovascular diseases at entry . The patients are r and omized to active treatment or placebo . Active treatment consists of nitrendipine ( 10–40 mg/day ) , combined with enalapril ( 5–20 mg/day ) and hydrochlorothiazide ( 12.5–25 mg/day ) , as necessary . The patients of the control group receive matching placebos . The drugs ( or matching placebos ) are stepwise titrated and combined in order to reduce systolic blood pressure by 20 mmHg at least to a level below 150 mmHg . Morbidity and mortality are monitored to enable an intention-to-treat and per protocol comparison of the outcome in the 2 treatment groups . A one-year pilot trial ( 1989 ) showed that the protocol is practicable . The Ethics Committee therefore decided to start the definite study ( 1990 ) , in which r and omized patients will be followed for 5 years . Recruitment of new centres and of the required 3,000 patients will last 3 years ( until 1993 ) Abstract A prospect i ve r and omised controlled trial of hypotensive therapy in 97 hypertensive patients surviving an ischaemic-type stroke was started in 1964 and terminated 4 years later . The patients were under 80 years of age , consecutively admitted to one hospital and the control and treated groups compared well for age , sex , and severity of hypertension . The drugs used were methyldopa , bethanidine or debrisoquine combined with restriction of salt intake , weight reduction , and thiazide diuretics , and the results were analysed with regard to survival and recurrence rates . Hypertension was defined as diastolic if this pressure was 110 mm . Hg or above , and as systolic if this pressure was over 160 mm . Hg with the diastolic below 110 mm . Hg . The mortality-rate at the end of a 2 to 5 year followup was 26 % in the treated group and 46 % in the untreated , and the non-fatal recurrence-rate 14 % in the treated and 23 % in the controls . Good smooth control was essential to success , untreated patients doing better than those whose control was unsatisfactory . In patients aged over 65 treatment of systolic hypertension was of no benefit , although the diastolic hypertensives improved marginally with treatment . As age increased this effect was progressively less apparent but the figures are probably too small to mean anything . In this series significant improvement occurred in treated hypertensive patients who had survived a stroke if they were aged 65 or below , but not if they were older A total of 123 out of 549 elderly residents of local authority welfare homes in Nottinghamshire were found at screening to have a st and ing or lying diastolic blood pressure of 100 mm Hg or more . These 123 subjects were r and omly allocated to simple observation or to treatment with methyldopa . The cumulative mortality was similar in the observed and treated groups and in the normotensive group from which the subjects had been separated . Thus moderate hypertension , whether treated or not , was not a major risk predictor in the elderly population studied The Hypertension Detection and Follow-up Program screened 34,012 individuals aged 60 - 69 years old in their homes in 14 communities around the United States during 1972 and 1973 . The prevalence of hypertension , defined as diastolic blood pressure greater than or equal to 90 mmHg or on antihypertensive medication , was 42.1 % . After a second clinic screen , 2,376 hypertensives were identified and r and omized into Stepped Care , a special intensive treatment group , or Referred Care , a group referred to their usual medical care sources . These individuals were followed for five years ( until they reached the ages of 65 - 74 years ) . Over the five years , 79.4 % of older individuals remained under active care and 81.4 % of those were at their goal diastolic blood pressure . Side-effects tended to be less frequent in older individuals than in younger ones . Older Stepped Care participants with mild hypertension ( diastolic blood pressure 90 - 104 mmHg ) had a 17.2 % reduction in all-cause mortality over five years compared to Referred Care , which was primarily due to a reduction in deaths attributed to cardiovascular causes . Thus , antihypertensive treatment can be safely and beneficially administered to individuals in this age range with diastolic hypertension , including those with mild hypertension Background Blood pressure ( BP ) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension , which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age . Non-drug interventions to prevent hypertension have had low effectiveness . In individuals with previous cardiovascular disease or diabetes , the use of BP-lowering agents reduces the incidence of major cardiovascular events . In the absence of higher baseline risk , the use of BP agents reduces the incidence of hypertension . The PREVER-prevention trial aims to investigate the efficacy , safety and feasibility of a population -based intervention to prevent the incidence of hypertension and the development of target-organ damage . Methods This is a r and omized , double-blind , placebo-controlled clinical trial , with participants aged 30 to 70 years , with pre-hypertension . The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo . The primary outcomes will be the incidence of hypertension , adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG . The secondary outcomes will be fatal or non-fatal cardiovascular events : myocardial infa rct ion , stroke , heart failure , evidence of new sub- clinical atherosclerosis , and sudden death . The study will last 18 months . The sample size was calculated on the basis of an incidence of hypertension of 14 % in the control group , a size effect of 40 % , power of 85 % and P alpha of 5 % , result ing in 625 participants per group . The project was approved by the Ethics committee of each participating institution . Discussion The early use of blood pressure-lowering drugs , particularly diuretics , which act on the main mechanism of blood pressure rising with age , may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension . If this intervention shows to be effective and safe in a population -based perspective , it could be the basis for an innovative public health program to prevent hypertension in Brazil . Trial Registration Clinical Trials NCT00970931 Abstract Objective : To determine whether tight control of blood pressure with either a β blocker or an angiotensin converting enzyme inhibitor has a specific advantage or disadvantage in preventing the macrovascular and microvascular complications of type 2 diabetes . Design : R and omised controlled trial comparing an angiotensin converting enzyme inhibitor ( captopril ) with a β blocker ( atenolol ) in patients with type 2 diabetes aim ing at a blood pressure of < 150/<85 mm Hg . Setting : 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 years , mean blood pressure 160/94 mm Hg ) . Of the 758 patients allocated to tight control of blood pressure , 400 were allocated to captopril and 358 to atenolol . 390 patients were allocated to less tight control of blood pressure . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , death related to diabetes , and all cause mortality . Surrogate measures of microvascular and macrovascular disease included urinary albumin excretion and retinopathy assessed by retinal photography . Results : Captopril and atenolol were equally effective in reducing blood pressure to a mean of 144/83 mm Hg and 143/81 mm Hg respectively , with a similar proportion of patients ( 27 % and 31 % ) requiring three or more antihypertensive treatments . More patients in the captopril group than the atenolol group took the allocated treatment : at their last clinic visit , 78 % of those allocated captopril and 65 % of those allocated atenolol were taking the drug ( P<0.0001 ) . Captopril and atenolol were equally effective in reducing the risk of macrovascular end points . Similar proportions of patients in the two groups showed deterioration in retinopathy by two grade s after nine years ( 31 % in the captopril group and 37 % in the atenolol group ) and developed clinical grade albuminuria ≥300 mg/l ( 5 % and 9 % ) . The proportion of patients with hypoglycaemic attacks was not different between groups , but mean weight gain in the atenolol group was greater ( 3.4 kg v 1.6 kg ) . Conclusion : Blood pressure lowering with captopril or atenolol was similarly effective in reducing the incidence of diabetic complications . This study provided no evidence that either drug has any specific beneficial or deleterious effect , suggesting that blood pressure reduction in itself may be more important than the treatment used BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo .  The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P<0.001 ) . Fewer serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . ) The pilot study of the Systolic Hypertension in the Elderly Program was a r and omized , double-blind , placebo-controlled trial of drug therapy for isolated systolic hypertension . It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months . Mean age of the participants was 72 years ; 63 % were women , and 82 % were white . Pretreatment blood pressures averaged 172/75 mm Hg . Participants were r and omly assigned to treatment with chlorthalidone or placebo as Step I medication . Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups , respectively , with 60 % and 33 % of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit . All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk , and rates for definite " first stroke " were 8.3 and 12.8 per 1,000 years of risk . Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates . A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates BACKGROUND Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia ; however , the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting , and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence . The Hypertension in the Very Elderly trial ( HYVET ) was design ed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function . METHODS Patients with hypertension ( systolic pressure 160 - 200 mm Hg ; diastolic pressure < 110 mm Hg ) who were aged 80 years or older were enrolled in this double-blind , placebo-controlled trial . Participants were r and omly assigned to receive 1.5 mg slow release indapamide , with the option of 2 - 4 mg perindopril , or placebo . The target systolic blood pressure was 150 mm Hg ; the target diastolic blood pressure was 80 mm Hg . Participants had no clinical diagnosis of dementia at baseline , and cognitive function was assessed at baseline and annually with the mini-mental state examination ( MMSE ) . Possible cases of incident dementia ( a fall in the MMSE score to < 24 points or a drop of three points in 1 year ) were assessed by st and ard diagnostic criteria and expert review . The trial was stopped in 2007 at the second interim analysis after treatment result ed in a reduction in stroke and total mortality . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00122811 . FINDINGS 3336 HYVET participants had at least one follow-up assessment ( mean 2.2 years ) and were included : 1687 participants were r and omly assigned to the treatment group and 1649 to the placebo group . Only five reports of adverse effects were attributed to the medication : three in the placebo group and two in the treatment group . The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg , p<0.0001 ; and diastolic -5.9 mm Hg , p<0.0001 . There were 263 incident cases of dementia . The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group . There was no significant difference between treatment and placebo groups ( hazard ratio [ HR ] 0.86 , 95 % CI 0.67 - 1.09 ) ; however , when these data were combined in a meta- analysis with other placebo-controlled trials of antihypertensive treatment , the combined risk ratio favoured treatment ( HR 0.87 , 0.76 - 1.00 , p=0.045 ) . INTERPRETATION Antihypertensive treatment  in elderly patients does not statistically reduce incidence of dementia . This negative finding might have been due to the short follow-up , owing to the early termination of the trial , or the modest effect of treatment . Nevertheless , the HYVET findings , when included in a meta- analysis , might support antihypertensive treatment to reduce incident dementia Direct evidence about the effects of antihypertensive treatment on vascular disease in older patients is available from five r and omized trials conducted exclusively in patients over the age of 60 years . These trials involved a total of 12,483 individuals with systolic or diastolic hypertension ( mean age = 72 years , mean entry blood pressure = 181/88 mmHg ) . Over an average follow-up period of 4.7 years , a 15/6 mmHg difference in blood pressure between study and control groups was achieved . Among those patients assigned active treatment , stroke incidence was reduced by 34 % SD6 and coronary heart disease incidence was reduced by 19 % SD7 . These proportional reductions were of similar size to those observed in trials in predominantly younger patients . However , the absolute benefits observed in older patients were more than twice as great as those observed in younger patients . The results suggest that over 10 years , treatment would prevent at least one major vascular event among every 10 elderly patients at similar risk to those enrolled in the trials The pilot phase of the British multicentre r and omized controlled trial of treatment for mild hypertension has shown : ( 1 ) that unselected subjects , aged 35 - 64 years , with mild hypertension are willing to enter and remain in a long-term trial even though asymptomatic ; ( 2 ) that the differences of mean systolic and mean diastolic pressure achieved between treated and control subjects is sufficient to produce the expected difference in terminating events with the 18000 patients calculated as needed for the full-scale trial ; ( 3 ) that side effects with the two selected active primary regimens ( bendrofluazide and propranolol ) are common but mild ( no serious side effects or toxic reactions have been reported ) ; ( 4 ) that the work load imposed by the trial , though considerable during screening and the initiation of patients into the trial , can largely be taken by specially trained nursing staff , and when screening is completed the trial does not impose a heavy burden of follow-up examinations ; ( 5 ) that there are no adverse psychological effects caused by alerting asymptomatic people to their raised pressure and enrolling them into a prolonged programme of clinical attendance ; ( 6 ) that the total costs of carrying out a full-scale trial -- estimated at about lb.2 m ( $ U.S. 4m)--are commensurate with the potential annual savings in health service expenditure whether the trial shows treatment to be effective or unwarranted As sub studies of the Medical Research Council 's trials of treatment of mild hypertension and of hypertension in the elderly , two studies were carried out comparing the effects of different doses of two diuretics on blood pressure , concentrations of some biochemical variables , and the incidence of subjective adverse reactions . In one study , in which 484 patients with mild hypertension participated , daily doses of bendrofluazide 5 mg and 10 mg , with and without oral potassium supplements , were compared . In the second , involving 701 elderly patients with hypertension , daily doses of hydrochlorothiazide 25 mg together with amiloride 2.5 mg were compared with hydrochlorothiazide 50 mg together with amiloride 5 mg . The mean ( + /- SD ) duration s of treatment were 35 + /- 17 months in the first study and 10 + /- 7 months in the second . Neither study showed any significant difference in blood pressure response to the two doses of diuretic , whereas biochemical changes and the reported incidence of subjective adverse reactions were dose-related . In the first study , potassium supplementation with potassium chloride 16.8 or 33.6 mmol did not have a significant effect on the fall in serum potassium level , which was only slightly reduced , and did not have any significant effect on the antihypertensive effect of either dose of bendrofluazide BACKGROUND Blood pressure is an important determinant of the risks of macrovascular and microvascular complications of type 2 diabetes , and guidelines recommend intensive lowering of blood pressure for diabetic patients with hypertension . We assessed the effects of the routine administration of an angiotensin converting enzyme ( ACE ) inhibitor-diuretic combination on serious vascular events in patients with diabetes , irrespective of initial blood pressure levels or the use of other blood pressure lowering drugs . METHODS The trial was done by 215 collaborating centres in 20 countries . After a 6-week active run-in period , 11 140 patients with type 2 diabetes were r and omised to treatment with a fixed combination of perindopril and indapamide or matching placebo , in addition to current therapy . The primary endpoints were composites of major macrovascular and microvascular events , defined as death from cardiovascular disease , non-fatal stroke or non-fatal myocardial infa rct ion , and new or worsening renal or diabetic eye disease , and analysis was by intention-to-treat . The macrovascular and microvascular composites were analysed jointly and separately . This trial is registered with Clinical Trials.gov , number NCT00145925 . FINDINGS After a mean of 4.3 years of follow-up , 73 % of those assigned active treatment and 74 % of those assigned control remained on r and omised treatment . Compared with patients assigned placebo , those assigned active therapy had a mean reduction in systolic blood pressure of 5.6 mm Hg and diastolic blood pressure of 2.2 mm Hg . The relative risk of a major macrovascular or microvascular event was reduced by 9 % ( 861 [ 15.5 % ] active vs 938 [ 16.8 % ] placebo ; hazard ratio 0.91 , 95 % CI 0.83 - 1.00 , p=0.04 ) . The separate reductions in macrovascular and microvascular events were similar but were not independently significant ( macrovascular 0.92 ; 0.81 - 1.04 , p=0.16 ; microvascular 0.91 ; 0.80 - 1.04 , p=0.16 ) . The relative risk of death from cardiovascular disease was reduced by 18 % ( 211 [ 3.8 % ] active vs 257 [ 4.6 % ] placebo ; 0.82 , 0.68 - 0.98 , p=0.03 ) and death from any cause was reduced by 14 % ( 408 [ 7.3 % ] active vs 471 [ 8.5 % ] placebo ; 0.86 , 0.75 - 0.98 , p=0.03 ) . There was no evidence that the effects of the study treatment differed by initial blood pressure level or concomitant use of other treatments at baseline . INTERPRETATION Routine administration of a fixed combination of perindopril and indapamide to patients with type 2 diabetes was well tolerated and reduced the risks of major vascular events , including death . Although the confidence limits were wide , the results suggest that over 5 years , one death due to any cause would be averted among every 79 patients assigned active therapy Abstract Objective : To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes . Design : R and omised controlled trial comparing tight control of blood pressure aim ing at a blood pressure of < 150/85 mm Hg ( with the use of an angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment ) with less tight control aim ing at a blood pressure of < 180/105 mm Hg . Setting : 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 , mean blood pressure at entry 160/94 mm Hg ) ; 758 patients were allocated to tight control of blood pressure  and 390 patients to less tight control  with a median follow up of 8.4 years . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , deaths related to diabetes , and all cause mortality . Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography . Results : Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control ( 144/82 mm Hg ) compared with the group assigned to less tight control ( 154/87 mm Hg ) ( P<0.0001 ) . Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24 % in diabetes related end points ( 95 % confidence interval 8 % to 38 % ) ( P=0.0046 ) , 32 % in deaths related to diabetes ( 6 % to 51 % ) ( P=0.019 ) , 44 % in strokes ( 11 % to 65 % ) ( P=0.013 ) , and 37 % in microvascular end points ( 11 % to 56 % ) ( P=0.0092 ) , predominantly owing to a reduced risk of retinal photocoagulation . There was a non-significant reduction in all cause mortality . After nine years of follow up the group assigned to tight blood pressure control also had a 34 % reduction in risk in the proportion of patients with deterioration of retinopathy by two steps ( 99 % confidence interval 11 % to 50 % ) ( P=0.0004 ) and a 47 % reduced risk ( 7 % to 70 % ) ( P=0.004 ) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study ( ETDRS ) chart . After nine years of follow up 29 % of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures . Conclusion : Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinical ly important reduction in the risk of deaths related to diabetes , complications related to diabetes , progression of diabetic retinopathy , and deterioration in visual acuity It is well established that hypertensive patients benefit from drug treatment of their disorder . In recent years three major out-come studies of antihypertensive treatment in elderly hypertensives have shown substantial benefits , i.e. a reduction in the risk of stroke and other cardiovascular mortality and morbidity . In all these studies beta-blockers and /or diuretics were used in comparison with placebo . Newer therapeutic alternatives have , however , at least theoretically , many advantages which could result in further improvements in prognosis . The initial Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension 1 ) was conducted in men and women aged 70 - 84 years . STOP-Hypertension 2 will evaluate the therapy used in STOP-Hypertension 1 against therapy based on either ACE-inhibitors ( enalapril and lisinopril ) or on calcium antagonists ( isradipine and felodipine ) , using the PROBE design ( Prospect i ve , R and omised , Open , Blinded Endpoint evaluation ) . The primary aim will be to assess the effect on cardiovascular mortality . Statistical calculations indicate that 6,600 patients , followed for four years will be needed ( 2p < 0.05 , power 90 % ) to obtain significance if there is a 25 % difference between the new and the established therapy . Patients in primary health care ( 300 centres ) will be included if their supine blood pressure is > or = 180/105 mmHg ( and /or ) . Recruitment of patients started in September 1992 and so far more than 100 patients /week have been included The  never-treated control group  in the Oslo Study hypertension trial of middle-aged men 40 - 49 years old at entry ( n = 379 ) was studied with respect to five-year change in blood pressure and its correlates . The study began in 1972 and ended in 1979 , and each patient was followed for five years . Both baseline and rate of change of correlates were analyzed as independent variables versus rate of change in blood pressure as the dependent variable . Rate of change in serum triglycerides were found to be the strongest correlate of rate of change in blood pressure in this population of healthy mild hypertensives . In addition , rate of change in serum cholesterol and body weight made significant contributions in some analyses , but to a lower degree than did rate of change in triglycerides . The model predicts a substantial decrease in blood pressure if lipids and body weight are reduced . Rate of change in sodium , uric acid , and chloride concentrations were also associated with blood pressure change , but total degree of explanation of all explaining variables only accounted for 11 - 15 % of total variation in annual blood pressure change Background The prognostic benefits of blood pressure lowering treatment in elderly hypertensive patients were established more than a decade ago , but are less clear in those with mildly to moderately elevated blood pressure . Objective To assess whether c and esartan-based antihypertensive treatment in elderly patients with mildly to moderately elevated blood pressure confers a reduction in cardiovascular events , cognitive decline and dementia . Design Prospect i ve , double-blind , r and omized , parallel-group study conducted in 1997–2002 . Setting and participants The study was of 4964 patients aged 70–89 years , with systolic blood pressure 160–179 mmHg , and /or diastolic blood pressure 90–99 mmHg , and a Mini Mental State Examination ( MMSE ) test score ⩾ 24 . A total of 527 centres in 15 countries participated in the study . Intervention Patients were assigned r and omly to receive the angiotensin receptor blocker c and esartan or placebo , with open-label active antihypertensive therapy added as needed . As a consequence , active antihypertensive therapy was extensively used in the control group ( 84 % of patients ) . Mean follow-up was 3.7 years . Main outcome measures The primary outcome measure was major cardiovascular events , a composite of cardiovascular death , non-fatal stroke and non-fatal myocardial infa rct ion . Secondary outcome measures included cardiovascular death , non-fatal and fatal stroke and myocardial infa rct ion , cognitive function measured by the MMSE and dementia . Results Blood pressure fell by 21.7/10.8 mmHg in the c and esartan group and by 18.5/9.2 mmHg in the control group . A first major cardiovascular event occurred in 242 c and esartan patients and in 268 control patients ; risk reduction with c and esartan was 10.9 % [ 95 % confidence interval ( CI ) , −6.0 to 25.1 , P = 0.19 ] . C and esartan-based treatment reduced non-fatal stroke by 27.8 % ( 95 % CI , 1.3 to 47.2 , P = 0.04 ) , and all stroke by 23.6 % ( 95 % CI , −0.7 to 42.1 , P = 0.056 ) . There were no significant differences in myocardial infa rct ion and cardiovascular mortality . Mean MMSE score fell from 28.5 to 28.0 in the c and esartan group and from 28.5 to 27.9 in the control group ( P = 0.20 ) . The proportions of patients who had a significant cognitive decline or developed dementia were not different in the two treatment groups . Conclusions In elderly hypertensive patients , a slightly more effective blood pressure reduction during c and esartan-based therapy , compared with control therapy , was associated with a modest , statistically non-significant , reduction in major cardiovascular events and with a marked reduction in non-fatal stroke . Cognitive function was well maintained in both treatment groups in the presence of substantial blood pressure reductions . Both treatment regimens were generally well tolerated Summary The Oslo Hypertension Study started in 1972 and lasted for 66 ( range 60–78 ) months . A total of 785 healthy men , aged 40 to 49 years , with mild hypertension were r and omised to a drug-treated group and to an untreated , control group . The drugs used for treatment were hydrochlorothiazide alone in 36 % , hydrochlorothiazide and propranolol in 26 % , hydrochlorothiazide and methyldopa in 20 % , and other drugs in 18%.A total of 95 % in the drug-treated group received hydrochlorothiazide . Pressure complications , such as stroke and aneurysms , only occurred in the control group . Coronary events were more numerous in the drug-treated group , so that the total incidence of cardiovascular complications did not significantly differ between the treated and untreated groups . After 5 and 10 years , total mortality was found to be the same in both groups . However , the 10-year coronary heart disease mortality was significantly higher in the drug-treated group than in the untreated controls ( 14 vs 3 , p < 0.01 ) . Possible reasons for the failing effect of drug treatment of hypertension on coronary heart disease is discussed , and attention is drawn to the adverse effect of diuretics and β-adrenergic blockers , both on lipid and carbohydrate metabolism . This is in contrast to the α-adrenergic blocker , prazosin , which has been shown to improve the blood lipid profile The European Working Party on High Blood Pressure in the Elderly study ( EWPHE ) was a placebo-controlled , double-blind , inter-patient assessment of diuretic treatment in hypertensive patients aged 60 years or more . Of the 840 patients included in the study 247 had isolated systolic hypertension ( systolic blood pressure greater than or equal to 160 and diastolic blood pressure less than or equal to 95 mmHg ) . In those ( n = 120 ) r and omized to active treatment ( diazide-hydrochlorothiazide with triamterene + /- methyldopa )  blood pressure after 3 years was , on average , 19/8 mmHg lower than in the placebo group ( n = 119 ) and after 5 years the difference was 9/7 mmHg . Data on mortality and morbidity were insufficient for firm conclusions to be drawn . The data are presented here only to communicate the trends observed and to provide information that may be useful in the design of future trials . The trends observed for cardiac mortality , terminating non-fatal events ( including severe heart failure ) and combined fatal and non-fatal cardiovascular events follow a similar pattern to that observed in the trial overall , in that active treatment appeared to confer benefit . However , in the case of isolated systolic hypertension none of these differences between active and placebo treatment achieved statistical significance . We conclude that , given the epidemiological data incriminating systolic hypertension as a risk factor and the data presented here , a rigorous assessment of the value of treating isolated systolic hypertension is justified BACKGROUND Angiotensin-converting-enzyme inhibitors improve the outcome among patients with left ventricular dysfunction , whether or not they have heart failure . We assessed the role of an angiotensin-converting-enzyme inhibitor , ramipril , in patients who were at high risk for cardiovascular events but who did not have left ventricular dysfunction or heart failure . METHODS A total of 9297 high-risk patients ( 55 years of age or older ) who had evidence of vascular disease or diabetes plus one other cardiovascular risk factor and who were not known to have a low ejection fraction or heart failure were r and omly assigned to receive ramipril ( 10 mg once per day orally ) or matching placebo for a mean of five years . The primary outcome was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . The trial was a two-by-two factorial study evaluating both ramipril and vitamin E. The effects of vitamin E are reported in a companion paper . RESULTS A total of 651 patients who were assigned to receive  ramipril ( 14.0 percent ) reached the primary end point , as compared with 826 patients who were assigned to receive placebo ( 17.8 percent ) ( relative risk , 0.78 ; 95 percent confidence interval , 0.70 to 0.86 ; P<0.001 ) . Treatment with ramipril reduced the rates of death from cardiovascular causes ( 6.1 percent , as compared with 8.1 percent in the placebo group ; relative risk , 0.74 ; P<0.001 ) , myocardial infa rct ion ( 9.9 percent vs. 12.3 percent ; relative risk , 0.80 ; P<0.001 ) , stroke ( 3.4 percent vs. 4.9 percent ; relative risk , 0.68 ; P<0.001 ) , death from any cause ( 10.4 percent vs. 12.2 percent ; relative risk , 0.84 ; P=0.005 ) , revascularization procedures ( 16.3 percent vs. 18.8 percent ; relative risk , 0.85 ; P<0.001 ) , cardiac arrest ( 0.8 percent vs. 1.3 percent ; relative risk , 0.62 ; P=0.02 ) , [ corrected ] heart failure ( 9.1 percent vs. 11.6 percent ; relative risk , 0.77 ; P<0.001 ) , and complications related to diabetes ( 6.4 percent vs. 7.6 percent ; relative risk , 0.84 ; P=0.03 ) . CONCLUSIONS Ramipril significantly reduces the rates of death , myocardial infa rct ion , and stroke in a broad range of high-risk patients who are not known to have a low ejection fraction or heart failure OBJECTIVE To investigate the long-term effects of multifactorial primary prevention of cardiovascular diseases ( CVD ) . DESIGN The 5-year r and omized , controlled trial was performed between 1974 and 1980 . The subjects and their risk factors were reevaluated in 1985 . Posttrial mortality follow-up was continued up to December 31 , 1989 . SETTING Institute of Occupational Health , Helsinki , Finl and , and Second Department of Medicine , University of Helsinki . PARTICIPANTS In all , 3490 business executives born during 1919 through 1934 participated in health checkups in the late 1960s . In 1974 , 1222 of these men who were clinical ly healthy , but with CVD risk factors , were entered into the primary prevention trial ; 612 were r and omized to an intervention and 610 to a control group . INTERVENTIONS During the 5-year trial , the subjects of the intervention group visited the investigators every fourth month . They were treated with intensive dietetic-hygienic measures and frequently with hypolipidemic ( mainly clofibrate and /or probucol ) and antihypertensive ( mainly beta-blockers and /or diuretics ) drugs . The control group was not treated by the investigators . MAIN OUTCOME MEASURES Total mortality , cardiac mortality , mortality due to other causes . RESULTS Total coronary heart disease risk was reduced by 46 % in the intervention group as compared with the control group at end-trial . During 5 posttrial years , the risk factor and medication differences were largely leveled off between the groups . Between 1974 and 1989 the total number of deaths was 67 in the intervention group and 46 in the control group ( relative risk [ RR ] , 1.45 ; 95 % confidence interval [ CI ] , 1.01 to 2.08 ; P = .048 ) ; there were 34 and 14 cardiac deaths ( RR , 2.42 ; 95 % CI , 1.31 to 4.46 ; P = .001 ) , two and four deaths due to other CVD ( not significant ) , 13 and 21 deaths due to cancer ( RR , 0.62 ; 95 % CI , 0.31 to 1.22 ; P = .15 ) , and 13 and one deaths due to violence ( RR , 13.0 ; 95 % CI , 1.70 to 98.7 ; P = .002 ) , respectively . Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality . CONCLUSION These unexpected results may not question multifactorial prevention as such but do support the need for research on the selection and interaction(s ) of methods used in the primary prevention of cardiovascular diseases The 4 year prospect i ve trial on the effectiveness of the antihypertensive treatment was performed in 100 mild hypertensive patients of the aged , the average age being 76.1 years . Dropouts during the drug-off control period were 9 cases . The matched pair group was selected by the age , sex , and blood pressure . Forty-four drug treated cases and 47 placebo treated cases were comparable in blood pressure as well as in laboratory data . Cerebrovascular and cardiac complications were observed in 4 cases or 10.5 % in the drug group , and in 9 cases or 22.0 % in the placebo group . When 8 cases of blood pressure elevation over 200/110 mmHg in the placebo group were added to the cardiovascular complications , dropouts in placebo group reached 41.5 % , and this showed the significant difference . Other complications were observed in 12 cases or 31.6 % in the drug group and in 17 cases or 41.5 % in the placebo group . Major complications were cancers , infections , and bone or joint diseases . Blood pressure was decreased from 171/87 to 151/80 in the drug group , and the average decrease was 20/7 mmHg in 4 year period . No significant changes in hematocrit , serum protein , urea nitrogen , uric acid , sodium , and potassium were observed during the trial period . The present study suggested that antihypertensive treatment was effective in the aged with mild hypertension , and that careful follow up was needed not only for cardiovascular complications but also for general health condition Angiotensin-converting enzyme inhibitors improve endothelial function , inhibit experimental atherogenesis , and decrease ischemic events . The Quinapril Ischemic Event Trial was design ed to test the hypothesis that quinapril 20 mg/day would reduce ischemic events ( the occurrence of cardiac death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary artery bypass grafting , coronary angioplasty , or hospitalization for angina pectoris ) and the angiographic progression of coronary artery disease in patients without systolic left ventricular dysfunction . A total of 1,750 patients were r and omized to quinapril 20 mg/day or placebo  and followed a mean of 27 + /- 0.3 months . The 38 % incidence of ischemic events was similar for both groups ( RR 1.04 ; 95 % confidence interval 0.89 to 1.22 ; p = 0.6 ) . There was also no significant difference in the incidence of patients having angiographic progression of coronary disease ( p = 0.71 ) . The rate of development of new coronary lesions was also similar in both groups ( p = 0.35 ) . However , there was a difference in the incidence of angioplasty for new ( previously unintervened ) vessels ( p = 0.018 ) . Quinapril was well tolerated in patients after angioplasty with normal left ventricular function . Quinapril 20 mg did not significantly affect the overall frequency of clinical outcomes or the progression of coronary atherosclerosis . However , the absence of the demonstrable effect of quinapril may be due to several limitations in study design BACKGROUND The efficacy of antihypertensive drugs newer than diuretics and beta-blockers has not been established . We compared the effects of the calcium-channel blocker nifedipine once daily with the diuretic combination co-amilozide on cardiovascular mortality and morbidity in high-risk patients with hypertension . METHODS We did a prospect i ve , r and omised , double-blind trial in Europe and Israel in 6321 patients aged 55 - 80 years with hypertension ( blood pressure > or = 150/95 mm Hg , or > or = 160 mm Hg systolic ) . Patients had at least one additional cardiovascular risk factor . We r and omly assigned patients nifedipine 30 mg in a long-acting gastrointestinal-transport-system ( GITS ) formulation ( n=3157 ) , or co-amilozide ( hydrochlorothiazide 25 mg [ corrected ] plus amiloride 2.5 mg ; n=3164 ) . Dose titration was by dose doubling , and addition of atenolol 25 - 50 mg or enalapril 5 - 10 mg . The primary outcome was cardiovascular death , myocardial infa rct ion , heart failure , or stroke . Analysis was done by intention to treat . FINDINGS Primary outcomes occurred in 200 ( 6.3 % ) patients in the nifedipine group and in 182 ( 5.8 % ) in the co-amilozide group ( 18.2 vs 16.5 events per 1000 patient-years ; relative risk 1.10 [ 95 % CI 0.91 - 1.34 ] , p=0.35 ) . Overall mean blood pressure fell from 173/99 mm Hg ( SD 14/8 ) to 138/82 mm Hg ( 12/7 ) . There was an 8 % excess of withdrawals from the nifedipine group because of peripheral oedema ( 725 vs 518 , p<0.0001 ) , but serious adverse events were more frequent in the co-amilozide group ( 880 vs 796 , p=0.02 ) . Deaths were mainly non-vascular ( nifedipine 176 vs co-amilozide 172 ; p=0.81 ) . 80 % of the primary events occurred in patients receiving r and omised treatment ( 157 nifedipine , 147 co-amilozide , difference 0.33 % [ -0.7 to 1.4 ] ) . INTERPRETATION Nifedipine once daily and co-amilozide were equally effective in preventing overall cardiovascular or cerebrovascular complications . The choice of drug can be decided by tolerability and blood-pressure response rather than long-term safety or efficacy BACKGROUND Microalbuminuria and hypertension are risk factors for diabetic nephropathy . Blockade of the renin-angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes , but similar data are lacking for hypertensive patients with type 2 diabetes . We evaluated the renoprotective effect of the angiotensin-II-receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria . METHODS A total of 590 hypertensive patients with type 2 diabetes and microalbuminuria were enrolled in this multinational , r and omized , double-blind , placebo-controlled study of irbesartan , at a dose of either 150 mg daily or 300 mg daily , and were followed for two years . The primary outcome was the time to the onset of diabetic nephropathy , defined by persistent albuminuria in overnight specimens , with a urinary albumin excretion rate that was greater than 200 microg per minute and at least 30 percent higher than the base-line level . RESULTS The base-line characteristics in the three groups were similar . Ten of the 194 patients in the 300-mg group ( 5.2 percent ) and 19 of the 195 patients in the 150-mg group ( 9.7 percent ) reached the primary end point , as compared with 30 of the 201 patients in the placebo group ( 14.9 percent ) ( hazard ratios , 0.30 [ 95 percent confidence interval , 0.14 to 0.61 ; P < 0.001 ] and 0.61 [ 95 percent confidence interval , 0.34 to 1.08 ; P=0.081 for the two irbesartan groups , respectively ) . The average blood pressure during the course of the study was 144/83 mm Hg in the placebo group , 143/83 mm Hg in the 150-mg group , and 141/83 mm Hg in the 300-mg group ( P=0.004 for the comparison of systolic blood pressure between the placebo group and the combined irbesartan groups ) . Serious adverse events were less frequent among the patients treated with irbesartan ( P=0.02 ) . CONCLUSIONS Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria The purpose of this study was to evaluate the long-term safety and efficacy of moexipril , a non-sulphydryl angiotensin converting enzyme inhibitor , alone or in combination with hydrochlorothiazide in older patients with hypertension . One hundred and seventy two hypertensive men and women , 65 - 80 years old , with seated DBP between 95 and 114 mm Hg were studied . The study was a 2 year , multicentre ( 12 centres ) , open-label protocol of moexipril monotherapy or combination therapy ( with hydrochlorothiazide ) .  Blood pressure , pulse rate , weight , adverse effects and laboratory studies were assessed following moexipril at 7.5 or 15 mg once daily or 7.5 or 15 mg daily in combination with 25 mg of hydrochlorothiazide if the seated DBP remained > or = 90 mm Hg on moexipril monotherapy . The primary measure of efficacy was a change from baseline in seated DBP . Secondary outcome measures included changes in seated DBP , pulse rate , laboratory parameters and adverse side-effects . Following 1 year of therapy in 135 patients , the BP fell 16/14 mm Hg among patients receiving moexipril monotherapy and 27/17 mm Hg for those receiving combined therapy compared with baseline ( P < 0.001 for both ) . After 2 years of treatment , reductions were similar in 120 patients . Nineteen patients ( 11 % ) were prematurely withdrawn from the study because of inadequate therapeutic response and 28 ( 16 % ) because of adverse experiences . There were no significant changes in pulse rate or postural reductions in BP on either moexipril monotherapy or combination treatment . Three adverse side-effects occurred at a frequency exceeding 2 % that were possibly or probably attributable to moexipril or combination therapy : hypotension ( 2 % ) , dizziness ( 6 % ) and increased cough ( 12 % ) . There were no clinical ly relevant mean group changes from baseline laboratory values in the treatment groups . In conclusion , these long-term data demonstrate that moexipril , either alone or in combination with hydrochlorothiazide , has long-term anti-hypertensive efficacy and is generally well tolerated in elderly patients with hypertension Although limited numbers of elderly subjects have occasionally been included in population -based studies , only a few studies have been conducted specifically on elderly hypertensives , and practically none at a population level . We studied 655 hypertensive subjects from a cohort of 2,254 elderly subjects . The intervention consisted of the creation of a Hypertension Out patients ' Clinic under our auspices but with complete co-operation from general practitioners , r and omizing the identified hypertensive patients into pre-established therapeutic drug regimens , and early follow-up recording of mortality for 7 years . The drugs used were clonidine ( n = 61 ) , nifedipine ( n = 146 ) and the fixed combination of atenolol+chlorthalidone ( n = 144 ) ; 304 subjects underwent " free therapy " by their personal physicians without any special intervention . There were 1,404 normotensive subjects . Overall 7-year follow-up mortality was 34.9 % in the hypertensive subjects receiving " free therapy " , 22.5 % in those receiving " special care " , and 24.2 % in the normotensives . Cardiovascular mortality was respectively 23.7 % , 12.2 % , and 12.0 % . Overall and cardiovascular annual cumulative mortality were significantly lower in the < < special therapy > > than in the < < free therapy > > group . The fixed combination of atenolol and chlorthalidone  reduced mortality below that of the normotensives , independent of other cardiovascular risk factors A r and omised trial of the treatment of hypertension in 884 patients aged 60 to 79 years at the onset showed a reduction of 18/11 mm Hg in blood pressure over a mean follow up period of 4.4 years . The principal antihypertensive agents were atenolol and bendrofluazide . There was a reduction in the rate of fatal stroke in the treatment group to 30 % of that in the control group ( 95 % confidence interval 11 - 84 % , p less than 0.025 ) . The rate of all strokes ( fatal and non-fatal ) in the treatment group was 58 % of that in the control group ( 95 % confidence interval 35 - 96 % , p less than 0.03 ) . The incidence of myocardial infa rct ion and total mortality was unaffected by treatment . Question naires completed by the patients and their relatives failed to identify any differences in symptoms that were likely to be due to treatment BACKGROUND Characteristics such as age and race are often cited as determinants of the response of blood pressure to specific antihypertensive agents , but this clinical ly important issue has not been examined in sufficiently large trials , involving all st and ard treatments , to determine the effect of such factors . METHODS In a r and omized , double-blind study at 15 clinics , we assigned 1292 men with diastolic blood pressures of 95 to 109 mm Hg , after a placebo washout period , to receive  placebo or one of six drugs : hydrochlorothiazide ( 12.5 to 50 mg per day ) , atenolol ( 25 to 100 mg per day ) , captopril ( 25 to 100 mg per day ) , clonidine ( 0.2 to 0.6 mg per day ) , a sustained-release preparation of diltiazem ( 120 to 360 mg per day ) , or prazosin ( 4 to 20 mg per day ) . The drug doses were titrated to a goal of less than 90 mm Hg for maximal diastolic pressure , and the patients continued to receive therapy for at least one year . RESULTS The mean ( + /- SD ) age of the r and omized patients was 59 + /- 10 years , and 48 percent were black . The average blood pressure at base line was 152 + /- 14/99 + /- 3 mm Hg . Diltiazem therapy  had the highest rate of success : 59 percent of the treated patients had reached the blood-pressure goal at the end of the titration phase and had a diastolic blood pressure of less than 95 mm Hg at one year .  Atenolol  was successful by this definition in 51 percent of the patients , clonidine in 50 percent , hydrochlorothiazide in 46 percent , captopril in 42 percent , and prazosin in 42 percent ; all these agents were superior to placebo ( success rate , 25 percent ) . Diltiazem ranked first for younger blacks ( < 60 years ) and older blacks ( > or = 60 years ) , among whom the success rate was 64 percent , captopril for younger whites ( success rate , 55 percent ) , and atenolol for older whites ( 68 percent ) . Drug intolerance was more frequent with clonidine ( 14 percent ) and prazosin ( 12 percent ) than with the other drugs . CONCLUSIONS Among men , race and age have an important effect on the response to single-drug therapy for hypertension . In addition to cost and quality of life , these factors should be considered in the initial choice of a drug In 1972 - -1973 , 785 symptom-free men , aged 40 to 49 years , without target organ damage , with systolic blood pressures between 150 and 179 mm Hg and diastolic blood pressure below 110 mm Hg , were assigned at r and om to one of two groups : ( 406 to a drug treatment group and 379 to a control group ) for a five-year controlled drug treatment trial to evaluate the effect of therapy on cardiovascular complications . Drug treatment started with hydrochlorothiazide . If systolic blood pressure remained above 140 mm Hg and /or diastolic blood pressure above 90 mm Hg , alphamethyldopa was added . If there were side effects , methyldopa was replaced with propranolol . The control group was not given a placebo . The mean observation time was 66 months ( range 60 to 78 months ) . A difference in blood pressure between groups of about 17 mm Hg systolic and 10 mm Hg diastolic was maintained throughout the study . The study protocol had a rather low " ethical " blood pressure roof , 180 mm Hg systolic and /or 110 mm Hg diastolic . Seventeen percent of the control group had an increase in blood pressure above this level during the trial , and drug treatment was started . There was no effect on major cardiovascular morbidity comparing groups as established by r and omization , with 18 events in the treatment group and 20 events in the control group . There was no difference between the groups in total mortality and mortality from cardiovascular events . However , in the subgroups with diastolic blood pressure greater than or equal to 100 mm Hg before r and omization , there was a probable reduction in total morbidity from cardiovascular events in favor or the group receiving drug therapy , 7.6 and 16.4 percent events in the treated and control groups , respectively . Cerebrovascular events occurred only in the control group , 7 versus 0 . Two cases of fatal aortic aneurysms also occurred in the control group . Other " pressure " complications , such as marked left ventricular hypertrophy in the electrocardiogram and left ventricular failure , occurred only in the control group . However , regarding coronary heart disease , including sudden death , the incidence tended to be higher in the treated group , although it was not statistically significant . Only 13 men ( 1.7 percent ) failed to meet for regular examinations . At the end of the study these men were also followed up with regard to possible cardiovascular events Abstract Morbidity , mortality , and target organ function have been followed in a double-blind study of a predominantly Negro clinic population with mild to moderately severe hypertension over a 2-year period . Patients were placed r and omly on either hypotensive drug therapy ( reserpine , thiazide , guanethedine ) or matched placebos . There were 6 treatment failures among 45 patients in the treatment group and 19 failures among 42 patients in the placebo group . All but one of the failures in the placebo group improved or cleared upon early institution of appropriate hypertensive and supportive therapy . Abnormalities in carbohydrate metabolism and serum uric acid levels were found in patients receiving long-term thiazide therapy .  Hypertensive disease in the Negro population of Baltimore is a serious , life-threatening condition . Our study provides evidence of the need for continuous close supervision , and the provision of organized teams devoted to the care , of such a population The main aim of the trial was to determine whether drug treatment of mild hypertension ( phase V diastolic pressure 90 - 109 mm Hg ) reduced the rates of stroke , of death due to hypertension , and of coronary events , in men and women aged 35 - 64 years . A total of 17,354 patients was recruited , and 85,572 patient-years of observation accrued . Patients were r and omly allocated at entry to take bendrofluazide or placebo , or propranolol or placebo . The stroke rate was reduced with treatment ( 60 strokes , vs 109 in the placebo groups ) , being 1.4 and 2.6 per 1,000 patient-years of observation , respectively ( p less than 0.01 ) , but overall rates of coronary events were not different ( 222 with treatment and 234 with placebos ) . The incidence of all cardiovascular events was reduced with treatment ( 286 events , vs 352 with placebos ; p less than 0.05 ) . For rates of mortality from all causes , treatment made no difference . Several post hoc analyses of subgroup results were performed . The all-cause mortality was reduced in men on treatment ( 157 deaths , vs 181 in placebo groups ) but increased in women on treatment ( 91 deaths , vs 72 with placebos ) ; this difference between the sexes was significant ( p = 0.05 ) . The reduction in stroke rate was greater with bendrofluazide than with propranolol ( p = 0.002 ) . The rate of strokes was reduced in both smokers and non-smokers taking bendrofluazide , but only in non-smokers taking propranolol ; this difference between the drugs was significant ( p = 0.03 ) . The coronary-event rate was not reduced by bendrofluazide , whatever the smoking habit , nor in smokers taking propranolol , but it was reduced in non-smokers taking propranolol . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objective : To compare the effectiveness and tolerability of hydrochlorothiazide , atenolol , nitrendipine , and enalapril in patients with mild to moderate hypertension . Design : R and omised multicentre trial over 48 weeks with double blind comparison of treatments . Setting : 48 centres in four countries . Patients : 868 patients with essential hypertension ( diastolic blood pressure 95 - 120 mm Hg ) Interventions : Initial treatment ( step 1 ) consisted of 12.5 mg hydrochlorothiazide ( n=215 ) , 25 mg atenolol ( n=215 ) , 10 mg nitrendipine ( n=218 ) , or 5 mg enalapril ( n=220 ) once daily . If diastolic blood pressure was not reduced to < 90 mm Hg within four weeks , doses were increased to 25 mg , 50 mg , 20 mg , 10 mg , respectively , once daily ( step 2 ) and after two more weeks to twice daily ( step 3 ) . The eight week titration phase was followed by an additional 40 weeks for patients who had reached the target diastolic pressure . Main outcome measure : Blood pressure by means of an automatic device with repeated measurements . Results : After eight weeks the response rate for  atenolol  ( 63.7 % ) was significantly higher than for enalapril ( 50.0 % ) , hydrochlorothiazide ( 44.7 % ) , or nitrendipine ( 44.5 % ) . After one year atenolol was still more effective ( 48.0 % ) than hydrochlorothiazide ( 35.4 % ) and nitrendipine ( 32.9 % ) , but not significantly better than enalapril ( 42.7 % ) . The treatment related dropout rate was higher ( P<0.001 ) in the nitrendipine group ( n=28 ) . Conclusions : There is no evidence of superiority for antihypertensive effectiveness or tolerability of the “ new ” classes of antihypertensives ( calcium channel blockers and angiotensin converting enzyme inhibitors ) . As these drugs are now widely used as treatment of first choice , our results further emphasise the need for studies confirming that they also reduce morbidity and mortality , as has been shown for diuretics and ß blockers . Key messages Calcium channel blockers and angiotensin converting enzyme inhibitors as initial monotherapy in the treatment of hypertension Reduction in mortality has been shown only with established ß blockers and diuretics Comparison of treatment with hydrochlorothiazide , atenolol , nitrendipine , and enalapril showed no superiority of the new drug classes Atenolol was the most effective drug , while nitrendipine showed the highest drop out rat  Elderly patients  respond better to hydrochlorothiazide and nitrendipine , and women better to enalapril , although in both subgroups the highest rate of response was with & NA ; Isolated systolic hypertension ( ISH ) is a definite risk factor for cardiovascular complications ( i.e. , cardiac failure , coronary artery disease , and stroke ) independent of diastolic elevation . The prevalence of ISH is estimated to be approximately 15‐20 % in the population above the age of 60 years , and increases with advancing age . The Systolic Hypertension in the Elderly ( SHELL ) study is planned to evaluate the efficacy and tolerability of lacidipine , matched with the diuretic chlorthalidone , in treatment of ISH in elderly hypertensive patients ( EHP ) . One hundred fifteen Italian centers will participate in the study . Fifty centers are associated with the Società Italiana di Geriatria Ospedaliera and 65 centers are departments of internal medicine or outpatient clinics for management of hypertension . A total of 4,800 patients will be enrolled in the trial . Two subprojects will consist of periodical echocardiographic evaluation and 24‐h ambulatory blood pressure monitoring . The primary end point of the SHELL study is the incidence of cardiovascular and cerebrovascular events in EHP with ISH , treated with either lacidipine or chlorthalidone . In particular , the SHELL trial is intended to determine whether lacidipine treatment will significantly reduce fatal myocardial events and total cardiovascular mortality Background A common method of recruiting for r and omized trials is to send letters to potentially eligible patients inviting them to a screening appointment . In 3 consecutive UK studies the proportion attending from those invited fell from 49 % [ 1 ] in 1994 - 1997 and 42%[2 ] in 1998 - 2001 to 13 % at the beginning of an ongoing study in 2007 . Procedures were similar in the 3 trials except that in 2007 the Patient Information Leaflet ( PIL ) was enclosed with the invitation letter . In order to underst and whether the contents and /or style of invitation would explain the declining trend , 2 separate r and omized comparisons were undertaken during the recruitment for the ongoing study PREVALENCE OF  HYPERTENSION IN ELDERLY JAPANESE PATIENTS : Data collected from post-mortem information at the Tokyo Metropolitan Geriatric Hospital showed that the overall prevalence of hypertension in Japanese patients aged over 60 years was 53 % ; one-third of these elderly hypertensives had isolated systolic hypertension . Isolated systolic and systolodiastolic hypertension were each associated with a similar degree of increased atherosclerosis and cardiovascular complications . In a placebo-controlled study antihypertensive treatment produced a reduction in withdrawal from treatment in elderly patients with mild hypertension . INTERIM TRIAL RESULTS : Some interim results have been obtained from a new trial which is currently under way in Japan , the National Intervention Cooperative Study for the Treatment of Elderly Hypertensives , a long-term study comparing the effects of a calcium antagonist ( nicardipine ) and a thiazide diuretic ( trichlormethiazide ) on cardiovascular complications in elderly patients with mild to moderate hypertension Background and Purpose : & bgr;‐Blockers prevent vascular events in patients after myocardial infa rct ion and lower blood pressure , the main risk factor for stroke . Hence , we assessed the effects of atenolol on the occurrence of death from vascular causes , stroke , or myocardial infa rct ion and on blood pressure in patients after a transient ischemic attack or nondisabling ischemic stroke . Methods : In a double‐blind , placebo‐controlled r and omized clinical trial we studied the occurrence of the outcome event death from vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion and the outcome event fatal or nonfatal stroke as well as blood pressure on follow‐up . A total of 1,473 aspirin‐treated patients with transient ischemic attack or nondisabling ischemic stroke were r and omized to 50 mg atenolol daily or placebo . The mean follow‐up was 2.6 years . Results : Patients on atenolol had a risk of 97/732 ( 13.3 % ) for the combined outcome event versus a risk of 95/741 ( 12.8 % ) for those on placebo ( adjusted hazard ratio , 1.00 ; 95 % confidence interval , 0.76‐1.33 ) . The adjusted hazard ratio for fatal or nonfatal stroke was 0.82 ( 95 % confidence interval , 0.57‐1.19 ) . More patients on & bgr;‐blocker ( 153 ) reported adverse effects than on placebo ( 103 ) . At the first follow‐up visit after r and omization ( median at 4 months ) systolic blood pressure in the atenolol group had dropped by 8.0 mm Hg compared with 2.2 mm Hg in the placebo group ( difference , 5.8 mm Hg ; 95 % confidence interval , 2.9‐8.6 mm Hg ) . For diastolic blood pressure this difference was 2.9 mm Hg ( 95 % confidence interval , 1.5‐4.4 mm Hg ) . Conclusions : Our data neither confirm nor rule out that atenolol prevents important vascular events in patients after transient ischemic attack or nondisabling ischemic stroke , given the modest effect on blood pressure , the restrictions in patient selection , and the limited number of patient‐years . ( Stroke 1993;24:543‐548 BACKGROUND Drugs that inhibit the renin-angiotensin-aldosterone system benefit patients at risk for or with existing cardiovascular disease . However , evidence for this effect in Asian population s is scarce . We aim ed to investigate whether addition of an angiotensin receptor blocker , valsartan , to conventional cardiovascular treatment was effective in Japanese patients with cardiovascular disease . METHODS We initiated a multicentre , prospect i ve , r and omised controlled trial of 3081 Japanese patients , aged 20 - 79 years , ( mean 65 [ SD 10 ] years ) who were undergoing conventional treatment for hypertension , coronary heart disease , heart failure , or a combination of these disorders . In addition to conventional treatment , patients were assigned either to valsartan ( 40 - 160 mg per day ) or to other treatment without angiotensin receptor blockers . Our primary endpoint was a composite of cardiovascular morbidity and mortality . Analysis was by intention to treat . The study was registered at clintrials.gov with the identifier NCT00133328 . FINDINGS After a median follow-up of 3.1 years ( range 1 - 3.9 ) the primary endpoint was recorded in fewer individuals given valsartan than in controls ( 92 vs 149 ; absolute risk 21.3 vs 34.5 per 1000 patient years ; hazard ratio 0.61 , 95 % CI 0.47 - 0.79 , p=0.0002 ) . This difference was mainly attributable to fewer incidences of stroke and transient ischaemic attack ( 29 vs 48 ; 0.60 , 0.38 - 0.95 , p=0.028 ) , angina pectoris ( 19 vs 53 ; 0.35 , 0.20 - 0.58 , p<0.0001 ) , and heart failure ( 19 vs 36 ; 0.53 , 0.31 - 0.94 , p=0.029 ) in those given valsartan than in the control group . Mortality or tolerability did not differ between groups . INTERPRETATION The addition of valsartan to conventional treatment prevented more cardiovascular events than supplementary conventional treatment . These benefits can not be entirely explained by a difference in blood pressure control Background This long-term , multicenter , r and omized , double-blind , placebo-controlled , 2 × 2 factorial , angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients . Methods and Results There were a total of 460 patients : 230 received simvastatin and 230 , a simvastatin placebo , and  229 received enalapril and 231 , an enalapril placebo ( some subjects received both drugs and some received a double placebo ) . Mean baseline measurements were as follows : cholesterol level , 5.20 mmol/L ; triglyceride level , 1.82 mmol/L ; HDL , 0.99 mmol/L ; and LDL , 3.36 mmol/L. Average follow-up was 47.8 months . Changes in quantitative coronary angiographic measures between simvastatin and placebo , respectively , were as follows : mean diameters , −0.07 versus −0.14 mm ( P = 0.004 ) ; minimum diameters , −0.09 versus −0.16 mm ( P = 0.0001 ) ; and percent diameter stenosis , 1.67 % versus 3.83 % ( P = 0.0003 ) . These benefits were not observed in patients on enalapril when compared with placebo . No additional benefits were seen in the group receiving both drugs . Simvastatin patients had less need for percutaneous transluminal coronary angioplasty ( 8 versus 21 events;P = 0.020 ) , and fewer enalapril patients experienced the combined end point of death/myocardial infa rct ion/stroke ( 16 versus 30;P = 0.043 ) than their respective placebo patients . Conclusions This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients . The implication s of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain , but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere The present study of primary prevention in white men aged 40 to 64 years attempts to investigate whether a beta-blocker given as initial antihypertensive treatment would lower total mortality to a greater extent than thiazide diuretics .  Patients were r and omized to metoprolol ( n = 1609 , 8110 patient-years ) or a thiazide diuretic ( n = 1625 , 8070 patient-years ) . The median follow-up time was 4.2 years . The mean dose of metoprolol was 174 mg/d , and of thiazide diuretics , 46 mg/d of hydrochlorothiazide or 4.4 mg/d of bendroflumethiazide . Identical control of blood pressure was achieved using a fixed therapeutic schedule . Total mortality was significantly lower for metoprolol than for thiazide diuretics because of fewer deaths from coronary heart disease and stroke . Total mortality was also significantly lower in smokers r and omized to metoprolol .  The benefit demonstrated in patients treated with metoprolol seems to have important implication s for clinical practice The Hypertension Optimal Treatment ( HOT ) Study is an ongoing prospect i ve , r and omized , multicenter trial conducted in 26 countries . Its two main aims are 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 and the effects on morbidity and mortality of a low dose , 75 mg daily , of acetylsalicylic acid ( ASA , aspirin ) compared with placebo .  Altogether 19,193 patients have been recruited and r and omized and one-year data are now available for all patients . This is a report on the blood pressures achieved , the tolerability and other available data after 12 months of follow-up of all patients . Special reference will be given to the subgroup of elderly patients ( > or = 65 years , n = 6,113 ) as compared to younger patients ( < 65 years , n = 13,080 ) . On average , the target group < or = 90 mmHg in diastolic blood pressure has reached 86 mmHg , the target group < or = 85 mmHg has reached 83 mmHg and the target group < or = 80 mmHg has reached 81 mmHg . The percentage of patients that has obtained their target blood pressures is 84 % in the target group < or = 90 mmHg , 72 % in the target group < or = 85 mmHg and 57 % in the target group < or = 80 mmHg at 12 months of follow-up . In the elderly subgroup ( > or = 65 years of age ) the percentage of patients at target is higher for all target groups , being 86 , 76 and 61 % , respectively , at 12 months . Antihypertensive treatment is initiated with a calcium antagonist , felodipine , at a dose of 5 mg once 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 dose adjustments are made in accordance with a set protocol . As a fifth and final step a diuretic may be added . Side effects have been relatively few in this large multinational series of intensively treated hypertensive patients . Only ankle edema , 2.6 % and 3.0 % , and coughing , 1.3 % and 0.8 % , in young and elderly patients , respectively , exceed a frequency of 1 % , and 88 % of all patients are still taking their baseline therapy felodipine after one year . The one-year data presented here indicate that it should be possible to fulfill the primary aims of the HOT Study Serum glucose levels , triglyceride levels , and body weight are reported from a controlled drug trial in men , aged 40 to 49 , with uncomplicated mild hypertension . The drug treatment started with hydrochlorothiazide alone , and methyldopa was added when necessary . If side effects occurred , methyldopa was replaced by propranolol . No detailed advice about diet , smoking , or weight reduction was given to any group . The untreated control subjects had a small increase in serum glucose levels during five years , from 6.08 to 6.21 mmol/liter . Those treated with hydrochlorothiazide alone and those treated with hydrochlorothiazide plus methyldopa had a small increase in serum glucose levels of the same order as that in the control subjects . However , those receiving the thiazide/propranolol combination experienced a sizeable increase in glucose levels , from 5.96 to 6.53 mmol/liter ( p less than 0.001 ) . This increase was significantly greater than the increase in the other groups ( p less than 0.001 ) . The thiazide/propranolol group also showed a significant increase in serum triglyceride levels ( p less than 0.05 ) . There was no difference in serum potassium levels in the different drug groups . The results indicate that moderate thiazide doses do not have significant effects on serum glucose levels in this age group . Propranolol in combination with thiazide seems to increase the level of serum glucose A feasibility trial to investigate the practicality of determining the advantages and disadvantages of prompt pharmacologic treatment for mild hypertension was jointly funded by the Veterans Administration and the National Heart , Lung and Blood Institute . Its clinical phase has been completed , and it demonstrated 1 . that the required relatively young asymptomatic population could be enrolled in the study and 2 . that it could be persuaded to adhere to the protocol for 2 years ; however , it was evident that intensive efforts would be required in both areas . The feasibility trial screened almost 120,000 potential subjects over a period of 16 months to r and omize about 1,000 subjects at four clinical centers . These men and women were 21 to 50 years old , had diastolic pressures from 85 to 105 mm Hg as out patients , and had no evidence of cardiovascular renal abnormalities . They were r and omized in double-blind fashion into active drug therapy and placebo groups . Stepped care therapy involved 50 mg chlorthalidone ( Step 1 ) , 100 mg chlorthalidone ( Step 2 ) and 100 chlorthalidone plus 0.25 mg reserpine ( Step 3 ) . Death , myocardial infa rct ion , stroke , angina pectoris , and congestive heart failure were the " major " morbid events that were looked for ; also recorded were " minor " morbid events consisting primarily of electrocardiographic arrhythmias . The development of significant hypertension was considered a treatment failure . Side effects were carefully tabulated in both active drug and placebo groups . The study revealed an average drop in diastolic pressure of almost 12 mm Hg for active drug group and less than half of that for the placebo group ; once established 6 months after r and omization , the new pressure levels persisted almost without change throughout the study . Although the feasibility trial was not design ed to answer the primary question regarding the benefits of treatment , the events were tabulated for each group . A total of 12 placebo-treated subjects developed significant hypertension and were put on active drug . There was not a significant difference between the two groups in the incidence of " major " morbid events ; a total of eight active and five placebo patients developed myocardial infa rct ion or died suddenly . There , however , was an excess of arrhythmias among the active drug subjects ( 17 in the active group versus 8 in the placebo group on the basis of preliminary data ) . Finally , there were twice as many side effects and 20 times as many chemical abnormalities among the active as among the placebo subjects . A protocol for a full scale study of the benefits of pharmacologic therapy in mild hypertensives has been prepared and is ready for implementation as needed ; it involves relatively minor modifications of the protocol tested in the feasibility trial OBJECTIVE To compare the rate of progression of mean maximum intimal-medial thickness ( IMT ) in carotid arteries , using quantitative B-mode ultrasound imaging , during  antihypertensive therapy with isradipine vs hydrochlorothiazide . DESIGN R and omized , double-blind , positive-controlled trial . SETTING Nine medical center clinics . POPULATION A total of 883 patients with baseline mean + /- SD systolic and diastolic blood pressure ( SBP and DBP , respectively ) of 149.7 + /- 16.6 and 96.5 + /- 5.1 mm Hg , age of 58.5 + /- 8.5 years , and maximum IMT of 1.17 + /- 0.20 mm . INTERVENTIONS Twice daily doses of isradipine ( 2.5 - 5.0 mg ) or hydrochlorothiazide ( 12.5 - 25 mg ) . MAIN OUTCOME MEASURE ( PRIMARY END POINT ) : Rate of progression of mean maximum IMT in 12 carotid focal points over 3 years . RESULTS There was no difference in the rate of progression of mean maximum IMT between isradipine and hydrochlorothiazide over 3 years ( P=.68 ) . There was a higher incidence of major vascular events ( eg , myocardial infa rct ion , stroke , congestive heart failure , angina , and sudden death ) in isradipine ( n=25 ; 5.65 % ) vs hydrochlorothiazide ( n=14 ; 3.17 % ) ( P=.07 ) , and a significant increase in nonmajor vascular events and procedures ( eg , transient ischemic attack , dysrhythmia , aortic valve replacement , and femoral popliteal bypass graft ) in isradipine ( n=40 ; 9.05 % ) vs hydrochlorothiazide ( n=23 ; 5.22 % ) ( P=.02 ) . At 6 months , mean DBP decreased by 13.0 mm Hg in both groups , and mean SBP decreased by 19.5 mm Hg in hydrochlorothiazide and 16.0 mm Hg in isradipine ( P=.002 ) ; the difference in SBP between the 2 groups persisted throughout the study but did not explain the increased incidence of vascular events in patients treated with isradipine . CONCLUSION The rate of progression of mean maximum IMT in carotid arteries , the surrogate end point in this study , did not differ between the 2 treatment groups . The increased incidence of vascular events in patients receiving isradipine compared with hydrochlorothiazide is of concern and should be studied further 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 The objective of the study is to compare fatal and nonfatal cardiovascular endpoints in hypertensive patients r and omised to the calcium-channel blocker , nifedipine GITS or a thiazide diuretic , co-amilozide . A total of 6592 patients from nine countries ( UK , France , Israel , Spain , Italy , The Netherl and s , Sweden , Denmark and Norway ) will be recruited , aged 55 - 80 and with a blood pressure ( BP ) > or = 150/95 or > or = 160 mm Hg ( systolic ) . All patients will have at least one other major cardiovascular risk factor . Patients will be minimised by country and risk factors and r and omised to double-blind treatment with either nifedipine GITS or diuretic . After a single dose titration , additional treatment will be atenolol or enalapril ( where beta-blockade is contra-indicated ) . After achieving a target BP of 140/90 mm Hg patients will be followed for a total of 3 years . Primary endpoints are myocardial infa rct ion , stroke , subarachnoid haemorrhage , heart failure and sudden cardiac death . The study has a power of 80 % at 5 % significance to detect a difference between 8 % event rate over 3 years in diuretic-treated patients and 6 % in those receiving nifedipine Men aged 40 - 64 years with mild to moderate hypertension [ diastolic blood pressure ( DBP ) 100 - 130 mmHg ] were r and omized to treatment with a  diuretic ( n = 3272 ) or a  beta-blocker ( n = 3297 ) , with additional drugs if necessary , to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease ( CHD ) events and death .  Patients with previous CHD , stroke or other serious diseases , or with contraindications to diuretics or beta-blockers were excluded . If normotension ( DBP less than 95 mmHg ) was not achieved by monotherapy , other antihypertensive drugs were added , but the two basic drugs were not crossed over . Patients were assessed at 6-monthly intervals . The mean follow-up for end-points was 45.1 months . Blood pressure ( BP ) side effects and end-points were recorded in a st and ardized manner . Entry characteristics and the BP reduction achieved were very similar in both treatment groups . All analyses were made on an intention-to-treat basis . The incidence of CHD did not differ between the two treatment groups . The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group . Total mortality and the total number of end-points were similar in both groups . The percentage of patients withdrawn due to side effects was similar , whereas the number of reported symptoms , according to a question naire , was higher for patients on beta-blockers . The incidence of diabetes did not differ between the two groups . Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers , and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD . Beta-blockers and thiazide diuretics were approximately equally well tolerated . The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group . Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications , including CHD , to a different extent ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle – brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute C and esartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease : Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A R and omized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Sc and inavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Sc and inavian Cardiac Outcomes Trial — Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : C And esartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease — EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy C and esartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease  EXPLOR : Amlodipine – Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine – Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infa rct ion in 52 Countries INVEST : INternational VErapamil SR/T Tr and olapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention : an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : r and omized controlled trials RF : risk factor ROADMAP : R and omized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker C and esartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly : Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan R and omised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospect i ve Diabetes Study VADT : Veterans ' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization # # # 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension ( ESH ) and the European Society of Cardiology Hypertension is the most common condition seen in primary care and leads to myocardial infa rct ion , stroke , renal failure , and death if not detected early and treated appropriately . Patients want to be assured that blood pressure ( BP ) treatment will reduce their disease burden , while clinicians want guidance on hypertension management using the best scientific evidence . This report takes a rigorous , evidence -based approach to recommend treatment thresholds , goals , and medications in the management of hypertension in adults . Evidence was drawn from r and omized controlled trials , which represent the gold st and ard for determining efficacy and effectiveness . Evidence quality and recommendations were grade d based on their effect on important outcomes . There is strong evidence to support treating hypertensive persons aged 60 years or older to a  BP goal  of less than 150/90 mm Hg and hypertensive persons 30 through 59 years of age to a diastolic goal of less than 90 mm Hg ; however , there is insufficient evidence in hypertensive persons younger than 60 years for a systolic goal , or in those younger than 30 years for a diastolic goal , so the panel recommends a BP of less than 140/90 mm Hg for those groups based on expert opinion . The same thresholds and goals are recommended for hypertensive adults with diabetes or nondiabetic chronic kidney disease ( CKD ) as for the general hypertensive population younger than 60 years . There is moderate evidence to support initiating drug treatment with an angiotensin-converting enzyme inhibitor , angiotensin receptor blocker , calcium channel blocker , or thiazide-type diuretic in the nonblack hypertensive population , including those with diabetes . In the black hypertensive population , including those with diabetes , a calcium channel blocker or thiazide-type diuretic is recommended as initial therapy . There is moderate evidence to support initial or add-on antihypertensive therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in persons with CKD to improve kidney outcomes . Although this guideline provides evidence -based recommendations for the management of high BP and should meet the clinical needs of most patients , these recommendations are not a substitute for clinical judgment , and decisions about care must carefully consider and incorporate the clinical characteristics and circumstances of each individual patient
target: Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity .
  All-cause mortality and coronary heart disease were not reduced .
  There is lack of good evidence on withdrawal due to adverse events .
background: BACKGROUND Hypertension is an important risk factor for adverse cardiovascular events including stroke , myocardial infa rct ion , heart failure and renal failure .
  The main goal of treatment is to reduce these events .
  Systematic review s have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older .
  We wanted to know what the effects of therapy are in people 18 to 59 years of age .
  OBJECTIVES To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension .
  To quantify effects on cardiovascular mortality plus morbidity ( including cerebrovascular and coronary heart disease mortality plus morbidity ) , withdrawal due adverse events and estimate magnitude of systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) lowering at one year .