title: The ACCESS Study: Evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors 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 Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack Beta-adrenergic blockade after stroke. A preliminary closed cohort study. Hypotensive therapy in stroke survivors. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study Comparative Effects of Ramipril on Ambulatory and Office Blood Pressures: A HOPE Substudy PROGRESS - Perindopril Protection Against Recurrent Stroke Study: characteristics of the study population at baseline. Progress Management Committee. Low dose beta blockade in acute stroke ("BEST" trial): an evaluation. Multiple risk factor intervention trial. Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. Blood pressure, stroke, and coronary heart disease: Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias Randomised trial of treatment of hypertension in elderly patients in primary care. Blood pressure and risk of stroke in patients with cerebrovascular disease Effects of antihypertensive agents on circadian blood pressure in hypertensive patients with previous brain infarction Mortality and Morbidity Results from the European Working Party on High Blood Pressure in the Elderly Trial
abstract: Background and Purpose — The Acute C and esartan Cilexetil Therapy in Stroke Survivors ( ACCESS ) study was design ed to assess the safety of modest blood pressure reduction by c and esartan cilexetil in the early treatment of stroke . The study was also design ed to provide an estimate of the number of cases required to perform a larger phase III efficacy study . Methods — Five hundred patients were recruited in a prospect i ve , double-blind , placebo-controlled , r and omized , multicenter phase II study . Results — This safety trial was stopped prematurely when 342 patients ( 339 valid ) had been r and omized because of an imbalance in end points .  Demographic data , cardiovascular risk factors , and blood pressure on admission , on study onset , and within the whole study period were not significantly different between the 2 groups . However , the cumulative 12-month mortality and the number of vascular events differed significantly in favor of the c and esartan cilexetil group ( odds ratio , 0.475 ; 95 % CI , 0.252 to 0.895 ) . There were no significant differences in concomitant medication and in number or type of side effects . Conclusions — Although the mechanisms by which angiotensin type 1 ( AT1 ) receptor blockade affects cardiovascular morbidity and mortality are still unresolved , the present study shows that early neurohumoral inhibition has similar beneficial effects in cerebral and in myocardial ischemia . The fact that no cardiovascular or cerebrovascular event occurred as a result of hypotension is of significant clinical importance . When there is need for or no contraindication against early antihypertensive therapy , c and esartan cilexetil is a safe therapeutic option according to the ACCESS results 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 Blood pressure is a determinant of the risk of stroke among both hypertensive and non-hypertensive individuals with cerebrovascular disease . However , there is uncertainty about the efficacy and safety of blood-pressure-lowering treatments for many such patients . The perindopril protection against recurrent stroke study ( PROGRESS ) was design ed to determine the effects of a blood-pressure-lowering regimen in hypertensive and non-hypertensive patients with a history of stroke or transient ischaemic attack . METHODS 6105 individuals from 172 centres in Asia , Australasia , and Europe were r and omly assigned active treatment ( n=3051 ) or placebo ( n=3054 ) . Active treatment comprised a flexible regimen based on the angiotensin- converting-enzyme inhibitor perindopril ( 4 mg daily ) , with the addition of the diuretic indapamide at the discretion of treating physicians . The primary outcome was total stroke ( fatal or non-fatal ) . Analysis was by intention to treat . FINDINGS Over 4 years of follow up , active treatment reduced blood pressure by 9/4 mm Hg . 307 ( 10 % ) individuals assigned active treatment suffered a stroke , compared with 420 ( 14 % ) assigned placebo ( relative risk reduction 28 % [ 95 % CI 17 - 38 ] , p<0.0001 ) . Active treatment also reduced the risk of total major vascular events ( 26 % [ 16 - 34 ] ) . There were similar reductions in the risk of stroke in hypertensive and non-hypertensive subgroups ( all p<0.01 ) . Combination therapy with perindopril plus indapamide reduced blood pressure by 12/5 mm Hg and stroke risk by 43 % ( 30 - 54 ) . Single-drug therapy reduced blood pressure by 5/3 mm Hg and produced no discernable reduction in the risk of stroke . INTERPRETATION This blood-pressure-lowering regimen reduced the risk of stroke among both hypertensive and non-hypertensive individuals with a history of stroke or transient ischaemic attack . Combination therapy with perindopril and indapamide produced larger blood pressure reductions and larger risk reductions than did single drug therapy with perindopril alone . Treatment with these two agents should now be considered routinely for patients with a history of stroke or transient ischaemic attack , irrespective of their blood pressure To collect background data for a prospect i ve clinical trial of beta-blocking agents in the prevention of deaths after stroke , the long-term prognosis in 60 patients discharged from a stroke unit on beta-blocker therapy  was compared with the outcome in 60 matched patients with stroke but without beta-blockers .  Matching included sex , age , type of stroke , and presence or absence of hypertension and cardiac failure . Thirteen patients ( 22 % ) in the beta-blocker group died during a median followup of 41 months . Of the 60 patients not on beta-blockade at discharge , 21 ( 35 % ) died during a median followup of 36 months . By life-table technique and log-rank test , the relative risk for death was 0.60:1.00 ( p = 0.14 ) . During followup , 12 recurrent strokes were observed in patients on beta-blockers and 19 in patients without beta-blockers ( relative risk 0.57:1.00 ; p = 0.12 ) . It appeared that the reduction in mortality could only marginally be ascribed to fewer deaths from myocardial infa rct ion ; other causes of death were also less frequent in beta-blocker-treated patients . The results emphasize that supplementary information on the effect of beta-blocking agents on mortality after stroke is needed before a larger trial of beta-blocker therapy in patients with manifest cerebrovascular disease can be initiated 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 BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors have been used for more than a decade to treat high blood pressure  , despite the lack of data from r and omised intervention trials to show that such treatment affects cardiovascular morbidity and mortality . The Captopril Prevention Project ( CAPPP ) is a r and omised intervention trial to compare the effects of ACE inhibition and conventional therapy on cardiovascular morbidity and mortality in patients with hypertension . METHODS CAPPP was a prospect i ve , r and omised , open trial with blinded endpoint evaluation . 10,985 patients were enrolled at 536 health centres in Sweden and Finl and . Patients aged 25 - 66 years with a measured diastolic blood pressure of 100 mm Hg or more on two occasions were r and omly assigned captopril or conventional antihypertensive treatment ( diuretics , beta-blockers ) . Analysis was by intention-to-treat . The primary endpoint was a composite of fatal and non-fatal myocardial infa rct ion , stroke , and other cardiovascular deaths . FINDINGS Of 5492 patients assigned captopril and 5493 assigned conventional therapy , 14 and 13 , respectively , were lost to follow-up . Primary endpoint events occurred in 363 patients in the captopril group ( 11.1 per 1000 patient-years ) and 335 in the conventional-treatment group ( 10.2 per 1000 patient-years ; relative risk 1.05 [ 95 % CI 0.90 - 1.22 ] , p=0 - 52 ) . Cardiovascular mortality was lower with captopril than with conventional treatment ( 76 vs 95 events ; relative risk 0.77 [ 0.57 - 1 - 04 ] , p=0.092 ) , the rate of fatal and non-fatal myocardial infa rct ion was similar ( 162 vs 161 ) , but fatal and non-fatal stroke was more common with captopril ( 189 vs 148 ; 1.25 [ 1 - 01 - 1 - 55 ] . p=0.044 ) . INTERPRETATION Captopril and conventional treatment did not differ in efficacy in preventing cardiovascular morbidity and mortality . The difference in stroke risk is probably due to the lower levels of blood pressure obtained initially in previously treated patients r and omised to conventional therapy BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure BACKGROUND The efficacy of new antihypertensive drugs has been question ed . We compared the effects of conventional and newer antihypertensive drugs on cardiovascular mortality and morbidity in elderly patients . METHODS We did a prospect i ve , r and omised trial in 6614 patients aged 70 - 84 years with hypertension ( blood pressure > or = 180 mm Hg systolic , > or = 105 mm Hg diastolic , or both ) . Patients were r and omly assigned conventional antihypertensive drugs ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) or newer drugs ( enalapril 10 mg or lisinopril 10 mg , or felodipine 2.5 mg or isradipine 2 - 5 mg daily ) . We assessed fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease . Analysis was by intention to treat . FINDINGS Blood pressure was decreased similarly in all treatment groups . The primary combined endpoint of fatal stroke , fatal myocardial infa rct ion , and other fatal cardiovascular disease occurred in 221 of 2213 patients in the conventional drugs group ( 19.8 events per 1000 patient-years ) and in 438 of 4401 in the newer drugs group ( 19.8 per 1000 ; relative risk 0.99 [ 95 % CI 0.84 - 1.16 ] , p=0.89 ) . The combined endpoint of fatal and non-fatal stroke , fatal and non-fatal myocardial infa rct ion , and other cardiovascular mortality occurred in 460 patients taking conventional drugs and in 887 taking newer drugs ( 0.96 [ 0.86 - 1.08 ] , p=0.49 ) . INTERPRETATION Old and new antihypertensive drugs were similar in prevention of cardiovascular mortality or major events . Decrease in blood pressure was of major importance for the prevention of cardiovascular events In the HOPE-trial , the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events . The benefit could only partly be attributed to the modest mean reduction of office blood pressure ( OBP ) during the study period ( 3/2 mm Hg ) . However , because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day , the 24-hour reduction of blood pressure may be underestimated based on OBP . Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent  24-hour ambulatory blood pressure ( ABP ) measurement  before r and omization and after 1 year . OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients . Ramipril did not significantly reduce OBP ( 8/2 mm Hg , P = NS ) or day ABP ( 6/2 mm Hg , P = NS ) after 1 year . Twenty-four – hour ABP was significantly reduced ( 10/4 mm Hg , P = 0.03 ) , mainly because of a more pronounced blood pressure lowering effect during nighttime ( 17/8 mm Hg , P < 0.001 ) . The night/day ratio was also significantly lowered in the ramipril  group . ABP shows greater falls , especially at night , than OBP during treatment with ramipril given once daily at bedtime . Although , OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies , the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may , to a larger extent than previously ascribed , relate to effects on blood pressure patterns over the 24-hour period OBJECTIVE The primary aim of the Perindopril Protection Against Recurrent Stroke Study ( PROGRESS ) is to determine the effects of a long-term angiotensin converting enzyme (ACE)-inhibitor-based blood-pressure-lowering regimen on the risk of stroke among patients with a history of stroke or transient ischaemic attack ( TIA ) . Secondary aims include investigation of the effects of treatment on total cardiovascular events , dementia and disability . DESIGN AND METHODS PROGRESS is a double-blind , placebo-controlled  r and omized trial . Patients were r and omly assigned to treatment with the ACE inhibitor perindopril ( and the diuretic indapamide for those with no definite indication or contraindication to treatment with a diuretic ) versus matching placebo(s ) . Both hypertensive and non-hypertensive patients were eligible for inclusion . Follow-up is scheduled for completion in 2001 . The study is being conducted in 172 centres in 10 countries ( Australia , Belgium , China , France , Italy , Irel and , Japan , New Zeal and , Sweden and the United Kingdom ) . RESULTS Recruitment was completed in November 1997 , with 6105 patients r and omized . Mean age of participants at study entry was 64 years , 30 % of whom were female , 84 % had an entry diagnosis of stroke , and the remainder had an entry diagnosis of TIA alone . Mean baseline blood pressure was 147/86 mm Hg , with about half the patients reporting current drug treatment for hypertension . At r and omization , 58 % of patients were assigned to combination treatment with both study drugs versus placebos , and 42 % were assigned to perindopril alone versus placebo . CONCLUSIONS The successful completion of recruitment , together with current indicators of statistical power , suggest that PROGRESS should achieve its primary aim on schedule The beta blocker stroke ( " BEST " ) trial was design ed to see if the apparent protective effect of propranolol on cerebral function in patients with subarachnoid haemorrhage applied also to patients suffering from acute stroke . Three hundred and two conscious patients with clinical ly diagnosed hemispheric strokes sustained within the past 48 hours were r and omly assigned to receive atenolol , propranolol , or matching placebo capsules for three weeks . More early deaths occurred among the patients allocated to receive beta blockers , but this was largely explained by differences in the initial characteristics of the patients among the different treatment groups . By contrast , the outcome in a further 60 patients , who had been taking beta blockers at the time of their stroke but were otherwise similar to the patients in the trial , was considerably better , suggesting that prior treatment with beta blockers might be protective . The search for an effective medical treatment for acute stroke must continue . The approach used here , in which neurological outcome was assessed in a modest number of patients with a view to proceeding subsequently to a full scale trial of functional outcome , allows practical benefits of a treatment to be evaluated under realistic conditions and an ineffective treatment to be eliminated without undue cost The Multiple Risk Factor Intervention Trial was a r and omized primary prevention trial to test the effect of a multifactor intervention program on mortality from coronary heart disease ( CHD )  in 12,866 high-risk men aged 35 to 57 years . Men were r and omly assigned either to a special intervention ( SI ) program consisting of stepped-care treatment for hypertension , counseling for cigarette smoking , and dietary advice for lowering blood cholesterol levels , or to their usual sources of health care in the community ( UC ) . Over an average follow-up period of seven years , risk factor levels declined in both groups , but to a greater degree for the SI men . Mortality from CHD was 17.9 deaths per 1,000 in the SI group and 19.3 per 1,000 in the UC group , a statistically nonsignificant difference of 7.1 % ( 90 % confidence interval , -15 % to 25 ) . Total mortality rates were 41.2 per 1,000 ( SI ) and 40.4 per 1,000 ( UC ) . Three possible explanations for these findings are considered : ( 1 ) the overall intervention program , under these circumstances , does not affect CHD mortality ; ( 2 ) the intervention used does affect CHD mortality , but the benefit was not observed in this trial of seven years ' average duration , with lower-than-expected mortality and with considerable risk factor change in the UC group ; and ( 3 ) measures to reduce cigarette smoking and to lower blood cholesterol levels may have reduced CHD mortality within subgroups of the SI cohort , with a possibly unfavorable response to antihypertensive drug therapy in certain but not all hypertensive subjects . This last possibility was considered most likely , needs further investigation , and lends support to some preventive measures while requiring re assessment of others OBJECTIVE To assess the ability of antihypertensive drug treatment to reduce the risk of nonfatal and fatal ( total ) stroke in isolated systolic hypertension . DESIGN Multicenter , r and omized , double-blind , placebo-controlled . SETTING Community-based ambulatory population in tertiary care centers . PARTICIPANTS 4736 persons ( 1.06 % ) from 447,921 screenees aged 60 years and above were r and omized ( 2365 to active treatment , 2371 to placebo ) . Systolic blood pressure ranged from 160 to 219 mm Hg and diastolic blood pressure was less than 90 mm Hg . Of the participants , 3161 were not receiving antihypertensive medication at initial contact , and 1575 were . The average systolic blood pressure was 170 mm Hg ; average diastolic blood pressure , 77 mm Hg . The mean age was 72 years , 57 % were women , and 14 % were black . INTERVENTIONS -- Participants were stratified by clinical center and by antihypertensive medication status at initial contact . For step 1 of the trial , dose 1 was chlorthalidone , 12.5 mg/d , or matching placebo ; dose 2 was 25 mg/d . For step 2 , dose 1 was atenolol , 25 mg/d , or matching placebo ; dose 2 was 50 mg/d . MAIN OUTCOME MEASURES Primary . Nonfatal and fatal ( total ) stroke . Secondary . Cardiovascular and coronary morbidity and mortality , all-cause mortality , and quality of life measures . RESULTS Average follow-up was 4.5 years . The 5-year average systolic blood pressure was 155 mm Hg for the placebo group and 143 mm Hg for the active treatment group , and the 5-year average diastolic blood pressure was 72 and 68 mm Hg , respectively . The 5-year incidence of total stroke was 5.2 per 100 participants for active treatment and 8.2 per 100 for placebo . The relative risk by proportional hazards regression analysis was 0.64 ( P = .0003 ) . For the secondary end point of clinical nonfatal myocardial infa rct ion plus coronary death , the relative risk was 0.73 . Major cardiovascular events were reduced ( relative risk , 0.68 ) . For deaths from all causes , the relative risk was 0.87 . CONCLUSION In persons aged 60 years and over with isolated systolic hypertension , antihypertensive stepped-care drug treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36 % , with 5-year absolute benefit of 30 events per 1000 participants . Major cardiovascular events were reduced , with 5-year absolute benefit of 55 events per 1000 The associations of  diastolic blood pressure ( DBP )  with  stroke  and with coronary heart disease ( CHD ) were investigated in nine major prospect i ve observational studies : total 420,000 individuals , 843 strokes , and 4856 CHD events , 6 - 25 ( mean 10 ) years of follow-up . The combined results demonstrate positive , continuous , and apparently independent associations , with no significant heterogeneity of effect among different studies . Within the range of DBP studied ( about 70 - 110 mm Hg ) , there was no evidence of any " threshold " below which lower levels of DBP were not associated with lower risks of stroke and of CHD . Previous analyses have described the uncorrected associations of DBP measured just at " baseline " with subsequent disease rates . But , because of the diluting effects of r and om fluctuations in DBP , these substantially underestimate the true associations of the usual DBP ( ie , an individual 's long-term average DBP ) with disease . After correction for this " regression dilution " bias , prolonged differences in usual DBP of 5 , 7.5 , and 10 mm Hg were respectively associated with at least 34 % , 46 % , and 56 % less stroke and at least 21 % , 29 % , and 37 % less CHD . These associations are about 60 % greater than in previous uncorrected analyses . ( This regression dilution bias is quite general , so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths . ) The DBP results suggest that for the large majority of individuals , whether conventionally " hypertensive " or " normotensive " , a lower blood pressure should eventually confer a lower risk of vascular disease 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 There is widespread clinical uncertainty about lowering blood pressure in patients with ischaemic cerebrovascular disease . This often manifests as comparatively high thresholds for starting treatment and modest targets in reducing blood pressure . Concern has arisen partly from reports of a J shaped association between blood pressure and recurrent stroke in these patients .1 This relation may , however , be because severe strokes are associated both with a fall in blood pressure2 and independently with a relatively high risk of stroke recurrence , rather than from any adverse effects of low blood pressure itself . If this were true , then people with a history of minor cerebrovascular disease would have direct and continuous relations between usual blood pressure and risk of stroke , as observed in people without cerebrovascular disease.3 Data from To evaluate the effects of antihypertensive agents on the circadian blood pressure ( BP )  of patients with previous brain infa rct ion , the ambulatory BP was measured non-invasively for 24 h before and after administration of antihypertensive agents . One hundred milligrams of acebutolol twice daily ( n = 15 ) is effective in lowering the BP during the daytime , but has little effect during the night and the morning . Twenty milligrams of slow-release nifedipine twice daily ( n = 14 ) produced a consistent reduction in the BP over the entire 24-h period and effectively blunted the rise in BP in the morning . Captopril ( 12.5 mg ) twice daily ( n = 15 ) produced a mild reduction in BP with little change in the circadian pattern . The slow-release nifedipine group had the greatest decrease in mean systolic and diastolic BP . The heart rate significantly increased after administration of slow-release nifedipine and decreased after administration of acebutolol . To reduce stroke recurrence , we should consider the effects of antihypertensive agents on circadian BP in hypertensive patients with previous brain infa rct ion Summary The latter was due to a reduction in cardiac mortality ( −38 % , p=0.036 ) and a nonsignificant decrease in cerebrovascular mortality ( −32 % , p=0.16 ) . In the double-blind part of the trial , the total mortality rate was not significantly reduced ( −26 % , p=0.077 ) . However , cardiovascular mortality was reduced in the actively treated group ( −38 % , p=0.023 ) , owing to a reduction in cardiac deaths ( −47 % , p=0.048 ) and a non-significant decrease in cerebrovascular mortality ( −43 % , p=0.15 ) . Deaths from myocardial infa rct ion were reduced ( −60 % , p=0.043 ) , and study -terminating morbid cardiovascular events were significantly reduced by active treatment ( −60 % , p=0.0064 ) . Non-terminating cerebrovascular events were reduced ( −52 % , p=0.026 ) , but the non-terminating cardiac events were not ( + 3 % , p=0.98 ) . In the patients r and omised to active treatment there were 29 fewer cardiovascular events and 14 fewer cardiovascular deaths per 1000 patient years during the double-blind part of the trial . A double-blind r and omised placebo-controlled trial of antihypertensive treatment was conducted in patients over the age of 60 . Entry criteria included both a sitting diastolic blood pressure on placebo treatment in the range 90 to 119 mm Hg and a systolic pressure in the range 160 to 239 mm Eg . 840 patients were r and omised either to active treatment ( hydrochlorothiazide and triamterene ) or to  matching placebo  . If the blood pressure remained raised , methyldopa was added to the active regimen and matching placebo in the placebo group . An overall intention-to-treat analysis , combining the double-blind part of the trial and all subsequent follow-up , revealed a non-significant change in total mortality rate ( −9 % , p=0.41 ) but a significant reduction in cardiovascular mortality rate ( −27 % , p=0.037 )
target: Heterogeneity was present for several outcomes and was partly related to the class of antihypertensive drugs used ; angiotensin-converting enzyme inhibitors and diuretics separately , and especially together , reduced vascular events , while beta-receptor antagonists had no discernable effect .
  Evidence from r and omized controlled trials supports the use of antihypertensive agents in lowering blood pressure for the prevention of vascular events in patients with previous stroke or transient ischemic attack .
  Vascular prevention is associated positively with the magnitude by which blood pressure is reduced
background: BACKGROUND High blood pressure is a risk factor for stroke recurrence .
  We assessed the effectiveness of lowering blood pressure in preventing recurrent vascular events in patients with previous stroke or transient ischemic attack .