title: The ACCESS Study: Evaluation of Acute Candesartan Cilexetil Therapy in Stroke Survivors Nicardipine in the prevention of cerebral infarction. Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention: Principal Results of a Prospective Randomized Controlled Study (MOSES) Use of ramipril in preventing stroke: double blind randomised trial Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack Outcomes in subgroups of hypertensive patients treated with regimens based on valsartan and amlodipine: an analysis of findings from the VALUE trial Telmisartan to prevent recurrent stroke and cardiovascular events. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Influence of Nicardipine in Patients with High Risk of Stroke Post-stroke antihypertensive treatment study. A preliminary result. Blood pressure, stroke, and coronary heart disease: Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias Angiotensin-converting-enzyme inhibition in stable coronary artery disease. Blood pressure and risk of stroke in patients with cerebrovascular disease Trial of Secondary Prevention With Atenolol After Transient Ischemic Attack or Nondisabling Ischemic Stroke The Study on COgnition and Prognosis in the Elderly (SCOPE) – Major CV events and stroke in subgroups of patients
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 Two hundred and sixty-four patients were included in an open , r and omized , multicenter trial , with the aim of determining whether nicardipine can be useful in the prevention of  cerebral infa rct ion . The patients had experienced one or more transient ischemic attacks , reversible ischemic neurologic defect , or stroke with minor permanent neurological deficit in the 12 months before enrolling in the study . Each patient was r and omly assigned to received 250 mg of aspirin once daily plus 20 mg of nicardipine thrice daily ( n = 170 ) or 250 mg of aspirin once daily ( n = 94 ) for 12 months . During the 12-month treatment period , 12 % of the aspirin-plus-nicardipine group and 19 % of the aspirin-only group experienced an ischemic cerebrovascular event ; at six months , the cumulative incidence of events was significantly lower in the aspirin-plus-nicardipine group than in the aspirin-only group . One patient in each group died of a recurrent stroke .  Aspirin-related side effects were dyspepsia ( reported by four patients ) , heartburn ( by seven ) , nausea and vomiting ( by four ) , and melena ( by five ) ; nicardipine-related side effects were transient hypotension ( by two ) , headache ( by four ) , ankle edema ( by three ) , and constipation ( by four ) . Results indicate that the addition of nicardipine to antiplatelet treatment may safely prevent the recurrence of ischemic cerebrovascular events Background and Purpose — In hypertensive stroke patients , for the same level of blood pressure control , eprosartan will be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality . Methods — A total of 1405 well-defined , high-risk hypertensives with cerebral event during the last 24 months ( proven by cerebral computed tomography scan or nuclear magnetic resonance ) were r and omized to eprosartan or nitrendipine ( mean follow-up 2.5 years ) . Primary end point was the composite of total mortality and all cardiovascular and cerebrovascular events , including all recurrent events . Results — R and omization was successful without significant differences in the baseline characteristics . Blood pressure was reduced to a comparable extent without any significant differences between the 2 groups during the whole study period ( 150.7/84 mm Hg and 152.0/87.2 mm Hg with eprosartan and nitrendipine therapy to 137.5/80.8 mm Hg and 136.0/80.2 mm Hg , respectively , confirmed by ambulatory blood pressure monitoring ) . Moreover , already after 3 months , normotensive mean values were achieved , and 75.5 % reached values < 140/90 mm Hg with the eprosartan regimen and 77.7 % with the nitrendipine regimen . During follow-up , in total , 461 primary events occurred : 206 eprosartan and 255 nitrendipine ( incidence density ratio [ IDR ] , 0.79 ; 95 % CI , 0.66 to 0.96 ; P=0.014 ) . Cardiovascular events were : 77 eprosartan and 101 nitrendipine ( IDR , 0.75 ; 95 % CI , 0.55 to 1.02 ; P=0.06 ) ; cerebrovascular events : 102 eprosartan and 134 nitrendipine ( IDR , 0.75 ; 95 % CI , 0.58 to 0.97 ; P=0.03 ) . Conclusions — The Morbidity and Mortality After Stroke , Eprosartan Compared With Nitrendipine for Secondary Prevention ( MOSES ) study was the first to compare an angiotensin II type 1 receptor antagonist with a calcium antagonist in secondary stroke prevention . In these high-risk hypertensive stroke patients , an early normotensive and comparable blood pressure was achieved . The combined primary end point was significantly lower in the eprosartan group Abstract Objective : To determine the effect of the angiotensin converting enzyme inhibitor ramipril on the secondary prevention of stroke . Design : R and omised controlled trial with 2 × 2 factorial design . Setting : 267 hospitals in 19 countries . Participants : 9297 patients with vascular disease or diabetes plus an additional risk factor , followed for 4.5 years as part of the HOPE study . Outcome measures : Stroke ( confirmed by computed tomography or magnetic resonance imaging when available ) , transient ischaemic attack , and cognitive function . Blood pressure was recorded at entry to the study , after 2 years , and at the end of the study . Results : Reduction in blood pressure was modest ( 3.8 mm Hg systolic and 2.8 mm Hg diastolic ) . The relative risk of any stroke was reduced by 32 % ( 156 v 226 ) in the ramipril group compared with the placebo group , and the relative risk of fatal stroke was reduced by 61 % ( 17 v 44 ) . Benefits were consistent across baseline blood pressures , drugs used , and subgroups defined by the presence or absence of previous stroke , coronary artery disease , peripheral arterial disease , diabetes , or hypertension . Significantly fewer patients on ramipril  had cognitive or functional impairment . Conclusion : Ramipril  reduces the incidence of stroke in patients at high risk , despite a modest reduction in blood pressure . What is already known on this topic Treatment with aspirin and lowering blood pressure reduce the incidence of stroke What this study adds Ramipril , an angiotensin converting enzyme inhibitor , reduces strokes in patients at high risk whose blood pressure is not elevated , despite only a modest lowering of blood pressure The benefits are observed even when patients receive aspirin and other blood pressure lowering 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 Background In the Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial the primary outcome ( cardiac morbidity and mortality ) did not differ between valsartan and amlodipine-based treatment groups , although systolic blood pressure ( SBP ) and diastolic blood pressure reductions were significantly more pronounced with amlodipine . Stroke incidence was non-significantly , and myocardial infa rct ion was significantly lower in the amlodipine-based regimen , whereas cardiac failure was non-significantly lower on valsartan . Objectives The study protocol specified additional analyses of the primary endpoint according to : sex ; age ; race ; geographical region ; smoking status ; type 2 diabetes ; total cholesterol ; left ventricular hypertrophy ; proteinuria ; serum creatinine ; a history of coronary heart disease ; a history of stroke or transient ischemic attack ; and a history of peripheral artery disease . Additional subgroups were isolated systolic hypertension and classes of antihypertensive agents used immediately before r and omization . Methods The 15 245 hypertensive patients participating in VALUE were divided into subgroups according to baseline characteristics . Treatment by subgroup interaction analyses were carried out by a Cox proportional hazard model . Within each subgroup , treatment effects were assessed by hazard ratios and 95 % confidence intervals . Results For cardiac mortality and morbidity , the only significant subgroup by treatment interaction was of sex ( P = 0.016 ) , with the hazard ratio indicating a relative excess of cardiac events with valsartan treatment in women but not in men , but SBP differences in favour of amlodipine were distinctly greater in women . No other subgroup showed a significant difference in the composite cardiac outcome between valsartan and amlodipine-based treatments . For secondary endpoints , a sex-related significant interaction was found for heart failure ( P < 0.0001 ) , with men but not women having a lower incidence of heart failure with valsartan . Conclusion As in the whole VALUE cohort , in no subgroup of patients were there differences in the incidence of the composite cardiac endpoint with valsartan and amlodipine-based treatments , despite a greater blood pressure decrease in the amlodipine group . The only exception was sex , in which the amlodipine-based regimen was more effective than valsartan in women , but not in men , whereas the valsartan regimen was more effective in preventing cardiac failure in men than in women BACKGROUND Prolonged lowering of blood pressure after a stroke reduces the risk of recurrent stroke . In addition , inhibition of the renin-angiotensin system in high-risk patients reduces the rate of subsequent cardiovascular events , including stroke . However , the effect of lowering of blood pressure with a renin-angiotensin system inhibitor soon after a stroke has not been clearly established . We evaluated the effects of therapy with an angiotensin-receptor blocker , telmisartan , initiated early after a stroke . METHODS In a multicenter trial involving 20,332 patients who recently had an ischemic stroke , we r and omly assigned 10,146 to receive telmisartan  ( 80 mg daily ) and 10,186 to receive  placebo . The primary outcome was recurrent stroke . Secondary outcomes were major cardiovascular events ( death from cardiovascular causes , recurrent stroke , myocardial infa rct ion , or new or worsening heart failure ) and new-onset diabetes . RESULTS The median interval from stroke to r and omization was 15 days . During a mean follow-up of 2.5 years , the mean blood pressure was 3.8/2.0 mm Hg lower in the telmisartan group than in the placebo group . A total of 880 patients ( 8.7 % ) in the telmisartan group and 934 patients ( 9.2 % ) in the placebo group had a subsequent stroke ( hazard ratio in the telmisartan group , 0.95 ; 95 % confidence interval [ CI ] , 0.86 to 1.04 ; P=0.23 ) . Major cardiovascular events occurred in 1367 patients ( 13.5 % ) in the telmisartan group and 1463 patients ( 14.4 % ) in the placebo group ( hazard ratio , 0.94 ; 95 % CI , 0.87 to 1.01 ; P=0.11 ) . New-onset diabetes occurred in 1.7 % of the telmisartan group and 2.1 % of the placebo group ( hazard ratio , 0.82 ; 95 % CI , 0.65 to 1.04 ; P=0.10 ) . CONCLUSIONS Therapy with telmisartan initiated soon after an ischemic stroke and continued for 2.5 years did not significantly lower the rate of recurrent stroke , major cardiovascular events , or diabetes . ( Clinical Trials.gov number , NCT00153062 . 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 Blood pressure and clinical status of 1,736 patients with cerebrovascular disease were observed during 12 months of treatment with nicardipine . The most common diagnoses were chronic cerebral ischemia ( 53.2 % ) , transient ischemic attacks ( TIA ; 25.1 % ) , and cerebral infa rct ( 8.7 % ) ; 50.1 % of patients were classed as hypertensive [ systolic blood pressure ( SBP ) ≥ 160 mm Hg or diastolic blood pressure ( DBP ) ≥ 90 mm Hg ] . Most patients ( 91.2 % ) received a daily dose of 60 mg nicardipine . Additional treatments included diuretics ( 37 % ) , β-blockers ( 11.5 % ) , other antihypertensive drugs ( 15.8 % ) , platelet antiaggregants ( 25.1 % ) , and cardiotonic drugs ( 15.1 % ) . A total of 282 patients ( 16.2 % ) were lost to follow-up , 21 ( 1.2 % ) patients withdrew due to side effects , 32 ( 1.8 % ) died , and 9 ( 0.5 % ) patients had treatment interrupted due to concomitant illness . In the hypertensive subgroup , blood pressure ( SBP/ DBP ) was reduced from a mean baseline value of 175 ± 22/97 ± 14 mm Hg to 152 ± 17/85 ± 11 mm Hg at 3 months and 149 ± 23/81 ± 11 mm Hg after 12 months of treatment . The incidence of TIA or stroke among these patients was reduced from 29 cases ( 3.5 % ) during the first 3 months to 11 cases ( 1.54 % ) during months 4–12 ( p < 0.01 ) . In normotensive patients there were 18 ( 2.15 % ) cases during months 1–3 and 13 ( 1.55 % ) cases during months 4–12 ( difference not significant ) . In the 280 patients treated  with nicardipine alone , the most frequent side effects during the first month were facial flushing ( 6.8 % ) , gastrointestinal problems ( 5 % ) , dizziness ( 3.2 % ) , headache ( 3.2 % ) , drowsiness ( 3.2 % ) , and hypotension ( 1.1 % ) . Most of these side effects were transient . These results demonstrate that nicardipine lowered blood pressure over the 12 months of observation . This may have contributed to the reduction in the incidence of TIA or stroke among hypertensive patients during months 4–12 Post-stroke Antihypertensive Treatment Study ( PATS ) was a r and omized , double-blind and placebo-controlled trial , which aim ed at determining whether antihypertensive treatment could reduce the risk of fatal and nonfatal stroke incidence in patients with a history of stroke or transient ischemic attack ( TIA ) . 5,665 patients were r and omized by a sealed envelope system . Systolic blood pressure ( SBP ) ranged from 80 to 280 mm Hg and diastolic ( DBP ) from 50 to 150 mmHg . The average SBP was 154 mmHg and average DBP 93 mmHg . The mean age was 60 years . Among the patients , women accounted for 28 % . In 71 % the latest stroke was ischemic . Average follow-up approximated to 2 years . The three-year average SBP was 149 mmHg for the placebo group and 144 mmHg for the indapamide treatment group , and the three-year DBP was 89 mmHg and 87 mmHg respectively . The three-year first incidence of fatal and nonfatal stroke was 12.3 per 100 patients placebo treatment and 9.4 per 100 with indapamide . The relative risk by proportional hazards regression analysis was 0.71 ( P = 0.0009 ) . For deaths from all causes , the relative risk was 0.91 . ( P > 0.05 ) . The findings of this trial indicate that in patients with a history of stroke or TIA , blood pressure reduction of 5/2 mmHg with 2.5 mg indapamide reduced the first incidence of fatal and nonfatal stroke by 29 % , with three-year absolute benefit of 29 events per 1000 participants 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 BACKGROUND Angiotensin-converting-enzyme ( ACE ) inhibitors are effective in reducing the risk of heart failure , myocardial infa rct ion , and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure . ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure . METHODS In the Prevention of Events with Angiotensin Converting Enzyme Inhibition ( PEACE ) Trial , we tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from the addition of ACE inhibitors to modern conventional therapy . The trial was a double-blind , placebo-controlled study in which 8290 patients were r and omly assigned to receive either  tr and olapril  at a target dose of  4 mg  per  day ( 4158 patients ) or matching placebo ( 4132 patients ) . RESULTS The mean ( + /-SD ) age of the patients was 64+/-8 years , the mean blood pressure 133+/-17/78+/-10 mm Hg , and the mean left ventricular ejection fraction 58+/-9 percent . The patients received intensive treatment , with 72 percent having previously undergone coronary revascularization and 70 percent receiving lipid-lowering drugs . The incidence of the primary end point -- death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization -- was 21.9 percent in the tr and olapril group , as compared with 22.5 percent in the placebo group ( hazard ratio in the tr and olapril group , 0.96 ; 95 percent confidence interval , 0.88 to 1.06 ; P=0.43 ) over a median follow-up period of 4.8 years . CONCLUSIONS In patients with stable coronary heart disease and preserved left ventricular function who are receiving " current st and ard " therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease , there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes , myocardial infa rct ion , or coronary revascularization 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 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 The Study on COgnition and Prognosis in the Elderly ( SCOPE ) assessed the effect of c and esartan on cardiovascular outcomes in elderly patients with mild to moderate hypertension . Patients were r and omized to c and esartan 8–16 mg daily ( n = 2477 ) or placebo ( n = 2460 ) . Due to extensive add‐on therapy , blood pressure reduction was only about 3/2 mmHg greater in the c and esartan group than in the control group . Nevertheless , non‐fatal stroke was reduced by 28 % ( p = 0.04 ) in the c and esartan group compared to the control group , and there was a non‐significant 11 % reduction in major cardiovascular events ( p = 0.19 ) . This report provides results in pre‐specified subgroups of patients ( age , gender , diabetes , history of stroke , smoking and cardiovascular risk at r and omization ) . Reductions in major cardiovascular events and stroke  with c and esartan‐based therapy were indicated in all subgroups . A significant interaction between treatment and subgroups was found for one pair of subgroups only ; the reduction in major cardiovascular events with c and esartan  was greater in patients with a previous stroke ( 64 % reduction , p = 0.004 ) than in those without ( 5 % reduction , p>0.20 ) . In conclusion , this analysis indicates consistent favourable effects of c and esartan‐based  therapy on major cardiovascular events and stroke across the different subgroups of patients . However , the benefit was particularly pronounced in patients who entered the study with a previous stroke
target: CONCLUSION Despite recent large trials showing no significant effect , in patients that have experienced a TIA or stroke , blood pressure lowering agents reduced the occurrence of subsequent stroke and cardiovascular events .
  The rate of myocardial infa rct ion and all-cause mortality was unchanged
background: BACKGROUND While hypertension is a leading risk factor for an initial stroke , the role of blood pressure lowering to prevent subsequent stroke is less clear .
  The results of recent large clinical trials investigating effects of antihypertensive agents in patients with a history of stroke have not shown a significant benefit ; findings that are at odds with previous data .
  Our meta- analysis systematic ally evaluates the available , relevant trials to examine the role of antihypertensive drugs in preventing recurrent stroke .