human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 8 
    Output:
    
agent
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
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 8 
    Output:
    