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 — Early after  coronary artery bypass surgery ( CABG ) , activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors . Methods and Results — The Ischemia Management with Accupril post – bypass Graft via Inhibition of the coNverting Enzyme ( IMAGINE ) trial tested whether early initiation ( ≤7 days ) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction ≥40 % . The trial was a double-blind , placebo-controlled study of 2553 patients r and omly assigned to quinapril , target dose 40 mg/d , or placebo , who were followed up to a maximum of 43 months . The mean ( SD ) age was 61 ( 10 ) years . The incidence of the primary composite end point ( cardiovascular death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary revascularization , unstable angina or heart failure requiring hospitalization , documented angina , and stroke ) was 13.7 % in the quinapril group and 12.2 % in the placebo group ( hazard ratio 1.15 , 95 % confidence interval 0.92 to 1.42 , P=0.212 ) over a median follow-up of 2.95 years . The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group ( hazard ratio 1.52 , 95 % confidence interval 1.03 to 2.26 , P=0.0356 ) . Adverse events also increased in the quinapril group , particularly during the first 3 months after CABG . Conclusions — In patients at low risk of cardiovascular events after CABG , routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG ; however , it increases the incidence of adverse events , particularly early after CABG . Thus , early after CABG , initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk BACKGROUND Calcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial . We aim ed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris . METHODS We r and omly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS  ( gastrointestinal therapeutic system ) 60 mg once daily and 3840 to placebo . The primary endpoint was the combination of death , acute myocardial infa rct ion , refractory angina , new overt heart failure , debilitating stroke , and peripheral revascularisation . Mean follow-up was 4.9 years ( SD 1.1 ) . Analysis was by intention to treat . FINDINGS 310 patients allocated nifedipine  died ( 1.64 per 100 patient-years ) compared with 291 people allocated placebo  ( 1.53 per 100 patient-years ; hazard ratio 1.07 [ 95 % CI 0.91 - 1.25 ] , p=0.41 ) . Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo ( 0.97 [ 0.88 - 1.07 ] , p=0.54 ) . With nifedipine , rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo ( 0.89 [ 0.83 - 0.95 ] , p=0.0012 ) . The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine , despite an increase in peripheral revascularisation . Nifedipine had no effect on the rate of myocardial infa rct ion . INTERPRETATION Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival .  Nifedipine GITS is safe and reduces the need for coronary angiography and interventions OBJECTIVES The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme ( ACE ) inhibitor , ramipril , on carotid atherosclerosis in patients with coronary , cerebrovascular or peripheral vascular disease . BACKGROUND Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models . It has been hypothesized that the clinical benefits of ACE inhibitors may , therefore , be mediated by effects on atherosclerosis . METHODS Six hundred seventeen patients were r and omized in equal proportions to ramipril ( 5 - 10 mg daily ) or placebo . At baseline , two years and four years , carotid atherosclerosis was assessed by B-mode ultrasound , and left ventricular mass was assessed by M-mode echocardiography . RESULTS Blood pressure ( BP ) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group ( p<0.001 ) . There was no difference between groups in the changes in common carotid artery wall thickness ( p = 0.58 ) or in carotid plaque ( p = 0.93 ) . Left ventricular mass index decreased by 3.8 g/m2 ( 4 % ) in the ramipril group compared with the placebo group ( 2p = 0.04 ) . CONCLUSIONS The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events . It is more likely that the benefits are due to lower BP , reduced left ventricular mass or other factors such as reversal of endothelial dysfunction BACKGROUND Our underst and ing of the growing population of very old patients ( aged > or=80 years ) with coronary artery disease and hypertension is limited , particularly the relationship between blood pressure and adverse outcomes . METHODS This was a secondary analysis of the INternational VErapamil SR-Tr and olapril STudy ( INVEST ) , which involved 22,576 clinical ly stable hypertensive coronary artery disease patients aged > or=50 years . The patients were grouped by age in 10-year increments ( aged > or=80 , n=2180 ; 70-<80 , n=6126 ; 60-<70 , n=7602 ; < 60 , n=6668 ) . Patients were r and omized to either verapamil SR- or atenolol-based treatment strategies , and primary outcome was first occurrence of all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS At baseline , increasing age was associated with higher systolic blood pressure , lower diastolic blood pressure , and wider pulse pressure ( P < .001 ) . Treatment decreased systolic , diastolic , and pulse pressure for each age group . However , the very old retained the widest pulse pressure and the highest proportion ( 23.6 % ) with primary outcome . The adjusted hazard ratio for primary outcomes showed a J-shaped relationship among each age group with on-treatment systolic and diastolic pressures . The systolic pressure at the hazard ratio nadir increased with increasing age , highest for the very old ( 140 mm Hg ) . However , diastolic pressure at the hazard ratio nadir was only somewhat lower for the very old ( 70 mm Hg ) . Results were independent of treatment strategy . CONCLUSION Optimal management of hypertension in very old coronary artery disease patients may involve targeting specific systolic and diastolic blood pressures that are higher and somewhat lower , respectively , compared with other age groups BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events . We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure . METHODS We recruited patients from October , 1997 , to June , 2000 . 13655 patients were registered with previous myocardial infa rct ion ( 64 % ) , angiographic evidence of coronary artery disease ( 61 % ) , coronary revascularisation ( 55 % ) , or a positive stress test only ( 5 % ) . After a run-in period of 4 weeks , in which all patients received perindopril , 12218 patients were r and omly assigned perindopril 8 mg once daily ( n=6110 ) , or matching placebo ( n=6108 ) . The mean follow-up was 4.2 years , and the primary endpoint was cardiovascular death , myocardial infa rct ion , or cardiac arrest . Analysis was by intention to treat . FINDINGS Mean age of patients was 60 years ( SD 9 ) , 85 % were male , 92 % were taking platelet inhibitors , 62 % beta blockers , and 58 % lipid-lowering therapy . 603 ( 10 % ) placebo and 488 ( 8 % ) perindopril patients experienced the primary endpoint , which yields a 20 % relative risk reduction ( 95 % CI 9 - 29 , p=0.0003 ) with perindopril . These benefits were consistent in all predefined subgroups and secondary endpoints . Perindopril was well tolerated . INTERPRETATION Among patients with stable coronary heart disease without apparent heart failure , perindopril can significantly improve outcome . About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event . Treatment with perindopril , on top of other preventive medications , should be considered in all patients with coronary heart 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 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 Tri 
    Output:
    
agent
These results suggest that reducing DBP to 80 mmHg or less would significantly reduce coronary revascularization and heart failure but at the expense of causing hypotension in CAD patients .
***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 — Early after  coronary artery bypass surgery ( CABG ) , activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors . Methods and Results — The Ischemia Management with Accupril post – bypass Graft via Inhibition of the coNverting Enzyme ( IMAGINE ) trial tested whether early initiation ( ≤7 days ) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction ≥40 % . The trial was a double-blind , placebo-controlled study of 2553 patients r and omly assigned to quinapril , target dose 40 mg/d , or placebo , who were followed up to a maximum of 43 months . The mean ( SD ) age was 61 ( 10 ) years . The incidence of the primary composite end point ( cardiovascular death , resuscitated cardiac arrest , nonfatal myocardial infa rct ion , coronary revascularization , unstable angina or heart failure requiring hospitalization , documented angina , and stroke ) was 13.7 % in the quinapril group and 12.2 % in the placebo group ( hazard ratio 1.15 , 95 % confidence interval 0.92 to 1.42 , P=0.212 ) over a median follow-up of 2.95 years . The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group ( hazard ratio 1.52 , 95 % confidence interval 1.03 to 2.26 , P=0.0356 ) . Adverse events also increased in the quinapril group , particularly during the first 3 months after CABG . Conclusions — In patients at low risk of cardiovascular events after CABG , routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG ; however , it increases the incidence of adverse events , particularly early after CABG . Thus , early after CABG , initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk BACKGROUND Calcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial . We aim ed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris . METHODS We r and omly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS  ( gastrointestinal therapeutic system ) 60 mg once daily and 3840 to placebo . The primary endpoint was the combination of death , acute myocardial infa rct ion , refractory angina , new overt heart failure , debilitating stroke , and peripheral revascularisation . Mean follow-up was 4.9 years ( SD 1.1 ) . Analysis was by intention to treat . FINDINGS 310 patients allocated nifedipine  died ( 1.64 per 100 patient-years ) compared with 291 people allocated placebo  ( 1.53 per 100 patient-years ; hazard ratio 1.07 [ 95 % CI 0.91 - 1.25 ] , p=0.41 ) . Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo ( 0.97 [ 0.88 - 1.07 ] , p=0.54 ) . With nifedipine , rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo ( 0.89 [ 0.83 - 0.95 ] , p=0.0012 ) . The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine , despite an increase in peripheral revascularisation . Nifedipine had no effect on the rate of myocardial infa rct ion . INTERPRETATION Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival .  Nifedipine GITS is safe and reduces the need for coronary angiography and interventions OBJECTIVES The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme ( ACE ) inhibitor , ramipril , on carotid atherosclerosis in patients with coronary , cerebrovascular or peripheral vascular disease . BACKGROUND Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models . It has been hypothesized that the clinical benefits of ACE inhibitors may , therefore , be mediated by effects on atherosclerosis . METHODS Six hundred seventeen patients were r and omized in equal proportions to ramipril ( 5 - 10 mg daily ) or placebo . At baseline , two years and four years , carotid atherosclerosis was assessed by B-mode ultrasound , and left ventricular mass was assessed by M-mode echocardiography . RESULTS Blood pressure ( BP ) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group ( p<0.001 ) . There was no difference between groups in the changes in common carotid artery wall thickness ( p = 0.58 ) or in carotid plaque ( p = 0.93 ) . Left ventricular mass index decreased by 3.8 g/m2 ( 4 % ) in the ramipril group compared with the placebo group ( 2p = 0.04 ) . CONCLUSIONS The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events . It is more likely that the benefits are due to lower BP , reduced left ventricular mass or other factors such as reversal of endothelial dysfunction BACKGROUND Our underst and ing of the growing population of very old patients ( aged > or=80 years ) with coronary artery disease and hypertension is limited , particularly the relationship between blood pressure and adverse outcomes . METHODS This was a secondary analysis of the INternational VErapamil SR-Tr and olapril STudy ( INVEST ) , which involved 22,576 clinical ly stable hypertensive coronary artery disease patients aged > or=50 years . The patients were grouped by age in 10-year increments ( aged > or=80 , n=2180 ; 70-<80 , n=6126 ; 60-<70 , n=7602 ; < 60 , n=6668 ) . Patients were r and omized to either verapamil SR- or atenolol-based treatment strategies , and primary outcome was first occurrence of all-cause death , nonfatal myocardial infa rct ion , or nonfatal stroke . RESULTS At baseline , increasing age was associated with higher systolic blood pressure , lower diastolic blood pressure , and wider pulse pressure ( P < .001 ) . Treatment decreased systolic , diastolic , and pulse pressure for each age group . However , the very old retained the widest pulse pressure and the highest proportion ( 23.6 % ) with primary outcome . The adjusted hazard ratio for primary outcomes showed a J-shaped relationship among each age group with on-treatment systolic and diastolic pressures . The systolic pressure at the hazard ratio nadir increased with increasing age , highest for the very old ( 140 mm Hg ) . However , diastolic pressure at the hazard ratio nadir was only somewhat lower for the very old ( 70 mm Hg ) . Results were independent of treatment strategy . CONCLUSION Optimal management of hypertension in very old coronary artery disease patients may involve targeting specific systolic and diastolic blood pressures that are higher and somewhat lower , respectively , compared with other age groups BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events . We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure . METHODS We recruited patients from October , 1997 , to June , 2000 . 13655 patients were registered with previous myocardial infa rct ion ( 64 % ) , angiographic evidence of coronary artery disease ( 61 % ) , coronary revascularisation ( 55 % ) , or a positive stress test only ( 5 % ) . After a run-in period of 4 weeks , in which all patients received perindopril , 12218 patients were r and omly assigned perindopril 8 mg once daily ( n=6110 ) , or matching placebo ( n=6108 ) . The mean follow-up was 4.2 years , and the primary endpoint was cardiovascular death , myocardial infa rct ion , or cardiac arrest . Analysis was by intention to treat . FINDINGS Mean age of patients was 60 years ( SD 9 ) , 85 % were male , 92 % were taking platelet inhibitors , 62 % beta blockers , and 58 % lipid-lowering therapy . 603 ( 10 % ) placebo and 488 ( 8 % ) perindopril patients experienced the primary endpoint , which yields a 20 % relative risk reduction ( 95 % CI 9 - 29 , p=0.0003 ) with perindopril . These benefits were consistent in all predefined subgroups and secondary endpoints . Perindopril was well tolerated . INTERPRETATION Among patients with stable coronary heart disease without apparent heart failure , perindopril can significantly improve outcome . About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event . Treatment with perindopril , on top of other preventive medications , should be considered in all patients with coronary heart 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 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 Tri 
    Output:
    