***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 
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    Input: Cardiovascular events ( CVEs ) are the leading cause of death in chronic hemodialysis patients . Results of trials in non-end-stage renal disease ( ESRD ) patients can not be extrapolated to patients with ESRD . It is critical to test cardiovascular therapies in these high-risk patients who are usually excluded from major cardiovascular trials . The study objective was to evaluate the effect of fosinopril on CVEs in patients with ESRD . Eligible patients were r and omized to fosinopril 5 mg titrated to 20 mg daily ( n=196 ) or placebo ( n=201 ) plus conventional therapy for 24 months . The primary end point was combined fatal and nonfatal first major CVEs ( cardiovascular death , resuscitated death , nonfatal stroke , heart failure , myocardial infa rct ion , or revascularization ) . No significant benefit for fosinopril was observed in the intent to treat analysis ( n=397 ) after adjusting for independent predictors of CVEs ( RR=0.93 , 95 % confidence interval ( CI ) 0.68 - 1.26 , P=0.35 ) . The per protocol secondary supportive analysis ( n=380 ) found a trend towards benefit for fosinopril ( adjusted RR=0.79 ( 95 % CI 0.59 - 1.1 , P=0.099 ) ) . In the patients who were hypertensive at baseline , systolic and diastolic blood pressures were significantly decreased in the fosinopril as compared to the placebo group . After adjustment for risk factors , trends were observed suggesting fosinopril may be associated with a lower risk of CVEs . These trends may have become statistically significant had the sample size been larger , and these findings warrant further study Background — Patients with reduced renal function are at increased risk for adverse cardiovascular outcomes . In the post – myocardial infa rct ion setting , angiotensin-converting enzyme ( ACE ) inhibitors have been shown to be as effective in patients with impaired renal function as in those with preserved renal function . Methods and Results — We assessed the relation between renal function and outcomes , the influence of ACE inhibition on this relation , and whether renal function modifies the effectiveness of ACE inhibition in patients with stable coronary artery disease and preserved systolic function enrolled in the Prevention of Events with ACE inhibition trial ( PEACE ) . Patients ( n=8290 ) were r and omly assigned to receive tr and olapril ( target , 4 mg/d ) or placebo .  Clinical creatinine measures were available for 8280 patients before r and omization . The estimated glomerular filtration rate ( eGFR ) was calculated with the 4-point Modification of Diet in Renal Disease equation . Renal function was related to outcomes , and the influence of ACE-inhibitor therapy was assessed with formal interaction modeling . The mean eGFR in PEACE was 77.6±19.4 , and 1355 ( 16.3 % ) patients had reduced renal function ( eGFR < 60 mg · mL−1 · 1.73 m−2 ) . We observed a significant interaction between eGFR and treatment group with respect to cardiovascular and all-cause mortality ( P=0.02 ) . Tr and olapril was associated with a reduction in total mortality in patients with reduced renal function ( adjusted HR , 0.73 ; 95 % CI , 0.54 to 1.00 ) but not in patients with preserved renal function ( adjusted HR , 0.94 ; 95 % CI , 0.78 to 1.13 ) . Conclusions — Although tr and olapril did not improve survival in the overall PEACE cohort , in which mean eGFR was relatively high , tr and olapril reduced mortality in patients with reduced eGFR . These data suggest that reduced renal function may define a subset of patients most likely to benefit from ACE-inhibitor therapy for cardiovascular protection BACKGROUND Coprescription of aspirin and ACE inhibitors is frequent in heart failure caused by coronary artery disease . Negative interaction between aspirin and enalapril has been reported , presumably through inhibition by aspirin of ACE inhibitor-induced prostagl and in synthesis . Ticlopidine is a potent antiplatelet agent without interaction with prostagl and in synthesis . METHODS AND RESULTS The objective of this study was to compare the influence of a coadministration of ticlopidine or aspirin on the hemodynamic effects of an ACE inhibitor ( enalapril ) in patients with chronic heart failure . Twenty patients with severe heart failure were enrolled in a double-blind comparative trial and allocated to ticlopidine ( 500 mg daily , 12 patients ) or aspirin ( 325 mg daily , 8 patients ) . Hemodynamic evaluation was performed after 7 days of treatment , every hour for 4 hours after an oral administration of 10 mg of enalapril . Significant reductions in systemic vascular resistance were observed in the ticlopidine group , in contrast to no significant decrease in the aspirin group . A significant ( P=0.03 ) time-by-treatment interaction indicated significant aspirin-enalapril drug interaction . Total pulmonary resistance decreased significantly in both groups , with no difference between patients assigned to aspirin or ticlopidine . CONCLUSIONS Enalapril reduced systemic vascular resistance more effectively when given in combination with ticlopidine than with aspirin . In contrast , the reduction in total pulmonary resistance is similar when enalapril is administered in combination with aspirin or ticlopidine . Negative aspirin-enalapril interaction on prostagl and in synthesis presumably alters vasodilatation in systemic vessels , whereas prostagl and in-independent actions of ACE inhibition such as pulmonary arterial vasodilatation are maintained BACKGROUND Both hyper- and hypokalemia increase cardiovascular risk . Modest hyperkalemia is common with angiotensin-converting enzyme inhibition . We studied post-hoc the association of an initial , on-treatment serum potassium measurement with subsequent cardiovascular outcomes over 4.5 years in 9297 individuals at high cardiovascular risk , r and omized to an ACE inhibitor or to placebo .  METHODS Post-hoc analysis of cardiovascular outcomes , as related to serum potassium levels , in the HOPE ( Heart Outcomes and Prevention Evaluation ) study which compared ramipril to placebo , and included 692 patients with a serum potassium level > 5.0 mM and 137 with a serum potassium level < 3.5 mM , defined as hyper- and hypokalemia , respectively .  Serum potassium  was measured 1 month after start of r and omized treatment . RESULTS With hyperkalemia , the primary event rate was unchanged compared to normokalemia ( 15.5 vs 15.7 % , p > 0.4 , respectively ) , with hypokalemia , the primary event rate was higher ( 22.6 % vs 15.5 % , respectively , p = 0.023 ) . The hazard ratio for the primary outcome associated with this initial hypokalemia was 1.44 ( 1.00 - 2.06 ) on multivariate analysis . The combined primary outcome ( myocardial infa rct ion , cardiovascular death , stroke ) was not different throughout deciles of serum potassium but the lowest and highest deciles included many with normokalemia . R and omized treatment was withheld because of hyperkalemia in 8 and 6 people allocated to ramipril and placebo , respectively . The benefit of ramipril on cardiovascular outcomes was independent of serum potassium , but ramipril reduced hypokalemia in the entire cohort ( 1.15 vs 1.86 % with placebo , p = 0.005 ) , particularly in those participants on diuretics ( 3.8 % vs 6.5 % , p = 0.07 ) . CONCLUSIONS In patients at high cardiovascular risk , modest hypokalemia predicts a less favorable outcome while modest hyperkalemia does not . Ramipril reduces hypokalemia and decreases risk BACKGROUND Diabetes mellitus is a strong risk factor for cardiovascular and renal disease . We investigated whether the angiotensin-converting-enzyme ( ACE ) inhibitor ramipril can lower these risks in patients with diabetes . METHODS 3577 people with diabetes included in the Heart Outcomes Prevention Evaluation study , aged 55 years or older , who had a previous cardiovascular event or at least one other cardiovascular risk factor , no clinical proteinuria , heart failure , or low ejection fraction , and who were not taking ACE inhibitors , were r and omly assigned ramipril ( 10 mg/day ) or placebo , and vitamin E or placebo , according to a two-by-two factorial design . The combined primary outcome was myocardial infa rct ion , stroke , or cardiovascular death . Overt nephropathy was a main outcome in a sub study . FINDINGS The study was stopped 6 months early ( after 4.5 years ) by the independent data safety and monitoring board because of a consistent benefit of ramipril compared with placebo . Ramipril lowered the risk of the combined primary outcome by 25 % ( 95 % CI 12 - 36 , p=0.0004 ) , myocardial infa rct ion by 22 % ( 6 - 36 ) , stroke by 33 % ( 10 - 50 ) , cardiovascular death by 37 % ( 21 - 51 ) , total mortality by 24 % ( 8 - 37 ) , revascularisation by 17 % ( 2 - 30 ) , and overt nephropathy by 24 % ( 3 - 40 , p=0.027 ) . After adjustment for the changes in systolic ( 2.4 mm Hg ) and diastolic ( 1.0 mm Hg ) blood pressures , ramipril still lowered the risk of the combined primary outcome by 25 % ( 12 - 36 , p=0.0004 ) . INTERPRETATION Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes . The cardiovascular benefit was greater than that attributable to the decrease in blood pressure . This treatment represents a vasculoprotective and renoprotective effect for people with diabetes BACKGROUND Treatment with angiotensin-converting-enzyme ( ACE ) inhibitors reduces mortality among survivors of acute myocardial infa rct ion , but whether to use ACE inhibitors in all patients or only in selected patients is uncertain . METHODS We screened 6676 consecutive patients with 7001 myocardial infa rct ions confirmed by enzyme studies . A total of 2606 patients had echocardiographic evidence of left ventricular systolic dysfunction ( ejection fraction , < or = 35 percent ) . On days 3 to 7 after infa rct ion , 1749 patients were r and omly assigned to receive oral tr and olapril ( 876 patients ) or placebo ( 873 patients ) . The duration of follow-up was 24 to 50 months . RESULTS During the study period , 304 patients ( 34.7 percent ) in the tr and olapril group died , as compared with 369 ( 42.3 percent ) in the placebo group ( P = 0.001 ) . The relative risk of death in the tr and olapril group , as compared with the placebo group , was 0.78 ( 95 percent confidence interval , 0.67 to 0.91 ) . Tr and olapril also reduced the risk of death from cardiovascular causes ( relative risk , 0.75 ; 95 percent confidence interval , 0.63 to 0.89 ; P = 0.001 ) and sudden death ( relative risk , 0.76 ; 95 percent confidence interval , 0.59 to 0.98 ; P = 0.03 ) . Progression to severe heart failure was less frequent in the tr and olapril group ( relative risk , 0.71 ; 95 percent confidence interval , 0.56 to 0.89 ; P = 0.003 ) . In contrast , the risk of recurrent myocardial infa rct ion ( fatal or nonfatal ) was not significantly reduced ( relative risk , 0.86 ; 95 percent confidence interval , 0.66 to 1.13 ; P = 0.29 ) . CONCLUSIONS Long-term treatment with tr and olapril in patients with reduced left ventricular function soon after myocardial infa rct ion significantly reduced the risk of overall mortality , mortality from cardiovascular causes , sudden death , and the development of severe heart failure . That mortality was reduced in a r and omized study enrolling 25 percent of consecutive patients screened should encourage the selective use of ACE inhibition after myocardial infa rct ion AIMS Cardiovascular ( CV ) disease is the leading cause of death in the elderly . The use of ACE-inhibitors in elderly patients with chronic stable vascular disease has not been previously reported . METHODS AND RESULTS The HOPE trial evaluated the effects of ramipril and vitamin E in high-risk vascular disease patients . We report the effects of ramipril in the elderly HOPE study patients , defined as those > or = 70 years of age . A total of 2755 elderly patients with vascular disease or diabetes and at least one additional CV risk factor and without heart failure 
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Contribution Authors of this systematic review concluded that ACE inhibitors reduce risk for mortality , stroke , and myocardial infa rct ion in patients with stable ischemic heart disease and preserved left ventricular function who already receive st and ard treatments , such as -blockers , statins , and aspirin .