EFFECT OF RAMIPRIL ON MORTALITY AND MORBIDITY OF SURVIVORS OF ACUTE MYOCARDIAL-INFARCTION WITH CLINICAL-EVIDENCE OF HEART-FAILURE

Survival after acute myocardial infarction has been enhanced by treatm ent with thrombolytic agents, aspirin, and beta-adrenoceptor blockade. However, there remains a substantial subgroup of patients who manifes t clinical evidence of heart failure despite the first two of these tr eatments, and for whom beta-adrenoceptor antagonists are relatively or absolutely contraindicated. These patients have a greatly increased r isk of fatal and non-fatal ischaemic, arrhythmic, and haemodynamic eve nts. In this selected high-risk subset of patients we investigated the effect of therapy with the angiotensin converting enzyme (ACE) inhibi tor ramipril, postulating that it would lengthen survival. 2006 patien ts who had shown clinical evidence of heart failure at any time after an acute myocardial infarction (AMI) were recruited from 144 centres i n 14 countries. Patients were randomly allocated to double-blind treat ment with either placebo (992 patients) or ramipril (1014 patients) on day 3 to day 10 after AMI (day 1). Patients with severe heart failure resistant to conventional therapy, in whom the attending physician co nsidered the use of an ACE inhibitor to be mandatory, were excluded. F ollow-up was continued for a minimum of 6 months and an average of 15 months. On intention-to-treat analysis mortality from all causes was s ignificantly lower for patients randomised to receive ramipril (170 de aths; 17%) than for those randomised to receive placebo (222 deaths; 2 3%). The observed risk reduction was 27% (95% CI 11% to 40%; p=0.002). Analysis of prespecified secondary outcomes revealed a risk reduction of 19% for the first validated outcome (ie, first event in an individ ual patient)-namely, death, severe/resistant heart failure, myocardial infarction, or stroke (95% CI 5% to 31%; p=0.008). Oral administratio n of ramipril to patients with clinical evidence of either transient o r ongoing heart failure, initiated between the second and ninth day af ter myocardial infarction, resulted in a substantial reduction in prem ature death from all causes. This benefit was apparent as early as 30 days and was consistent across a range of subgroups.