Summary
Survival after acute myocardial infarction has been enhanced
by treatment with thrombolytic agents, aspirin, and
&bgr;-adrenoceptor blockade. However, there remains a
substantial subgroup of patients who manifest clinical
evidence of heart failure despite the first two of these
treatments, and for whom &bgr;-adrenoceptor antagonists are
relatively or absolutely contraindicated. These patients have a
greatly increased risk of fatal and non-fatal ischaemic,
arrhythmic, and haemodynamic events. In this selected
high-risk subset of patients we investigated the effect of
therapy with the angiotensin converting enzyme (ACE) inhibitor
ramipril, postulating that it would lengthen survival.
2006 patients who had shown clinical evidence of heart
failure at any time after an acute myocardial infarction (AMI)
were recruited from 144 centres in 14 countries. Patients were
randomly allocated to double-blind treatment 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 considered the use of an ACE inhibitor to be
mandatory, were excluded. Follow-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
significantly lower for patients randomised to receive ramipril
(170 deaths; 17%) than for those randomised to receive
placebo (222 deaths; 23%). The observed risk reduction was
27% (95% Cl 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
individual patient)—namely, death, severe/resistant heart
failure, myocardial infarction, or stroke (95% CI 5% to 31%;
p=0·008).
Oral administration of ramipril to patients with clinical
evidence of either transient or ongoing heart failure, initiated
between the second and ninth day after myocardial infarction,
resulted in a substantial reduction in premature death from all
causes. This benefit was apparent as early as 30 days and was
consistent across a range of subgroups.