Elsevier

The Lancet

Volume 355, Issue 9215, 6 May 2000, Pages 1575-1581
The Lancet

Articles
Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: a systematic overview of data from individual patients

https://doi.org/10.1016/S0140-6736(00)02212-1Get rights and content

Summary

Background

We undertook a prospective systematic overview based on data from individual patients from five long-term randomised trials that assessed inhibitors of angiotensin-converting enzyme (ACE) in patients with left-ventricular dysfunction or heart failure.

Methods

Three of the trials enrolled patients within a week after acute myocardial infarction. Data were combined by use of the Peto-Yusuf method.

Findings

Overall 12 763 patients were randomly assigned treatment or placebo and followed up for an average of 35 months. In the three post-infarction trials (n=5966), mortality was lower with ACE inhibitors than with placebo (702/2995 [23·4%] vs 866/2971 [29·1%]; odds ratio 0·74 [95% Cl 0·66–0·83]), as were the rates of readmission for heart failure (355 [11·9%] vs 460 [15·5%]; 0·73 [0·63–0·85]), reinfarction (324 [10·8%] vs 391 [13·2%]; 0·80 [0·69-0·94]), or the composite of these events (1049 [35·0%] vs 1244 [41·9%]; 0·75 [0·67–0·83]; all p < 0·001). For all five trials the ACE-inhibitor group had lower rates of death than the placebo group (1467/6391 [23·0%] vs 1710/6372 [26·8%]; 0·80 [0·74–0·87]) and lower rates of reinfarction (571 [8·9%] vs 703 [11·0%]; 0·79 [0·70–0·89]), readmission for heart failure (876 [13-·%] vs 1202 [18·9%]; 0·67 [0·61–0·74]), and the composite of these events (2161 [33·8%] vs 2610 [41·0%]; 0·72 [0·67–0·78]; all p < 0·0001). The benefits were observed early after the start of therapy and persisted long term. The benefits of treatment on all outcomes were independent of age, sex, and baseline use of diuretics, aspirin, and β-blockers. Although there was a trend towards greater reduction in risk of death or readmission for heart failure in patients with lower ejection fractions, benefit was apparent over the range examined.

Interpretation

This systematic overview shows that ACE inhibitors lower rates of mortality, myocardial infarction, and hospital admission for heart failure in patients with left-ventricular dysfunction or heart failure with or without a recent myocardial infarct. The use of ACE inhibitors should be part of routine practice in these patients.

Introduction

Several large randomised trials have assessed the role of angiotensin-converting-enzyme (ACE) inhibitors for patients with acute myocardial infarction. Some trials started ACE inhibitors within 24–36 h of the onset of acute myocardial infarction in unselected patients and continued treatment for a few weeks or months (short-term trials).1 Other trials2, 3, 4 started treatment a few days or weeks after the onset of acute myocardial infarction in patients with heart failure or left-ventricular dysfunction, and continued treatment for at least a year (long-term trials). In addition, two trials of patients with low ejection fractions5, 6 included a substantial number of patients with previous myocardial infarction and randomly assigned them long-term therapy with an ACE inhibitor or placebo. Although each trial provides useful data on mortality and morbidity, many important questions remain unanswered. Uncertainty remains about the size of the treatment benefit on mortality, hospital admission for heart failure, and reinfarction; whether the benefits occur soon after randomisation and persist on long-term treatment; and whether the benefits of treatment vary in different subgroups of patients or those taking different medications concomitantly.

Systematic overviews (meta-analyses) of large randomised trials improve estimates of treatment effects because they have greater statistical power than the individual trials. Overviews that use data from individual patients can provide more information than those that use published collective data because they have greater flexibility in analysis. In particular, more reliable information on the estimated overall treatment effect size, the effects of treatments in subgroups of patients, the risk-benefit ratios in these patients, and the time course of the treatment effect can be obtained by use of data from individuals in each trial compared with a meta-analysis based on published data.

A systematic overview of the short-term ACE-inhibitor trials has been reported previously.1 We report a collaborative overview of the long-term trials, which sought to estimate more precisely the overall benefits (on deaths, admission for heart failure, and reinfarction) and risks of ACE inhibitors, and to assess treatment effects in clinically important subgroups.

Section snippets

Data collection

Experience from previous overviews has shown that most of the clinically useful information comes from the large randomised trials. Thus, this overview was prospectively limited to randomised trials of more than 1000 patients in which the intention was to treat patients with ACE inhibitors or control after myocardial infarction for at least 12 months and to examine their consistency with the SOLVD (Studies of Left Ventricular Dysfunction) trials.5 We carried out a literature search of

Patients

The three long-term, randomised double-blind placebo-controlled trials of total sample size greater than 1000 patients (table 1) were SAVE (Survival and Ventricular Enlargement), AIRE (Acute Infarction Ramipril Efficacy), and TRACE (trandolapril in patients with reduced left-ventricular function after acute myocardial infarction). A total of 5966 patients with evidence of left-ventricular dysfunction or clinical heart failure were randomly assigned ACE-inhibitor treatment or placebo control

Discussion

Overall there was a 28% reduction in death, myocardial infarction, and hospital admission for heart failure in patients with left-ventricular dysfunction after myocardial infarction treated with ACE inhibitors. The upper confidence limit indicated at least a 22% risk reduction. Given the high absolute risks among the patients included in these trials, this relative risk reduction translates into 70 patients with at least one event prevented for every 1000 patients treated.

These data complement

References (16)

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