Elsevier

The Lancet

Volume 361, Issue 9372, 31 May 2003, Pages 1843-1848
The Lancet

Articles
Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study

https://doi.org/10.1016/S0140-6736(03)13501-5Get rights and content

Summary

Background

In the studies of left ventricular dysfunction (SOLVD), enalapril reduced mortality in patients with symptomatic but not asymptomatic left ventricular systolic dysfunction during the trial. We did a 12-year follow-up of SOLVD to establish if the mortality reduction with enalapril among patients with heart failure was sustained, and whether a subsequent reduction in mortality would emerge among those with asymptomatic ventricular dysfunction.

Methods

Of the 6797 patients previously enrolled in the SOLVD prevention and treatment trials, we ascertained the subsequent vital status of 5165 individuals who were alive when the trials had been completed. Follow-up was done through direct contacts in Belgium and linkages with national death registries and federal beneficiary or historic tax summary files in the USA and Canada.

Findings

Follow-up was 99·8% (6784/6797) complete. In the prevention trial, 50·9% (1074/2111) of the enalapril group had died compared with 56·4% (1195/2117) of the placebo group (generalised Wilcoxon p=0·001). In the treatment trial, 79·8% (1025/1285) of the enalapril group had died compared with 80·8% (1038/1284) of the placebo group (generalised Wilcoxon p=0·01). The reductions in cardiac deaths were significant and similar in both trials. When data for the prevention and treatment trials were combined, the hazard ratio for death was 0·90 for the enalapril group compared with the placebo group (95% CI 0·84–0·95, generalised Wilcoxon p=0·0003). Enalapril extended median survival by 9·4 months in the combined trials (95% CI 2·8–16·5, p=0·004).

Interpretation

Treatment with enalapril for 3–4 years led to a sustained improvement in survival beyond the original trial period in patients with left ventricular systolic dysfunction, with an important increase in life expectancy.

Introduction

the end of scheduled follow-up of the studies of left ventricular dysfunction (SOLVD), treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril improved survival in patients with heart failure and left ventricular dysfunction, whereas in patients who were asymptomatic and had left ventricular dysfunction, no clear reduction in mortality was seen.1, 2 However, the risks of heart failure and myocardial infarction were reduced in the enalapril group,1, 3 suggesting that the reductions in morbidity seen in the trial could translate into improvements in long-term survival after the trial. Therefore, the extended studies of left ventricular dysfunction (X-SOLVD) followed up patients for an additional 9 years to assess the effect of enalapril on their long-term survival and life expectancy. We present 12-year follow-up data of all 6797 patients who were previously enrolled in the SOLVD prevention and treatment trials.

Section snippets

Study background and organization

The design, methods, and results of SOLVD have been reported elsewhere.1, 2, 4 In brief, 6797 individuals from Belgium, the USA, and Canada, with ejection fractions of 0·35 or less, were randomised to receive either enalapril or placebo for a median duration of 3·2 years. Patients who were not receiving treatment for heart failure at the time of randomisation were entered in the prevention trial, whereas those who were on treatment were entered in the treatment trial.

The present study was

Results

Follow-up data were available for 6784 of 6797 participants (99·8%). Five individuals in the enalapril group and eight in the placebo group were lost to follow-up (they could not be traced). In the prevention trial, median duration of follow-up was 11·2 years (IQR 10·3–12·1) from randomisation and 8·6 years (7·3–8·6) since the original study ended. In the treatment trial, median duration of follow-up was 12·1 years (11·4–13·0) from randomisation and 9·2 years (7·9–9·2) since the original study

Discussion

We showed that previous treatment with enalapril in patients with left ventricular systolic dysfunction during SOLVD resulted in a significant survival benefit that was seen beyond the original period of the two trials. In particular, our study extended the result of the SOLVD prevention trial (in which no clear reduction in mortality at the end of the trial was seen) by showing improved long-term survival after the original period of the study. From our data, we estimate that treatment of 1000

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