Fast track —ArticlesEffect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial
Introduction
The efficacy of β-blockers in reducing major coronary events and improving short-term and long-term outcome has established their beneficial role in the management of acute myocardial infarction.1, 2, 3 However, the randomised trials whose results showed these effects were done before thrombolysis or primary angioplasty were used for reperfusion, and before the introduction of angiotensin-converting-enzyme (ACE) inhibitors. β-blockers have now been shown to reduce mortality and morbidity substantially, and improve left-ventricular function in patients with chronic heart failure when given together with ACE inhibitors.4, 5, 6, 7
Since coronary heart disease is a major cause of heart failure, attention has focused once more on the use of β-blockers in patients with acute myocardial infarction. Although there have been many randomised, placebo-controlled trials of β blockade in acute myocardial infarction, none has studied patients with confirmed left-ventricular systolic dysfunction who might also have had clinical evidence of heart failure during the index hospital admission. Post-hoc subgroup analyses of previous trials, however, have suggested a similar mortality benefit in patients with heart failure.8, 9, 10 Conversely, several trials of ACE inhibitors have conclusively shown substantial improvement in mortality and morbidity in this group of patients.11, 12, 13
Registries from Europe and the USA indicate that the use of β-blockers in eligible patients post myocardial infarction is substantially lower than would be expected from the convincingly positive results of the older trials.14, 15 One explanation for this finding could be the absence of contemporary data from trials in the post thrombolytic era, specifically in patients who have substantial left-ventricular dysfunction, who might also have heart failure, and in whom ACE inhibitors will have been prescribed. We designed the Carvedilol Post- Infarct Survival Control in LV Dysfunction (CAPRICORN) study to test the hypothesis that the addition of carvedilol to standard modern management of acute myocardial infarction in patients with leftventricular dysfunction with or without heart failure would improve outcome in terms of mortality and morbidity.
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Patients
The CAPRICORN study, whose design and protocol have been published elsewhere,16 was a multicentre, double-blind, randomised controlled trial of carvedilol versus placebo involving 17 countries and 163 centres worldwide. Eligible patients were aged 18 years or older with a stable, definite myocardial infarction occurring 3–21 days before randomisation. Other inclusion criteria were: left-ventricular ejection fraction of 40% or less by two-dimensional echocardiography or by radionuclide or
Results
We recruited 1959 patients, of whom 975 were assigned carvedilol and 984 placebo, and who were followed up for a mean of 1·3 years (figure 1). The trial continued to its planned conclusion when 633 primary endpoints had been validated. In total, 707 such events were judged by the endpoints committee to have occurred.
Baseline characteristics, which were similar between the two groups, are shown in Table 1. The mean left-ventricular ejection fraction was 32·8%, and intravenous diuretics and
Discussion
The results of this study show substantial benefit from carvedilol with respect to major coronary events. The 23% relative reduction in mortality is identical to that reported in a meta-analysis of 22 long-term, randomised, controlled trials of β-blockers in acute myocardial infarction.3 However, in CAPRICORN, the all-cause mortality rate on placebo was 15% compared with 12% on carvedilol after an average followup of 1·3 years, whereas in the previous trials, the average mortality was 10% on
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