Effect of Carvedilol on Survival in Severe Chronic Heart Failure - COPERNICUS
Effect of Carvedilol on Survival in Severe Chronic Heart Failure.
Beta-blocking agents reduce the risk of hospitalization and death in patients with mild-to moderate heart failure, but little is known about their effects in severe heart failure.
Patients Enrolled: 2289
Patients who required intensive care, had marked fluid retention or were receiving intravenous vasodilators or positive inotropic drugs were excluded.
The authors evaluated 2,289 patients who had symptoms of heart failure at rest or on minimal exertion, who were clinically euvolemic and who had an ejection fraction of less than 25%. 1,133 patients were randomly assigned to placebo and 1,156 patients to treatment with carvedilol for a mean period of 10.4 months, during which standard therapy for heart failure was continued. Patients who required intensive care, had marked fluid retention or were receiving intravenous vasodilators or positive inotropic drugs were excluded.
There were 190 deaths in the placebo group and 130 deaths in the carvedilol group. This difference reflected 35% decrease in the risk of death with carvedilol. A total of 507 patients died or were hospitalized in the placebo group, as compared with 425 in the carvedilol group. This difference reflected a 24% decrease in the combined risk of death or hospitalization with carvedilol. Fewer patients in the carvedilol group than in the placebo group withdrew because of adverse effects or for other reasons (p=0.02).
The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also found in the patients with severe heart failure who were evaluated in this trial.
In searching for explanations for the lack of benefit of bucindolol in the BEST Trial, greater severity of heart failure was one possibility. The subsequent results of the COPERNICUS Trial, to the contrary, argue strongly that beta adrenergic blockade improves survival and clinical outcome in more severe heart failure, when patients are not fluid overloaded or acutely decompensated. “Euvolemia” remains a clinical criteria and difficult to objectively measure. However, it is notable that this study was terminated early by its Data and Safety Monitoring Board due to the magnitude of clinical benefit of carvedilol.
1. Packer M, Coats AJS, Fowler MB, et al. for the Carvedilol Prospective Randomized Cumulative Survival Study Group. N Engl J Med 2001;334:1651-8.
Keywords: Carbazoles, Heart Failure, Clinical Trials Data Monitoring Committees, Propanolamines, Adrenergic Antagonists, Hospitalization, Vasodilator Agents
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