CAPRICORN: A Multinational, Randomized, Double-Blind Study of the Effects of Carvedilol on Mortality and Morbidity in Patients with Left Ventricular Dysfunction after Myocardial Infarction
Henry J. Dargie
University of Glasgow Royal Infirmary, Glasgow, Scotland, UK

Previous studies investigating the value of beta-blocker therapy in patients with acute myocardial infarction were done many years ago, before the availability of therapies with thrombolysis and ACE inhibitors and before the widespread use of aspirin. The CAPRICORN trial results show that long-term use of carvedilol in patients treated following acute myocardial infarction with left ventricular dysfunction substantially reduced the incidence of all-cause and cardiovascular mortality and of recurrent non-fatal myocardial infarctions.

The CAPRICORN trial is the first large-scale, placebo-controlled trial of beta-blocker therapy for patients with acute myocardial infarction to be done in the modern era, with its widespread use of aspirin and availability of thrombolysis and angiotensin-converting enzyme (ACE) inhibitors. In addition, many of the earlier trials excluded patients with heart failure. CAPRICORN studied the use of carvedilol among patients who had acute myocardial infarction with left ventricular dysfunction -- that is, patients who had a decreased ejection fraction (<40%) with or without clinical heart failure. The study included 1,959 patients randomized to receive a placebo or carvedilol at doses titrated up to 25 mg twice daily. (Dr. Dargie noted that 75% of patients in the active treatment group received the maximum dose and tolerated it well.) Treatment was initiated within 3 to 21 days after the acute event; the average time for initiation of treatment was approximately 10 days. Patients were followed for a mean of 1.3 years.

Dr. Dargie said that the data show carvedilol reduced all-cause mortality by 23% (p = .03), non-fatal myocardial infarctions by 41% (p = .01), and all-cause mortality or non-fatal myocardial infarction by 29% (p = .002). There was a trend toward decreased hospitalizations in the carvedilol group, but it was not statistically significant. Dr. Dargie said: "Please note that the number of patients we need to treat with carvedilol for 1 year to prevent 1 death is 43, which is a very favorable number and is comparable to the number for ACE inhibitors. However, this effect with carvedilol is additive to the effect of ACE inhibitors, so if patients receive both drugs they will receive the combined beneficial effects."

Dr. Dargie concluded: "The results of the CAPRICORN trial bridge the gap between treatment of patients in the Cardiac Care Unit and the treatment of congestive heart failure. Since the Cardiac Care Unit is in many cases the 'birthplace' of cases of congestive heart failure, we may expect carvedilol therapy in patients with acute myocardial infarction with left ventricular dysfunction to reduce the number of patients in this situation who progress to overt heart failure."



Reporter: Andre Weinberger, MD


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