CARVEDILOL IMPROVES LEFT-VENTRICULAR FUNCTION AND SYMPTOMS IN CHRONIC HEART-FAILURE - A DOUBLE-BLIND RANDOMIZED STUDY

Objectives. This study assessed the safety and efficacy of carvedilol in patients with heart failure caused by idiopathic or ischemic cardiomyopathy. Background. Carvedilol is a mildly beta(1)-selective beta-adrenergic blocking agent with vasodilator properties. Beta-blockade may be beneficial in patients with heart failure, but the effects of carvedilol are not known. Methods. Sixty patients with heart failure (New York Heart Association functional classes II to IV) and left ventricular ejection fraction less than or equal to 0.35 were enrolled in the study. All patients tolerated challenge with carvedilol, 3.125 mg twice a day, and were randomized to receive carvedilol (n = 36) versus placebo (n = 24). Study medication was titrated over 1 month from 6.25 to 25 mg twice a day (<75 kg) or 50 mg twice a day (>75 kg) and continued for 3 months. One placebo treated and two carvedilol-treated patients did not complete the study. Results. Carvedilol therapy resulted in a significant reduction in heart rate and mean pulmonary artery and pulmonary capillary wedge pressures and a significant increase in stroke volume and left ventricular stroke work. Left ventricular ejection fraction increased 52% in the carvedilol group (from 0.21 to 0.32, p < 0.0001 vs. placebo group). Carvedilol-treated patients also reported a significant lessening of heart failure symptoms (p < 0.05 vs. placebo group). Submaximal exercise duration tended to increase with carvedilol therapy (from 688 +/- 31 s to 871 +/- 32 s), but this change was not significantly different from that with placebo therapy by between-group analysis. Peak oxygen consumption during maximal exercise did not change. Conclusions. Long-term carvedilol therapy improves rest cardiac function and lessens symptoms in patients with heart failure.