Prospective, randomized comparison of effect of long-term treatment with metoprolol or carvedilol on symptoms, exercise, ejection fraction, and oxidative stress in heart failure

Background-With beta-blocker use becoming more prevalent in treating chronic heart failure (CHF), the choice of drugs raises important theoretical and practical questions. Although the second-generation compound metoprolol is beta(1)-selective, the third-generation compound carvedilol is beta-nonselective, with ancillary pharmacological properties including alpha-blockade and antioxidant effects. A prospective comparison of these 2 agents can address the issue of optimal adrenergic blockade in selecting agents for therapy in CHF. Methods and Results-Sixty-seven patients with symptomatic stable heart failure were randomly assigned to receive either carvedilol or metoprolol in addition to standard therapy for CHF. Measured variables included symptoms, exercise, ejection fraction, and thiobarbituric acid-reactive substances (TBARS) as an indirect marker of free radical activity. Metoprolol and carvedilol were well tolerated, and both patient groups showed beneficial effects of beta-blocker therapy in each of the measured parameters, with no between-group differences. Ejection fraction increased over 6 months from 18+/-6.3% to 23+/-8.7% (P<0.005) with metoprolol and from 19+/-8.5% to 25+/-9.9% (P<0.0005) with carvedilol (P=NS between groups), With metoprolol, TBARS values decreased from 4.7+/-0.9 nmol/ml at baseline to 4.2+/-1.5 nmol/ml at month 4 to 3.9+/-1.0 nmol/mL at month 6 (P<0.0001). With carvedilol, there was a parallel decline from 4.7+/-1.4 to 4.2+/-1.3 to 4.1+/-1.2 nmol/mL over the same time frame (P<0.025), with no between-group difference in these changes. Conclusions-Carvedilol and metoprolol showed parallel beneficial effects in the measured parameters over 6 months, with no relevant between-group differences in this heart failure population.