Beta-blockade improves morbidity and mortality in New York Heart Association (NYHA) functional class II-IV heart failure. Several meta-analyses have shown an increased left ventricular ejection fraction and a decreased combined risk of death and hospitalization for heart failure with P-blockers, including metoprolol, bisoprolol, carvedilol, and bucindolol.
With the exception of the Beta-blocker Evaluation Survival Trial (BEST), all the other trials have shown a uniform decrease in total mortality of approximately 35%. The second Cardiac Insufficiency Bisoprolol Study (CIBIS II) showed a significant decrease in the incidence of sudden death. Carvedilol has been the only drug tested in severe heart failure: the CarvedilOl ProspEctive RaN-domlzed Cumulative Survival (COPERNICUS) study found the same highly significant effect on mortality.
The Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF) and CIBIS II, each with Pj-selective agents, showed decreases in mortality and hospitalization and an increase in left ventricular ejection fraction.
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Which beta-blocker for heart failure? Am Heart J. 2001;141:899-907.
Kukin ML, Kalman J, Chamey RH, et al. Prospective, randomized comparison of effect of long-term treatment with metoprolol or carvedilol on sympceptor blockade and documented antioxidant activity. Extensive clinical trial evidence shows that carvedilol enhances the left ventricular ejection fraction and decreases mortality and hospitalization.
Two small studies comparing metoprolol and carvedilol found significant improvement in symptoms, exercise capacity, and left ventricular ejection fraction. The two drugs did not differ significantly in these respects. However, carvedilol had significantly greater effect on blood pressure, left ventricular end-diastolic dimensions, and normalization of the mitral E wave deceleration time. Carvedilol appears better tolerated in the short term, especially if hemodynamic status is poor, perhaps due to compensation by peripheral vasodilatation for the initial reduction in myocardial inotropism. The Carvedilol Or Metoprolol Evaluation (European) Trial (COMET) should provide more definitive data on the comparative benefits of P,-and combined nonselective P-blockade + a-blockade.
At present, however, the clinical trial evidence indicates that metoprolol, carvedilol, and bisoprolol are safe and effective in heart failure, with significant mortality and morbidity benefits. No such benefits have been found with first-generation p-blockers or P-blockers with intrinsic sympathomimetic activity toms, exercise, ejection fraction, and oxidative stress in heart failure. Circulation. 1999;99:2645-2651.
Sanderson JE, Chan SK, Yip G, et al. Beta-blockade in heart failure: a comparison of carvedilol with metoprolol. J Am Coll Cardiol. 1999;34:1522-1528.