Background: Clinical trials have shown that β-adrenergic blocking drugs are effective and well tolerated in patients with mild to moderate heart failure, but the utility and safety of these drugs in patients with advanced disease have not been evaluated. Methods and Results: We enrolled 56 patients with severe chronic heart failure into a double-blind, placebo-controlled study of the vasodilating β-blocker carvedilol. All patients had advanced heart failure, as evidenced by a mean left ventricular ejection fraction of 0.16±0.01 and a mean maximal oxygen consumption of 13.6±0.6 mL · kg-1 · min-1 despite digitalis, diuretics, and an angiotensin-converting enzyme inhibitor (if tolerated). After a 3-week, open-label, up-titration period, 49 of the 56 patients were assigned (in a double-blind fashion using a 2:1 randomization) to receive either carvedilol (25 mg BID, n=33) or matching placebo (n=16) for 14 weeks, while background therapy remained constant. Hemodynamic and functional variables were measured at the start and end of the study. Compared with the placebo group, patients in the carvedilol group showed improved cardiac performance, as reflected by an increase in left ventricular ejection fraction (P=.005) and stroke volume index (P=.010) and a decrease in pulmonary wedge pressure, mean right atrial pressure, and systemic vascular resistance (P=.003, .002, and .017, respectively). In addition, compared with placebo, patients treated with carvedilol benefited clinically, as shown by an improvement in symptom scores (P=.002), functional class (P=.013), and submaximal exercise tolerance (P=.006). The combined risk of death, worsening heart failure, and life-threatening ventricular tachyarrhythmia was lower in the carvedilol group than in the placebo group (P=.028), but carvedilol-treated patients had more dizziness and advanced heart block. Conclusions: Carvedilol produces clinical and hemodynamic improvement in patients who have severe heart failure despite treatment with angiotensin-converting enzyme inhibitors.
- heart failure
- receptors, adrenergic, beta
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)