BENEFICIAL-EFFECTS OF METOPROLOL IN HEART-FAILURE ASSOCIATED WITH CORONARY-ARTERY DISEASE - A RANDOMIZED TRIAL

Objectives. This clinical trial was performed to determine the safety and clinical impact of titrated metoprolol therapy in patients with heart failure, documented coronary artery disease and a low ejection fraction. Background. Despite known cardiodepressant effects, long-term use of beta adrenergic antagonists appears to be beneficial in patients with idiopathic dilated cardiomyopathy. However, this therapy has not been critically evaluated in patients with heart failure and coronary artery disease. Methods. In 50 patients with heart failure, known coronary artery disease and an ejection fraction less than or equal to 0.40, we examined the impact of metoprolol therapy in a 6-month double-blind, placebo-controlled randomized trial, assessing the frequency of heart failure exacerbations and changes in symptoms (New York Heart Association functional class), ejection fraction and exercise duration. Placebo-treated patients who completed 6-month follow up studies then underwent a trial with metoprolol therapy (crossover group). Results. Metoprolol was titrated to a mean maximal dose of 87 mg/day (range 25 to 100) without serious adverse reactions. During double blind therapy, use of a beta blocker was associated with a significant reduction in the number of hospital admissions (4% vs. 32%, p < 0.05), overall improved functional class (p = 0.02), increased ejection fraction (4 +/- 7% [mean +/- SD] compared with 0 +/- 6%, p < 0.05) and a greater increase in exercise duration (193 +/- 276 vs. 38 +/- 213 s with placebo, p < 0.01). Crossover outcome paralleled the favorable impact seen during randomized metoprolol therapy. Conclusions. Cautious use of titrated metoprolol appears to be safe and beneficial when added, to standard heart failure therapy in patients with dilated cardiomyopathy associated with coronary artery disease.