Long-term effect of atenolol on ejection fraction, symptoms, and exercise variables in patients with advanced left ventricular dysfunction.

Aims: We recently reported a beneficial clinical effect of atenolol, a beta (1) selective adrenergic antagonist, in 100 ambulatory heart failure patients with low left ventricular ejection fraction (LVEF, less than or equal to 25%) who were receiving background therapy with 40 mg/day enalapril. In this sub-study, we investigated the effects of atenolol vs placebo on LVEF, New York Heart Association (NYHA) class, workload, and peak oxygen consumption (VO2). Methods and Results: We included 43 patients (23 receiving atenolol, 20 receiving placebo) who had similar entry characteristics. We evaluated LVEF once a year and evaluated workload, pVO(2), and NYHA class before and after 6, 12, and 24 months. Repeated measures of analysis of variance were used for comparison of serial measurements. After 2 years, both atenolol (18%, 5% vs 36% +/- 18%, p < 0.05) and placebo (18% +/- 5% vs 23% +/- 5%, p < 0.05) increased LVEF, with a more pronounced effect of atenolol (p = 0.02), which also changed NYHA class distribution more favorably over time (p < 0.05). Workload and peak VO2 increased after atenolol (110 +/- 47 vs 140 +/- 48 watts, p < 0.05, and 18 +/- 5 vs 21 +/- 5 ml/kg/min, p < 0.05) but not after placebo (100 +/- 35 vs 110 +/- 38 watts, p < 0.05, between groups and 17 +/- 4 vs 19 +/- 7 ml/kg/min, not significant, between groups). Conclusions: In patients with advanced heart failure who tolerate long-term atenolol vs placebo treatment added to high-dose enalapril for 2 years without cardiac events, systolic left ventricular function is markedly improved. These patients experience greater relief of symptoms and increased exercise tolerance.