Effect of beta 1 blockade with atenolol on progression of heart failure inpatients pretreated with high-dose enalapril

Background: The survival benefit of beta -blocker treatment in patients wit h heart failure has been established in recent trials. Yet, the impact of b eta -blockers added on high dose angiotensin converting enzyme inhibitors h as not been reported. Aims: To investigate the effect of atenolol, a hydrop hilic, selective beta1-adrenergic antagonist, added on enalapril 40 mg/day in patients with advanced left ventricular dysfunction in a double-blind pl acebo-controlled trial. Methods: One hundred and nineteen patients with cla ss II or III heart failure, left ventricular ejection fraction less than or equal to 25% and treatment with 40 mg enalapril daily were given an initia l challenge dose of atenolol 12.5 mg. One hundred patients (54 with idiopat hic, 28 with ischemic, 18 with other dilated cardiomyopathy) tolerated chal lenge and were randomized to atenolol (maintenance dose 89 +/- 11 mg/day, r ange 50-100 mg/day) or placebo. The primary endpoint was combined worsening heart failure or death within 2 years, the secondary endpoint was hospital ization for cardiac events. Results: After 395 +/- 266 days interim analysi s revealed a significant difference between the atenolol and placebo group (log rank P < 0.01) and the trial was concluded. Twenty-seven patients had developed worsening heart failure (8 in the atenolol group vs. 19 in the pl acebo group) and 13 patients had died (5 in the atenolol vs. 8 in the place bo group). Overall there were 23 hospitalizations for cardiac events (6 in the atenolol group vs. 21 in the placebo group, P = 0.07); 17 hospitalizati ons were due to worsening heart failure (5 in the atenolol group, 12 in the placebo-group, P = 0.05) and 10 due to arrhythmias (1 in the atenolol grou p vs. 9 in the placebo group, P < 0.01) Conclusions. The data suggest that in patients with advanced left ventricular dysfunction, beta -blockers can provide substantial benefits supplementary to that already achieved with hi gh dose enalapril treatment. (C) 2000 European Society of Cardiology. All r ights reserved.