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European Journal of Heart Failure 2000 2(4):407-412; doi:10.1016/S1388-9842(00)00120-3
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© 2000 European Society of Cardiology

Effect of β1 blockade with atenolol on progression of heart failure in patients pretreated with high-dose enalapril

Barbara Sturm, Richard Pacher, Jeanette Strametz-Juranek, Rudolf Berger, Bernhard Frey and Brigitte Stanek*

Department of Cardiology, University of Vienna Währinger Gürtel 18-20, A-1090 Vienna, Austria

* Corresponding author. Tel.: +431-40400-4616; fax: +431-4081148. E-mail address: etanzl{at}pop3.kard.akh-wien.ac.at (B. Stanek).


  Abstract

Background: The survival benefit of β-blocker treatment in patients with heart failure has been established in recent trials. Yet, the impact of β-blockers added on high dose angiotensin converting enzyme inhibitors has not been reported.

Aims: To investigate the effect of atenolol, a hydrophilic, selective β1-adrenergic antagonist, added on enalapril 40 mg/day in patients with advanced left ventricular dysfunction in a double-blind placebo-controlled trial.

Methods: One hundred and nineteen patients with class II or III heart failure, left ventricular ejection fraction ≤25% and treatment with 40 mg enalapril daily were given an initial challenge dose of atenolol 12.5 mg. One hundred patients (54 with idiopathic, 28 with ischemic, 18 with other dilated cardiomyopathy) tolerated challenge and were randomized to atenolol (maintenance dose 89±11 mg/day, range 50–100 mg/day) or placebo. The primary endpoint was combined worsening heart failure or death within 2 years, the secondary endpoint was hospitalization for cardiac events.

Results: After 395±266 days interim analysis 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 placebo group) and 13 patients had died (5 in the atenolol vs. 8 in the placebo group). Overall there were 23 hospitalizations for cardiac events (6 in the atenolol group vs. 21 in the placebo group, P=0.07); 17 hospitalizations 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 group vs. 9 in the placebo group, P<0.01)

Conclusions: The data suggest that in patients with advanced left ventricular dysfunction, β-blockers can provide substantial benefits supplementary to that already achieved with high dose enalapril treatment.

Key Words: Heart failure • Advanced left ventricular dysfunction • High-dose enalapril • β-Blockade • Progression of disease

Received April 24, 2000; Revised June 28, 2000; Accepted August 16, 2000


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