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

Eur J Heart Fail. 2000 Dec;2(4):407-12. doi: 10.1016/s1388-9842(00)00120-3.


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

Aims: To investigate the effect of atenolol, a hydrophilic, selective beta1-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 < or = 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, beta-blockers can provide substantial benefits supplementary to that already achieved with high dose enalapril treatment.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / administration & dosage
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Atenolol / therapeutic use*
  • Disease Progression
  • Double-Blind Method
  • Enalapril / administration & dosage
  • Enalapril / therapeutic use*
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / mortality
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Patient Selection


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Atenolol
  • Enalapril