Effect of beta-blockade on heart rate variability in patients with coronary artery disease

J Am Coll Cardiol. 1994 May;23(6):1370-7. doi: 10.1016/0735-1097(94)90379-4.


Objectives: This study assessed the effects of beta-blockade on heart rate variability in patients with coronary artery disease and determined whether the effects of metoprolol in a controlled-release formulation and atenolol differ with regard to electrocardiographic measures of cardiac autonomic control.

Background: Low heart rate variability is common in coronary artery disease and is associated with increased mortality. Beta-adrenergic blocking drugs may increase heart rate variability in healthy subjects, but there is limited knowledge of whether they are able to modify heart rate variability in patients with uncomplicated coronary artery disease.

Methods: In a randomly allocated, double-blind crossover study with three 2-week treatment periods, 200 mg of controlled-release metoprolol once a day, 100 mg of atenolol once a day or placebo once a day were administered in 18 male patients with stable coronary artery disease. The 24-h heart rate variability was measured in both the time and frequency domains.

Results: Beta-blockade induced a significant increase in heart rate variability, but no significant differences were found between atenolol and metoprolol. The average 24-h high frequency power increased by 64% after atenolol and by 62% after metoprolol. The root-mean-square successive difference of normal RR intervals increased by 70% after atenolol and by 62% after metoprolol, and the standard deviations of RR intervals increased by 20% and 16%, respectively. Beta-blockade had no significant effects on the amplitude of the circadian rhythm of heart rate variability, although both metoprolol and atenolol blunted the abrupt decrease of high frequency power after arousal.

Conclusions: Beta-blockade by metoprolol and atenolol enhance the heart rate variability in patients with coronary artery disease. This may contribute to the protective effects of beta-blockade in ischemic heart disease.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Atenolol / administration & dosage
  • Atenolol / blood
  • Atenolol / pharmacology*
  • Circadian Rhythm / drug effects
  • Coronary Disease / blood
  • Coronary Disease / drug therapy*
  • Coronary Disease / epidemiology
  • Coronary Disease / physiopathology
  • Double-Blind Method
  • Electrocardiography, Ambulatory / drug effects
  • Electrocardiography, Ambulatory / statistics & numerical data
  • Heart Rate / drug effects*
  • Humans
  • Least-Squares Analysis
  • Male
  • Metoprolol / administration & dosage
  • Metoprolol / blood
  • Metoprolol / pharmacology*
  • Middle Aged
  • Signal Processing, Computer-Assisted
  • Time Factors


  • Atenolol
  • Metoprolol