Effects of drug, biobehavioral and exercise therapies on heart rate variability in coronary artery disease: a systematic review

Eur J Cardiovasc Prev Rehabil. 2008 Aug;15(4):386-96. doi: 10.1097/HJR.0b013e3283030a97.


Background: Heart rate variability (HRV) is reported as a surrogate index for clinical outcome in trials of secondary prevention strategies for coronary artery disease (CAD), but a standardized guide for interpreting HRV change is not established.

Design: We evaluated HRV change in trials with CAD patients who received conventional medications (beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors), biobehavioral treatment (psychotropics, biofeedback, relaxation) or exercise training.

Methods: Medline, Pubmed, Psycinfo, the Cochrane database, and Embase were searched until July 2007, without language restriction. We identified 33 randomized controlled trials. Two reviewers independently abstracted all trials using a standardized form. A hierarchy of frequency and time domain HRV indices defined outcome.

Results: A random-effects model yielded an overall pooled standardized mean difference (SMD) between treatment and control groups of moderate magnitude across treatment classes, based on a composite of time and frequency domain indices (SMD=0.40, P<0.0001), or only time or frequency indices (SMD=0.37 and 0.43, respectively, both P<0.0001). This change was equivalent to an increase in standard deviation of all normal-to-normal RR intervals of 9.0 ms (95% Confidence Interval, CI, 7.3, 10.7 ms) or a relative increase of 15.9% (95% CI, 13.2, 18.6%). To detect HRV change of this magnitude, a hypothetical trial would require a sample size of 660 patients for conventional medications or 1232 patients for all treatment classes.

Conclusion: Pharmacologic, biobehavioral and exercise strategies for secondary prevention of CAD significantly increase HRV. This review provides a framework to assist efforts to evaluate the contribution of HRV change to CAD prognosis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Behavior Therapy*
  • Cardiovascular Agents / therapeutic use*
  • Coronary Artery Disease / physiopathology*
  • Coronary Artery Disease / therapy
  • Exercise Therapy*
  • Heart Rate*
  • Humans
  • Randomized Controlled Trials as Topic


  • Cardiovascular Agents