Baseline Functional Class and Therapeutic Efficacy of Common Heart Failure Interventions: A Systematic Review and Meta-analysis

Can J Cardiol. 2015 Jun;31(6):792-9. doi: 10.1016/j.cjca.2014.12.031. Epub 2015 Jan 7.


Background: New York Heart Association (NYHA) functional class provides important prognostic information and is often used to select patients for cardiovascular therapies, yet, the effect of NYHA class on therapeutic efficacy has not been systematically studied.

Methods: In this systematic review and meta-analysis we compared the relative and absolute mortality benefit of 5 common heart failure interventions (angiotensin-converting enzyme [ACE] inhibitors, β-blockers, mineralocorticoid receptor antagonists [MRAs], implantable cardioverter defibrillator [ICD], and cardiac resynchronization therapy [CRT]) across NYHA class. We included 26 randomized clinical trials of these interventions that reported all-cause mortality stratified according to baseline NYHA class in 36,406 patients.

Results: Pooled relative risk for NYHA I/II vs. III/IV strata were similar for ACE inhibitors (0.90 vs. 0.88), β-blockers (0.72 vs. 0.79), MRA (0.79 vs. 0.75), and CRT (0.80 vs. 0.80), with all heterogeneity P > 0.8. Conversely, ICD efficacy was greater for class I/II (relative risk, 0.65 vs 0.86, heterogeneity P = 0.02). The pooled absolute risk difference was smaller for NYHA I/II vs III/IV with ACE inhibitors (-0.02 vs. -0.06, P = 0.12), β-blockers (-0.02 vs. -0.05, P = 0.047), MRA (-0.03 vs. -0.11, P = 0.001), and CRT (-0.01 vs. -0.04, P = 0.036), but was similar across NYHA class for the ICD (-0.07 vs. -0.05; P = 0.27).

Conclusions: Relative mortality reductions with most interventions were independent of baseline NYHA class. However, ICD efficacy was greater with NYHA I/II vs. III/IV limitation, and absolute benefit was greater with higher NYHA class. For interventions other than the ICD, there is little evidence supporting use of NYHA class as a rigid criterion for selecting heart failure therapies.

Publication types

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

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Cardiac Pacing, Artificial / methods
  • Cardiac Pacing, Artificial / mortality
  • Cardiac Resynchronization Therapy / methods*
  • Cardiac Resynchronization Therapy / mortality
  • Cause of Death*
  • Defibrillators, Implantable
  • Drug Therapy, Combination
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / mortality*
  • Heart Failure / therapy*
  • Humans
  • Male
  • Mineralocorticoid Receptor Antagonists / therapeutic use
  • Prognosis
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Survival Analysis
  • Treatment Outcome


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Mineralocorticoid Receptor Antagonists