Association between use of renin-angiotensin system antagonists and mortality in patients with heart failure and preserved ejection fraction

JAMA. 2012 Nov 28;308(20):2108-17. doi: 10.1001/jama.2012.14785.


Context: Heart failure with preserved ejection fraction (HFPEF) may be as common and as lethal as heart failure with reduced ejection fraction (HFREF). Three randomized trials of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ie, renin-angiotensin system [RAS] antagonists) did not reach primary end points but may have had selection bias or been underpowered.

Objective: To test the hypothesis that use of RAS antagonists is associated with reduced all-cause mortality in an unselected population with HFPEF.

Design, setting, and patients: Prospective study using the Swedish Heart Failure Registry of 41,791 unique patients registered from 64 hospitals and 84 outpatient clinics between 2000 and 2011. Of these, 16,216 patients with HFPEF (ejection fraction ≥40%; mean [SD] age, 75 [11] years; 46% women) were either treated (n = 12,543) or not treated (n = 3673) with RAS antagonists. Propensity scores for RAS antagonist use were derived from 43 variables. The association between use of RAS antagonists and all-cause mortality was assessed in a cohort matched 1:1 based on age and propensity score and in the overall cohort with adjustment for propensity score as a continuous covariate. To assess consistency, separate age and propensity score-matched analyses were performed according to RAS antagonist dose in patients with HFPEF and in 20,111 patients with HFREF (ejection fraction <40%) in the same registry.

Main outcome measure: All-cause mortality.

Results: In the matched HFPEF cohort, 1-year survival was 77% (95% CI, 75%-78%) for treated patients vs 72% (95% CI, 70%-73%) for untreated patients, with a hazard ratio (HR) of 0.91 (95% CI, 0.85-0.98; P = .008). In the overall HFPEF cohort, crude 1-year survival was 86% (95% CI, 86%-87%) for treated patients vs 69% (95% CI, 68%-71%) for untreated patients, with a propensity score-adjusted HR of 0.90 (95% CI, 0.85-0.96; P = .001). In the HFPEF dose analysis, the HR was 0.85 (95% CI, 0.78-0.83) for 50% or greater of target dose vs no treatment (P < .001) and 0.94 (95% CI, 0.87-1.02) for less than 50% of target dose vs no treatment (P = .14). In the age and propensity score-matched HFREF analysis, the HR was 0.80 (95% CI, 0.74-0.86; P < .001).

Conclusion: Among patients with heart failure and preserved ejection fraction, the use of RAS antagonists was associated with lower all-cause mortality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Female
  • Heart Failure / drug therapy*
  • Heart Failure / mortality*
  • Humans
  • Male
  • Propensity Score
  • Prospective Studies
  • Registries / statistics & numerical data
  • Renin-Angiotensin System / drug effects*
  • Stroke Volume
  • Survival Analysis
  • Sweden / epidemiology


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors