Effect of Oral Nitrates on All-Cause Mortality and Hospitalization in Heart Failure Patients with Reduced Ejection Fraction: A Propensity-Matched Analysis

J Card Fail. 2017 Apr;23(4):286-292. doi: 10.1016/j.cardfail.2017.02.006. Epub 2017 Feb 21.

Abstract

Background: Hydralazine-nitrate combination is recommended for patients with heart failure with reduced ejection fraction (HFrEF)/systolic heart failure who are symptomatic despite guideline-directed medical therapy (GDMT). Use of nitrates alone for this indication is not well-established. This study aims to evaluate the effect of oral nitrates on all-cause mortality and hospitalization in HFrEF patients using GDMT.

Methods and results: Nitrate prescription at discharge and its association with all-cause mortality and heart failure hospitalization were examined in a propensity-matched analysis of 648 HFrEF patients followed for a median of 56 months. A total of 269 (42%) patients died during that period. In Cox regression analysis, nitrate usage was associated with a slightly increased mortality risk compared with not using nitrates (hazard ratio 1.29; 95% confidence interval 1.01-1.65; P = .040), which continued modestly after the propensity-matched analysis (hazard ratio 1.26; 95% confidence interval 0.95-1.68; P = .102). In both prematch and propensity-matched analyses, nitrate use was not associated with risk of rehospitalization. No significant effect was detected on subgroups stratified by coronary artery disease, age, gender, and background medical therapy.

Conclusions: In this study, oral nitrate use alone in addition to GDMT did not affect all-cause mortality and hospitalization risk in HFrEF patients during a long-term follow-up. There was even a modest tendency for increased risk of mortality.

Keywords: Nitrates; heart failure; mortality.

MeSH terms

  • Aged
  • Cardiovascular Agents / classification
  • Cardiovascular Agents / therapeutic use
  • Female
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Heart Failure* / mortality
  • Heart Failure* / physiopathology
  • Hospitalization / statistics & numerical data*
  • Humans
  • Isosorbide Dinitrate / therapeutic use*
  • Male
  • Middle Aged
  • Mortality
  • Propensity Score
  • Retrospective Studies
  • Risk Factors
  • Stroke Volume
  • Survival Analysis
  • Turkey / epidemiology
  • Ventricular Dysfunction, Left / physiopathology

Substances

  • Cardiovascular Agents
  • Isosorbide Dinitrate