Effect of oral nitrates on all-cause mortality and hospitalization in heart failure patients with reduced ejection fraction: a propensity-matched analysis

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.