title: 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.
  
  
  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.
authors.affiliation: Koç University, School of Medicine, Department of Cardiology, Istanbul, Turkey. Electronic address: dilekural@yandex.com.
authors.forename: Dilek
authors.initials: D
authors.lastname: Ural
authors.affiliation: Kocaeli University, Hereke Vocational School, Department of Biostatistics, Kocaeli, Turkey.
authors.forename: Aysen Şimşek
authors.initials: AŞ
authors.lastname: Kandemir
authors.affiliation: Derince Education and Research Hospital, Department of Cardiology, Kocaeli, Turkey.
authors.forename: Kurtuluş
authors.initials: K
authors.lastname: Karaüzüm
authors.affiliation: Kocaeli University, School of Medicine, Department of Biostatistics, Kocaeli, Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Baydemir
authors.affiliation: Kocaeli University, School of Medicine, Department of Cardiology, Kocaeli, Turkey.
authors.forename: İrem Yılmaz
authors.initials: İY
authors.lastname: Karaüzüm
authors.affiliation: Derince Education and Research Hospital, Department of Cardiology, Kocaeli, Turkey.
authors.forename: Serdar
authors.initials: S
authors.lastname: Bozyel
authors.affiliation: Kocaeli University, School of Medicine, Department of Cardiology, Kocaeli, Turkey.
authors.forename: Güliz
authors.initials: G
authors.lastname: Kozdağ
authors.affiliation: Kocaeli University, School of Medicine, Department of Cardiology, Kocaeli, Turkey.
authors.forename: Ayşen Ağaçdiken
authors.initials: AA
authors.lastname: Ağır
mesh_terms: D000368:Aged; D002317:Cardiovascular Agents / Q000145:classification / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009026:Mortality; D057216:Propensity Score; D012189:Retrospective Studies; D012307:Risk Factors; D013318:Stroke Volume; D016019:Survival Analysis; D014421:Turkey / Q000453:epidemiology; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D002317:Cardiovascular Agents; D007548:Isosorbide Dinitrate
keywords: Nitrates; heart failure; mortality