title: Association Between Use of Long-Acting Nitrates and Outcomes in Heart Failure With Preserved Ejection Fraction.
abstract: BACKGROUND
  Nitrates may be beneficial in heart failure with preserved ejection fraction (HFpEF) by enhancing cGMP signaling and improving hemodynamics, but real-world data on potential efficacy are lacking.
  
  
  RESULTS
  We linked the Swedish Heart Failure Registry to national registries withInternational Classification of Diseases, Tenth Revisioncomorbidity diagnoses and demographic and socioeconomic data. In HFpEF, defined as left ventricular ejection fraction ≥40%, we derived propensity scores for nitrate use using 52 baseline variables. The association between nitrate use and all-cause mortality and the composite of all-cause mortality or first heart failure hospitalization was assessed in a cohort matched 2:1 untreated to treated based on age and propensity score. In the overall HFpEF cohort (n=19 047; mean [SD] age, 76 [12] years; 46% women), nitrates were used in 17%, and the crude 1-year survival for treated versus untreated patients was 79% (95% confidence interval [CI], 78%-80%) versus 84% (95% CI, 83%-84%) respectively; hazard ratio was 1.48 (95% CI, 1.40-1.56;P<0.001) during a median 755-day follow-up. Matching yielded 2235 treated versus 4470 untreated patients, with 1-year survival of 80% (95% CI, 78%-82%) versus 79% (95% CI, 78%-81%) and hazard ratio of 1.06 (95% CI, 0.98-1.15;P=0.12). Nitrates were associated with worse composite outcome in the matched HFpEF cohort, with 1-year event-free survival of 62% (95% CI, 60%-64%) versus 65% (95% CI, 63%-66%) and hazard ratio of 1.11 (95% CI, 1.04-1.18;P=0.003). These patterns were reproduced in several consistency analyses.
  
  
  CONCLUSIONS
  In HFpEF, the use of nitrates was not associated with improvements in all-cause mortality or heart failure hospitalization.
authors.affiliation: From the Department of Cardiology, National University Heart Center, Singapore (S.L.L.); Department of Clinical Science and Education, Södersjukhuset (L.B.) and Department of Medicine (L.H.L.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medicine and Health Sciences (U.D.), Linköping University, Sweden; Department of Cardiology, National Heart Center, Singapore (C.S.P.L.); Duke-NUS Graduate Medical School, Singapore (C.S.P.L.); and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.).
authors.forename: Shir Lynn
authors.initials: SL
authors.lastname: Lim
authors.affiliation: From the Department of Cardiology, National University Heart Center, Singapore (S.L.L.); Department of Clinical Science and Education, Södersjukhuset (L.B.) and Department of Medicine (L.H.L.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medicine and Health Sciences (U.D.), Linköping University, Sweden; Department of Cardiology, National Heart Center, Singapore (C.S.P.L.); Duke-NUS Graduate Medical School, Singapore (C.S.P.L.); and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.).
authors.forename: Lina
authors.initials: L
authors.lastname: Benson
authors.affiliation: From the Department of Cardiology, National University Heart Center, Singapore (S.L.L.); Department of Clinical Science and Education, Södersjukhuset (L.B.) and Department of Medicine (L.H.L.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medicine and Health Sciences (U.D.), Linköping University, Sweden; Department of Cardiology, National Heart Center, Singapore (C.S.P.L.); Duke-NUS Graduate Medical School, Singapore (C.S.P.L.); and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.).
authors.forename: Ulf
authors.initials: U
authors.lastname: Dahlström
authors.affiliation: From the Department of Cardiology, National University Heart Center, Singapore (S.L.L.); Department of Clinical Science and Education, Södersjukhuset (L.B.) and Department of Medicine (L.H.L.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medicine and Health Sciences (U.D.), Linköping University, Sweden; Department of Cardiology, National Heart Center, Singapore (C.S.P.L.); Duke-NUS Graduate Medical School, Singapore (C.S.P.L.); and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.).
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.affiliation: From the Department of Cardiology, National University Heart Center, Singapore (S.L.L.); Department of Clinical Science and Education, Södersjukhuset (L.B.) and Department of Medicine (L.H.L.), Karolinska Institutet, Stockholm, Sweden; Department of Cardiology (U.D.) and Department of Medicine and Health Sciences (U.D.), Linköping University, Sweden; Department of Cardiology, National Heart Center, Singapore (C.S.P.L.); Duke-NUS Graduate Medical School, Singapore (C.S.P.L.); and Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden (L.H.L.). lars.lund@alumni.duke.edu.
authors.forename: Lars H
authors.initials: LH
authors.lastname: Lund
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D006760:Hospitalization; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000009:adverse effects / Q000627:therapeutic use*; D057216:Propensity Score; D020127:Recovery of Function; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013318:Stroke Volume / Q000187:drug effects*; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D009566:Nitrates; D014665:Vasodilator Agents
keywords: heart failure; hemodynamics; hospitalization; mortality; propensity score