title: Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm and Heart Failure With Reduced Ejection Fraction Treated With Warfarin or Aspirin.
abstract: We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin.
authors.affiliation: Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, New York. Electronic address: sy2357@cumc.columbia.edu.
authors.forename: Siqin
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York.
authors.forename: Bin
authors.initials: B
authors.lastname: Cheng
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York.
authors.forename: Richard
authors.initials: R
authors.lastname: Buchsbaum
authors.affiliation: Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Ralph L
authors.initials: RL
authors.lastname: Sacco
authors.affiliation: Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York.
authors.forename: Bruce
authors.initials: B
authors.lastname: Levin
authors.affiliation: Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, New York.
authors.forename: Marco R
authors.initials: MR
authors.lastname: Di Tullio
authors.affiliation: Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York.
authors.forename: Min
authors.initials: M
authors.lastname: Qian
authors.affiliation: Department of Medicine, Washington University, St. Louis, Missouri.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.affiliation: Kent Institute of Medicine and Health Sciences, University of Kent, Canterbury, United Kingdom.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Pullicino
authors.affiliation: Division of Cardiology, Department of Medicine, Lehigh Valley Hospital, Allentown, Pennsylvania.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Freudenberger
authors.affiliation: Section of Cardiology, San Francisco VA Medical Center and School of Medicine, University of California San Francisco, San Francisco, California.
authors.forename: John R
authors.initials: JR
authors.lastname: Teerlink
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, New York.
authors.forename: J P
authors.initials: JP
authors.lastname: Mohr
authors.affiliation: Division of Cardiology, Department of Medicine, SUNY Upstate Medical University, Buffalo, New York.
authors.forename: Susan
authors.initials: S
authors.lastname: Graham
authors.affiliation: Department of Cardiovascular Medicine, University of South Florida, Tampa, Florida.
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Labovitz
authors.affiliation: Centro Neurológico de Tratamiento y Rehabilitación, Buenos Aires, Argentina.
authors.forename: Conrado J
authors.initials: CJ
authors.lastname: Estol
authors.affiliation: Department of Cardiology, Deventer Hospital, Deventer, The Netherlands.
authors.forename: Dirk J
authors.initials: DJ
authors.lastname: Lok
authors.affiliation: Department of Heart Diseases, Wroclaw Medical University, Military Hospital, Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Ponikowski
authors.affiliation: Department of Innovative Clinical Trials, University Medical Centre Göttingen, Göttingen, Germany.
authors.forename: Stefan D
authors.initials: SD
authors.lastname: Anker
authors.affiliation: Department of Biostatistics, Columbia University Mailman School of Public Health, New York, New York.
authors.forename: John L P
authors.initials: JL
authors.lastname: Thompson
authors.affiliation: Division of Cardiology, Department of Medicine, Columbia University Medical Center, New York, New York.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D006470:Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D020521:Stroke / Q000209:etiology / Q000517:prevention & control*; D013318:Stroke Volume / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014859:Warfarin / Q000009:adverse effects*
chemical_list: D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D014859:Warfarin; D001241:Aspirin