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Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm and Heart Failure With Reduced Ejection Fraction Treated With Warfarin or Aspirin

      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.
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      References

        • Lip G.Y.
        • Gibbs C.R.
        Does heart failure confer a hypercoagulable state? Virchow's triad revisited.
        J Am Coll Cardiol. 1999; 33: 1424-1426
        • Kalaria V.G.
        • Passannante M.R.
        • Shah T.
        • Modi K.
        • Weisse A.B.
        Effect of mitral regurgitation on left ventricular thrombus formation in dilated cardiomyopathy.
        Am Heart J. 1998; 135: 215-220
        • Massie B.M.
        • Collins J.F.
        • Ammon S.E.
        • Armstrong P.W.
        • Cleland J.G.F.
        • Ezekowitz M.
        • Jafri S.M.
        • Krol W.F.
        • O'Connor C.M.
        • Schulman K.A.
        • Teo K.
        • Warren S.R.
        • Investigators ftWT
        Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the warfarin and antiplatelet therapy in chronic heart failure (WATCH) trial.
        Circulation. 2009; 119: 1616-1624
        • Homma S.
        • Thompson J.L.
        • Pullicino P.M.
        • Levin B.
        • Freudenberger R.S.
        • Teerlink J.R.
        • Ammon S.E.
        • Graham S.
        • Sacco R.L.
        • Mann D.L.
        • Mohr J.P.
        • Massie B.M.
        • Labovitz A.J.
        • Anker S.D.
        • Lok D.J.
        • Ponikowski P.
        • Estol C.J.
        • Lip G.Y.
        • Di Tullio M.R.
        • Sanford A.R.
        • Mejia V.
        • Gabriel A.P.
        • del Valle M.L.
        • Buchsbaum R.
        Warfarin and aspirin in patients with heart failure and sinus rhythm.
        N Engl J Med. 2012; 366: 1859-1869
        • Lip G.Y.H.
        • Andreotti F.
        • Fauchier L.
        • Huber K.
        • Hylek E.
        • Knight E.
        • Lane D.A.
        • Levi M.
        • Marin F.
        • Palareti G.
        • Kirchhof P.
        • Collet J.-P.
        • Rubboli A.
        • Poli D.
        • Camm J.
        • Document reviewers
        Bleeding risk assessment and management in atrial fibrillation patients: a position document from the European Heart Rhythm Association, endorsed by the European Society of Cardiology Working Group on Thrombosis.
        Europace. 2011; 13: 723-746
        • Lip G.Y.H.
        • Frison L.
        • Halperin J.L.
        • Lane D.A.
        Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial fibrillation: The HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, labile INR, Elderly, Drugs/Alcohol Concomitantly) score.
        J Am Coll Cardiol. 2011; 57: 173-180
        • Beyth R.J.
        • Quinn L.M.
        • Landefeld C.S.
        Prospective evaluation of an index for predicting the risk of major bleeding in outpatients treated with warfarin.
        Am J Med. 1998; 105: 91-99
        • Gage B.F.
        • Yan Y.
        • Milligan P.E.
        • Waterman A.D.
        • Culverhouse R.
        • Rich M.W.
        • Radford M.J.
        Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF).
        Am Heart J. 2006; 151: 713-719
        • Fang M.C.
        • Go A.S.
        • Chang Y.
        • Borowsky L.H.
        • Pomernacki N.K.
        • Udaltsova N.
        • Singer D.E.
        A new risk scheme to predict warfarin-associated hemorrhage: the ATRIA (Anticoagulation and risk factors in atrial fibrillation) study.
        J Am Coll Cardiol. 2011; 58: 395-401
        • Apostolakis S.
        • Lane D.A.
        • Guo Y.
        • Buller H.
        • Lip G.Y.H.
        Performance of the HEMORR(2)HAGES, ATRIA, and HAS-BLED bleeding risk-prediction scores in patients with atrial fibrillation undergoing anticoagulation: the AMADEUS (evaluating the use of SR34006 compared to warfarin or acenocoumarol in patients with atrial fibrillation) study.
        J Am Coll Cardiol. 2012; 60: 861-867
        • Aspinall S.L.
        • DeSanzo B.E.
        • Trilli L.E.
        • Good C.B.
        Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care.
        J Gen Intern Med. 2005; 20: 1008-1013
        • Pullicino P.
        • Thompson J.L.
        • Barton B.
        • Levin B.
        • Graham S.
        • Freudenberger R.S.
        Warfarin versus aspirin in patients with reduced cardiac ejection fraction (WARCEF): rationale, objectives, and design.
        J Card Fail. 2006; 12: 39-46
        • Schulman S.
        • Kearon C.
        Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients.
        J Thromb Haemost. 2005; 3: 692-694
        • Pencina M.J.
        • D'Agostino Sr., R.B.
        • D'Agostino Jr., R.B.
        • Vasan R.S.
        Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond.
        Stat Med. 2008; 27 (discussion 207–112): 157-172
        • Pencina M.J.
        • D'Agostino Sr., R.B.
        • Steyerberg E.W.
        Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers.
        Stat Med. 2011; 30: 11-21
        • Eikelboom J.W.
        • Connolly S.J.
        Warfarin in heart failure.
        N Engl J Med. 2012; 366: 1936-1938
        • Burgess S.
        • Crown N.
        • Louzada M.L.
        • Dresser G.
        • Kim R.B.
        • Lazo-Langner A.
        Clinical performance of bleeding risk scores for predicting major and clinically relevant non-major bleeding events in patients receiving warfarin.
        J Thromb Haemost. 2013; 11: 1647-1654
        • Homma S.
        • Thompson J.L.P.
        • Sanford A.R.
        • Mann D.L.
        • Sacco R.L.
        • Levin B.
        • Pullicino P.M.
        • Freudenberger R.S.
        • Teerlink J.R.
        • Graham S.
        • Mohr J.P.
        • Massie B.M.
        • Labovitz A.J.
        • Di Tullio M.R.
        • Gabriel A.P.
        • Lip G.Y.H.
        • Estol C.J.
        • Lok D.J.
        • Ponikowski P.
        • Anker S.D.
        Benefit of warfarin compared with aspirin in patients with heart failure in sinus rhythm: a subgroup analysis of WARCEF, a randomized controlled trial.
        Circ Heart Fail. 2013; 6: 988-997
        • Roldán V.
        • Marín F.
        • Manzano-Fernández S.
        • Gallego P.
        • Vílchez J.A.
        • Valdés M.
        • Vicente V.
        • Lip G.Y.H.
        The HAS-BLED score has better prediction accuracy for major bleeding than CHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibrillation.
        J Am Coll Cardiol. 2013; 62: 2199-2204
        • Oldgren J.
        • Alings M.
        • Darius H.
        • Diener H.-C.
        • Eikelboom J.
        • Ezekowitz M.D.
        • Kamensky G.
        • Reilly P.A.
        • Yang S.
        • Yusuf S.
        • Wallentin L.
        • Connolly S.J.
        Risks for stroke, bleeding, and death in patients with atrial fibrillation receiving dabigatran or warfarin in relation to the CHADS2 score: a subgroup analysis of the RE-LY trial.
        Ann Intern Med. 2011; 155: 660-667
        • Lane D.A.
        • Lip G.Y.
        Use of the CHA(2)DS(2)-VASc and HAS-BLED scores to aid decision making for thromboprophylaxis in nonvalvular atrial fibrillation.
        Circulation. 2012; 126: 860-865
        • Ruff C.T.
        • Giugliano R.P.
        • Braunwald E.
        • Hoffman E.B.
        • Deenadayalu N.
        • Ezekowitz M.D.
        • Camm A.J.
        • Weitz J.I.
        • Lewis B.S.
        • Parkhomenko A.
        • Yamashita T.
        • Antman E.M.
        Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.
        Lancet. 2014; 383: 955-962
        • Camm A.J.
        • Kirchhof P.
        • Lip G.Y.
        • Schotten U.
        • Savelieva I.
        • Ernst S.
        • Van Gelder I.C.
        • Al-Attar N.
        • Hindricks G.
        • Prendergast B.
        • Heidbuchel H.
        • Alfieri O.
        • Angelini A.
        • Atar D.
        • Colonna P.
        • De Caterina R.
        • De Sutter J.
        • Goette A.
        • Gorenek B.
        • Heldal M.
        • Hohloser S.H.
        • Kolh P.
        • Le Heuzey J.Y.
        • Ponikowski P.
        • Rutten F.H.
        Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC).
        Eur Heart J. 2010; 31: 2369-2429