Anticoagulation therapy in atrial fibrillation after intracranial hemorrhage


      The effect of oral anticoagulation therapy (OAT) in patients with atrial fibrillation (AF) with a history of intracranial hemorrhage (ICH) is poorly defined.


      The purpose of this study was to evaluate the efficacy and safety of OAT in patients with AF with an ICH history.


      We retrospectively compared the composite end point, including thromboembolic and major bleeding events, between patients with AF with a history of ICH who were (OAT group, n = 254) and those who were not (no-OAT group, n = 174) taking OAT.


      During a mean follow-up of 39.5 ± 31.9 months, 5.5 and 3.1 major bleeding events/100 patient-years were observed in the OAT and no-OAT groups, respectively (P = .024). Recurrent ICH was observed only in patient with OAT. Thromboembolic events occurred in 2.4 and 8.3 events/100 patient-years in OAT and no-OAT groups, respectively (P < .001). There was no significant differences in composite end points between OAT and no-OAT groups (11.5 events/100 patient-years vs 7.9 events/100 patient-years; P = .154). Patients with OAT who achieved a time-in-therapeutic range of ≥60% of the international normalized ratio of 2.0–3.0 demonstrated a better cumulative survival free of the composite end point (P < .001) than did patients without OAT. Early (<2 weeks) OAT after an index ICH did not improve composite end points because of the increased incidence of major bleeding events. However, OAT at 2 weeks after an index ICH was associated with decreased clinical events including thromboembolic events and composite end point.


      In patients with AF who require anticoagulation and have a history of ICH, maintaining optimal OAT with time-in-therapeutic range ≥ 60% and the initiation of OAT at least 2 weeks after an index ICH were associated with improved clinical outcomes

      Graphical Abstract


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Heart Rhythm
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Go A.S.
        • Hylek E.M.
        • Phillips K.A.
        • Chang Y.
        • Henault L.E.
        • Selby J.V.
        • Singer D.E.
        Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study.
        JAMA. 2001; 285: 2370-2375
        • Hart R.G.
        • Pearce L.A.
        • Aguilar M.I.
        Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation.
        Ann Intern Med. 2007; 146: 857-867
        • Hart R.G.
        • Diener H.C.
        • Yang S.
        • Connolly S.J.
        • Wallentin L.
        • Reilly P.A.
        • Ezekowitz M.D.
        • Yusuf S.
        Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: the RE-LY trial.
        Stroke. 2012; 43: 1511-1517
        • Flaherty M.L.
        • Kissela B.
        • Woo D.
        • Kleindorfer D.
        • Alwell K.
        • Sekar P.
        • Moomaw C.J.
        • Haverbusch M.
        • Broderick J.P.
        The increasing incidence of anticoagulant-associated intracerebral hemorrhage.
        Neurology. 2007; 68: 116-121
        • Connolly S.J.
        • Ezekowitz M.D.
        • Yusuf S.
        • et al.
        Dabigatran versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2009; 361: 1139-1151
        • Patel M.R.
        • Mahaffey K.W.
        • Garg J.
        • et al.
        Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.
        N Engl J Med. 2011; 365: 883-891
        • Granger C.B.
        • Alexander J.H.
        • McMurray J.J.
        • et al.
        Apixaban versus warfarin in patients with atrial fibrillation.
        N Engl J Med. 2011; 365: 981-992
        • Hori M.
        • Matsumoto M.
        • Tanahashi N.
        • et al.
        Rivaroxaban vs. warfarin in Japanese patients with non-valvular atrial fibrillation in relation to age.
        Circ J. 2014; 78: 1349-1356
        • Ogawa S.
        • Shinohara Y.
        • Kanmuri K.
        Safety and efficacy of the oral direct factor Xa inhibitor apixaban in Japanese patients with non-valvular atrial fibrillation: the ARISTOTLE-J study.
        Circ J. 2011; 75: 1852-1859
        • Farooqui A.
        • Hiser B.
        • Barnes S.L.
        • Litofsky N.S.
        Safety and efficacy of early thromboembolism chemoprophylaxis after intracranial hemorrhage from traumatic brain injury.
        J Neurosurg. 2013; 119: 1576-1582
        • Schulman S.
        • Angeras U.
        • Bergqvist D.
        • Eriksson B.
        • Lassen M.R.
        • Fisher W.
        Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients.
        J Thromb Haemost. 2010; 8: 202-204
        • Rosendaal F.R.
        • Cannegieter S.C.
        • van der Meer F.J.
        • Briet E.
        A method to determine the optimal intensity of oral anticoagulant therapy.
        Thromb Haemost. 1993; 69: 236-239
        • Hylek E.M.
        • Go A.S.
        • Chang Y.
        • Jensvold N.G.
        • Henault L.E.
        • Selby J.V.
        • Singer D.E.
        Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation.
        N Engl J Med. 2003; 349: 1019-1026
        • Gooley T.A.
        • Leisenring W.
        • Crowley J.
        • Storer B.E.
        Estimation of failure probabilities in the presence of competing risks: new representations of old estimators.
        Stat Med. 1999; 18: 695-706
        • Fine J.P.
        • Gray R.J.
        A proportional hazards model for the subdistribution of a competing risk.
        J Am Stat Assoc. 1999; 94: 496-509
        • Goldstein J.N.
        • Fazen L.E.
        • Wendell L.
        • et al.
        Risk of thromboembolism following acute intracerebral hemorrhage.
        Neurocrit Care. 2009; 10: 28-34
        • Christensen M.C.
        • Dawson J.
        • Vincent C.
        Risk of thromboembolic complications after intracerebral hemorrhage according to ethnicity.
        Adv Ther. 2008; 25: 831-841
        • January C.T.
        • Wann L.S.
        • Alpert J.S.
        • et al.
        2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Heart Rhythm Society.
        Circulation. 2014; 130: e199-e267
        • Camm A.J.
        • Lip G.Y.
        • De Caterina R.
        • Savelieva I.
        • Atar D.
        • Hohnloser S.H.
        • Hindricks G.
        • Kirchhof P.
        2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation—developed with the special contribution of the European Heart Rhythm Association.
        Europace. 2012; 14: 1385-1413
        • Nielsen P.B.
        • Larsen T.B.
        • Skjoth F.
        • Gorst-Rasmussen A.
        • Rasmussen L.H.
        • Lip G.Y.
        Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: a nationwide cohort study.
        Circulation. 2015; 132: 517-525
        • Kuramatsu J.B.
        • Gerner S.T.
        • Schellinger P.D.
        • et al.
        Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage.
        JAMA. 2015; 313: 824-836
        • Claassen D.O.
        • Kazemi N.
        • Zubkov A.Y.
        • Wijdicks E.F.
        • Rabinstein A.A.
        Restarting anticoagulation therapy after warfarin-associated intracerebral hemorrhage.
        Arch Neurol. 2008; 65: 1313-1318
        • Majeed A.
        • Kim Y.K.
        • Roberts R.S.
        • Holmstrom M.
        • Schulman S.
        • et al.
        Optimal timing of resumption of warfarin after intracranial hemorrhage.
        Stroke; a journal of cerebral circulation. 2010; 41: 2860-2866

      Linked Article