Incidence and Outcomes of Gastrointestinal Hemorrhage in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: Results From the ROCKET AF Trial.

SESSION TYPE: Arrhythmia and Coronary Artery DiseasePRESENTED ON: Monday, October 22, 2012 at 11:15 AM - 12:30 PMPURPOSE: Gastrointestinal (GI) hemorrhage is a common complication of anticoagulant therapy. We investigated the incidence and outcomes of GI hemorrhage among patients in the ROCKET AF study.METHODS: In ROCKET AF, 14,264 patients with nonvalvular atrial fibrillation (AF) were randomized to rivaroxaban or dose-adjusted warfarin. This post hoc analysis was performed on all patients while receiving study medication until two days after the last dose, using adjudicated data from the blinded, independent clinical events committee.RESULTS: The composite principal safety endpoint for GI bleeding events (upper, lower, rectal) occurred more frequently in patients receiving rivaroxaban (n=394) than warfarin (n=290; 3.61 vs. 2.60%/year; HR 1.39; 95% CI 1.19-1.61). Both major (2.00 vs. 1.24%/year; HR 1.61; 95% CI 1.30-1.99) and non-major, clinically relevant (1.75 vs. 1.39%/year; HR 1.26; 95% CI 1.20-1.55) bleeding occurred more frequently on rivaroxaban than on warfarin. Compared with those without (n=13,552), patients with major GI bleeding (n=684) were more likely to be older, current/prior smokers, have prior GI bleeding, mild anemia at baseline and a lower creatinine clearance, and less likely to be female or have prior stroke/TIA. Major bleeding events were defined most often by hemoglobin drop or transfusion of >2 units. The most severe of these events, as measured by transfusion of >4 units, was similar between treatment groups (rivaroxaban n=49, warfarin n=47). One patient on rivaroxaban and five on warfarin developed fatal GI bleeding.CONCLUSIONS: Both major and non-major, clinically relevant GI bleeding were more common in patients with AF taking rivaroxaban than warfarin. The most severe of these events were balanced between treatment groups. There were fewer fatal GI bleeds on rivaroxaban and the absolute fatality rate was very low.CLINICAL IMPLICATIONS: Rivaroxaban is associated with more GI bleeding than warfarin, but less life-threatening or fatal GI bleeding. A careful benefit-risk assessment is needed for high-risk patients.DISCLOSURE: Christopher Nessel: Employee: Johnson & Johnson Research & DevelopmentKenneth Mahaffey: Grant monies (from industry related sources): AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Eli Lilly, GSK, Johnson & Johnson, Merck, Momenta Pharmaceuticals, Novartis, Portola, Pozen, Regado Biotechnologies, Sanofi-Aventis, Schering-Plough, The Medicines Company, Consultant fee, speaker bureau, advisory committee, etc.: AstraZeneca, Johnson & Johnson, Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Eli Lilly, GSK, Merck, Novartis, Ortho/McNeill, Pfizer, Polymedix, Sanofi-Aventis, Schering-PloughJonathan Piccini: Grant monies (from industry related sources): Johnson & Johnson, Boston Scientific, Consultant fee, speaker bureau, advisory committee, etc.: Medtronic, Forest Laboratories, Sanofi Aventis, Johnson & JohnsonGuohua Pan: Employee: Johnson & Johnson Research & DevelopmentManesh Patel: Consultant fee, speaker bureau, advisory committee, etc.: Johnson & Johnson, Bayer, Ortho McNeill, Janssen, GenzymeRichard Becker: Grant monies (from industry related sources): Bayer, Johnson & JohnsonDaniel Singer: Grant monies (from sources other than industry): Supported in part by the Eliot B. and Edith C. Shoolman fund of the Massachusetts General Hospital, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Boehringer Ingelheim, BMS, Daiichi Sankyo, Johnson & Johnson, Pfizer, Sanofi AventisJonathan Halperin: Consultant fee, speaker bureau, advisory committee, etc.: Johnson & Johnson, Bayer, Boehringer Ingelheim, BMS, PfizerGraeme Hankey: Consultant fee, speaker bureau, advisory committee, etc.: Johnson & Johnson, Bayer, Sanofi-Aventis, Boehringer IngelheimScott Berkowitz: Employee: Bayer HealthCareKeith Fox: Grant monies (from industry related sources): Bayer, Lilly, Boehringer Ingelheim, Sanofi-Aventis, GSK, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Lilly, Boehringer Ingelheim, Sanofi-Aventis, GSKRobert Califf: Grant monies (from industry related sources): Johnson & Johnson, Consultant fee, speaker bureau, advisory committee, etc.: Johnson & JohnsonNo Product/Research Disclosure InformationJanssen Research & Development, Raritan, NJ.