Mathieu Kerneis1, Megan K Yee1, Roxana Mehran2, Tarek Nafee1, Christoph Bode3, Jonathan L Halperin2, Eric D Peterson4, Freek W A Verheugt5, Peter Wildgoose6, Martin van Eickels7, Gregory Y H Lip8, Marc Cohen9, Keith A A Fox10, C Michael Gibson1. 1. Division of Cardiovascular Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (M.K., M.K.Y., T.N., C.M.G.). 2. Cardiovascular Institute, Mount Sinai Medical Center, Icahn School of Medicine at Mount Sinai, NY (R.M., J.L.H.). 3. Heart Center, Department for Cardiology and Angiology I, University of Freiburg, Germany (C.B.). 4. Duke Clinical Research Institute, Durham, NC (E.D.P.). 5. Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, the Netherlands (F.W.A.V.). 6. Janssen Pharmaceuticals, Inc, Beerse, Belgium, Inc, Titusville, NJ (P.W.). 7. Bayer Pharmaceuticals, Inc, Berlin, Germany (M.v.E.). 8. Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom; and Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.). 9. Division of Cardiology, Newark Beth Israel Medical Center, Newark, NJ (M.C.). 10. Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, United Kingdom (K.A.A.F.).
Abstract
BACKGROUND: Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapyreduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy. METHODS:Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (Group 1, n=709); rivaroxaban 2.5 mg bid plusdual antiplatelet therapy (DAPT; Group 2, n=709); and warfarin plus DAPT (Group 3, n=706). Before randomization, subjects were stratified according to a prespecified duration of DAPT (1, 6, or 12 months). After the prespecified DAPT duration, subjects in Group 2 were switched to rivaroxaban 15 mg plus low dose aspirin, and those in Group 3 were switched to VKA plus low dose aspirin. The Wei, Lin, and Weissfeld time to multiple events method was used to compare the occurrence of all bleeding and cardiovascular rehospitalizations among subjects on a novel oral anticoagulant versus VKA based double therapy. RESULTS: A total of 906 subjects were prespecified to a 1 or 6 months DAPT duration and received at least one dose of study drug. Twenty subjects (3.3%) assigned to novel oral anticoagulant+SAPT, and 15 (5.1%) subjects assigned to VKA+SAPT experienced multiple rehospitalizations. In total, 124 (20.3%) events occurred among subjects on novel oral anticoagulant+SAPT compared with 87 (29.6%) among subjects on VKA+SAPT (hazard ratio=0.65 [95% CI, 0.45-0.93], P=0.008). CONCLUSIONS: Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.
RCT Entities:
BACKGROUND: Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapy reduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy. METHODS:Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (Group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (DAPT; Group 2, n=709); and warfarin plus DAPT (Group 3, n=706). Before randomization, subjects were stratified according to a prespecified duration of DAPT (1, 6, or 12 months). After the prespecified DAPT duration, subjects in Group 2 were switched to rivaroxaban 15 mg plus low dose aspirin, and those in Group 3 were switched to VKA plus low dose aspirin. The Wei, Lin, and Weissfeld time to multiple events method was used to compare the occurrence of all bleeding and cardiovascular rehospitalizations among subjects on a novel oral anticoagulant versus VKA based double therapy. RESULTS: A total of 906 subjects were prespecified to a 1 or 6 months DAPT duration and received at least one dose of study drug. Twenty subjects (3.3%) assigned to novel oral anticoagulant+SAPT, and 15 (5.1%) subjects assigned to VKA+SAPT experienced multiple rehospitalizations. In total, 124 (20.3%) events occurred among subjects on novel oral anticoagulant+SAPT compared with 87 (29.6%) among subjects on VKA+SAPT (hazard ratio=0.65 [95% CI, 0.45-0.93], P=0.008). CONCLUSIONS: Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.