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 Lip8,9, Marc Cohen10, Keith A A Fox11, 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, New York, 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. Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom (G.Y.H.L.). 9. Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L.). 10. Division of Cardiology, Newark Beth Israel Medical Center, NJ (M.C.). 11. Centre for Cardiovascular Science, University of Edinburgh and Royal Infirmary of Edinburgh, United Kingdom (K.A.A.F.).
Abstract
BACKGROUND: Among atrial fibrillation patients undergoing percutaneous coronary intervention enrolled in PIONEER AF-PCI (An Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention), it is unclear if the observed reduction in bleeding events with rivaroxaban regimens is consistent across a range of the international normalized ratio (INR) among subjects administrated Vitamin K antagonist (VKA)-triple therapy. This analysis compares the occurrence of clinically significant bleeding between rivaroxaban and VKA strategies, according to INR stability of subjects administrated VKA. METHODS AND RESULTS: A total of 2124 atrial fibrillation patients undergoing percutaneous coronary intervention 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 (group 2, n=709); and warfarin plus dual antiplatelet therapy (group 3, n=706). Subjects assigned to the VKA group were stratified according to time in therapeutic range and time spent with an INR >3. Kaplan-Meier estimates were calculated for clinically significant bleeding through 1 year and hazard ratios were derived using Cox Proportional Hazards models. Among group 3, 93.4% of the participants had a time in therapeutic range available (mean time in therapeutic range=65.0±24.8%). Both groups 1 and 2 were associated with a reduction in clinically significant bleeding compared with subjects in group 3, regardless of the time in therapeutic range (hazard ratio ranges=0.53-0.71 and 0.57-0.76; respectively, P<0.05 for all). Rivaroxaban strategies were associated with a reduction in clinically significant bleeding compared with VKA regardless of the proportion of time spent with an INR >3 (hazard ratio ranges=0.59-0.67 and 0.42-0.69; P<0.05 for all). CONCLUSIONS: Among atrial fibrillation patients undergoing percutaneous coronary intervention, rivaroxaban-based therapy was superior to warfarin plus dual antiplatelet therapy in lowering bleeding outcomes regardless of the INR stability. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01830543.
RCT Entities:
BACKGROUND: Among atrial fibrillationpatients undergoing percutaneous coronary intervention enrolled in PIONEER AF-PCI (An Open-Label, Randomized, Controlled, Multicenter Study Exploring Two Treatment Strategies of Rivaroxaban and a Dose-Adjusted Oral Vitamin K Antagonist Treatment Strategy in Subjects With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention), it is unclear if the observed reduction in bleeding events with rivaroxaban regimens is consistent across a range of the international normalized ratio (INR) among subjects administrated Vitamin K antagonist (VKA)-triple therapy. This analysis compares the occurrence of clinically significant bleeding between rivaroxaban and VKA strategies, according to INR stability of subjects administrated VKA. METHODS AND RESULTS: A total of 2124 atrial fibrillationpatients undergoing percutaneous coronary intervention 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 (group 2, n=709); and warfarin plus dual antiplatelet therapy (group 3, n=706). Subjects assigned to the VKA group were stratified according to time in therapeutic range and time spent with an INR >3. Kaplan-Meier estimates were calculated for clinically significant bleeding through 1 year and hazard ratios were derived using Cox Proportional Hazards models. Among group 3, 93.4% of the participants had a time in therapeutic range available (mean time in therapeutic range=65.0±24.8%). Both groups 1 and 2 were associated with a reduction in clinically significant bleeding compared with subjects in group 3, regardless of the time in therapeutic range (hazard ratio ranges=0.53-0.71 and 0.57-0.76; respectively, P<0.05 for all). Rivaroxaban strategies were associated with a reduction in clinically significant bleeding compared with VKA regardless of the proportion of time spent with an INR >3 (hazard ratio ranges=0.59-0.67 and 0.42-0.69; P<0.05 for all). CONCLUSIONS: Among atrial fibrillationpatients undergoing percutaneous coronary intervention, rivaroxaban-based therapy was superior to warfarin plus dual antiplatelet therapy in lowering bleeding outcomes regardless of the INR stability. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01830543.