Stephan Windecker1, Renato D Lopes2, Tyler Massaro2, Charlotte Jones-Burton3, Christopher B Granger2, Ronald Aronson3, Gretchen Heizer2, Shaun G Goodman4,5, Harald Darius6, W Schuyler Jones2, Michael Aschermann7, David Brieger8, Fernando Cura9, Thomas Engstrøm10, Viliam Fridrich11, Sigrun Halvorsen12, Kurt Huber13, Hyun-Jae Kang14, Jose L Leiva-Pons15, Basil S Lewis16, German Malaga17, Nicolas Meneveau18,19, Bela Merkely20, Davor Milicic21, João Morais22, Tatjana S Potpara23,24, Dimitar Raev25, Manel Sabaté26, Suzanne de Waha-Thiele27, Robert C Welsh4,28, Denis Xavier29, Roxana Mehran30, John H Alexander2. 1. Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Switzerland (S.W.). 2. Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (R.D.L., T.M., C.B.G., G.H., W.S.J., J.H.A.). 3. Bristol-Myers Squibb, Lawrenceville, NJ (C.J.-B., R.A.). 4. Canadian VIGOUR Center, University of Alberta, Edmonton, Canada (S.G.G., R.C.W.). 5. Terrence Donnelly Heart Centre, St Michael's Hospital, University of Toronto, Ontario, Canada (S.G.G.). 6. Vivantes Neukoelln Medical Center, Berlin, Germany (H.D.). 7. Charles University, Prague, Czech Republic (M.A.). 8. Concord Clinical School, ANZAC Research Institute, University of Sydney, Australia (D.B.). 9. Instituto Cardiovascular de Buenos Aires and Sanatorio Anchorena, Argentina (F.C.). 10. Rigshospital, University of Copenhagen, Denmark (T.E.). 11. National Institute of Cardiovascular Diseases, Bratislava, Slovakia (V.F.). 12. Oslo University Hospital Ulleval, University of Oslo, Norway (S.H.). 13. Wilhelminenhospital and Sigmund Freud University, Medical School, Vienna, Austria (K.H.). 14. Seoul National University Hospital, Seoul National University, Korea (H.-J.K.). 15. Hospital Central Dr Ignacio Morones Prieto, San Luis Potosi, Mexico (J.L.L.-P.). 16. Cardiovascular Clinical Research Institute, Lady Davis Carmel Medical Center, Haifa, Israel (B.S.L.). 17. CONEVID School of Medicine, Universidad Peruana Cayetano Heredia, Lima, Peru (G.M.). 18. University Hospital Jean Minjoz, Besançon, France (N.M.). 19. EA3920, University of Burgundy Franche-Comté, Besançon, France (N.M.). 20. Semmelweis University Heart and Vascular Center, Budapest, Hungary (B.M.). 21. University of Zagreb School of Medicine, University Hospital Centre, Croatia (D.M.). 22. Hospital de Santo André, Leiria, Portugal (J.M.). 23. School of Medicine, Belgrade University, Serbia (T.S.P.). 24. Clinical Centre of Serbia, Belgrade (T.S.P.). 25. University Hospital St Anna, Sofia, Bulgaria (D.R.). 26. University Heart Centre Lübeck, University Hospital Schleswig-Holstein, Germany (S.d.W.-T.). 27. German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Lübeck, Lübeck (S.d.W.-T.). 28. Mazankowski Alberta Heart Institute, Edmonton, Canada (R.C.W.). 29. St John's Medical College and Research Institute, Bangalore, India (D.X.). 30. Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, and Cardiovascular Research Foundation, New York, NY (R.M.).
Abstract
BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoingelective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.
RCT Entities:
BACKGROUND: The safety and efficacy of antithrombotic regimens may differ between patients with atrial fibrillation who have acute coronary syndromes (ACS), treated medically or with percutaneous coronary intervention (PCI), and those undergoing elective PCI. METHODS: Using a 2×2 factorial design, we compared apixaban with vitamin K antagonists and aspirin with placebo in patients with atrial fibrillation who had ACS or were undergoing PCI and were receiving a P2Y12 inhibitor. We explored bleeding, death and hospitalization, as well as death and ischemic events, by antithrombotic strategy in 3 prespecified subgroups: patients with ACS treated medically, patients with ACS treated with PCI, and those undergoing elective PCI. RESULTS: Of 4614 patients enrolled, 1097 (23.9%) had ACS treated medically, 1714 (37.3%) had ACS treated with PCI, and 1784 (38.8%) had elective PCI. Apixaban compared with vitamin K antagonist reduced International Society on Thrombosis and Haemostasis major or clinically relevant nonmajor bleeding in patients with ACS treated medically (hazard ratio [HR], 0.44 [95% CI, 0.28-0.68]), patients with ACS treated with PCI (HR, 0.68 [95% CI, 0.52-0.89]), and patients undergoing elective PCI (HR, 0.82 [95% CI, 0.64-1.04]; Pinteraction=0.052) and reduced death or hospitalization in the ACS treated medically (HR, 0.71 [95% CI, 0.54-0.92]), ACS treated with PCI (HR, 0.88 [95% CI, 0.74-1.06]), and elective PCI (HR, 0.87 [95% CI, 0.72-1.04]; Pinteraction=0.345) groups. Compared with vitamin K antagonists, apixaban resulted in a similar effect on death and ischemic events in the ACS treated medically, ACS treated with PCI, and elective PCI groups (Pinteraction=0.356). Aspirin had a higher rate of bleeding than did placebo in patients with ACS treated medically (HR, 1.49 [95% CI, 0.98-2.26]), those with ACS treated with PCI (HR, 2.02 [95% CI, 1.53-2.67]), and those undergoing elective PCI (HR, 1.91 [95% CI, 1.48-2.47]; Pinteraction=0.479). For the same comparison, there was no difference in outcomes among the 3 groups for the composite of death or hospitalization (Pinteraction=0.787) and death and ischemic events (Pinteraction=0.710). CONCLUSIONS: An antithrombotic regimen consisting of apixaban and a P2Y12 inhibitor without aspirin provides superior safety and similar efficacy in patients with atrial fibrillation who have ACS, whether managed medically or with PCI, and those undergoing elective PCI compared with regimens that include vitamin K antagonists, aspirin, or both. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02415400.
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