Renato D Lopes1, Gretchen Heizer1, Ronald Aronson1, Amit N Vora1, Tyler Massaro1, Roxana Mehran1, Shaun G Goodman1, Stephan Windecker1, Harald Darius1, Jia Li1, Oleg Averkov1, M Cecilia Bahit1, Otavio Berwanger1, Andrzej Budaj1, Ziad Hijazi1, Alexander Parkhomenko1, Peter Sinnaeve1, Robert F Storey1, Holger Thiele1, Dragos Vinereanu1, Christopher B Granger1, John H Alexander1. 1. From the Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC (R.D.L., G.H., A.N.V., T.M., C.B.G., J.H.A.); Bristol-Myers Squibb, Princeton, NJ (R.A., J.L.); Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, and Cardiovascular Research Foundation, New York (R.M.); Canadian VIGOUR Centre, University of Alberta, Edmonton (S.G.G.), and the Terrence Donnelly Heart Centre, St. Michael's Hospital, University of Toronto, Toronto (S.G.G.) - both in Canada; Swiss Cardiovascular Center, Bern, Switzerland (S.W.); Vivantes Neukoelln Medical Center, Berlin (H.D.), and Heart Center Leipzig, Department of Internal Medicine-Cardiology, University of Leipzig, Leipzig (H.T.) - both in Germany; Pirogov Russian National Research Medical University, Moscow (O.A.); Instituto de Neurología Cognitiva (INECO) Neurociencias Oroño, Fundación INECO, Rosario, Argentina (M.C.B.); Hospital Israelita Albert Einstein, São Paulo (O.B.); Postgraduate Medical School, Grochowski Hospital, Warsaw, Poland (A.B.); the Department of Medical Sciences, Cardiology, and Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden (Z.H.); the National Scientific Center, Strazhesko Institute of Cardiology, Kiev, Ukraine (A.P.); University Hospitals Leuven, University of Leuven, Leuven, Belgium (P.S.); the Department of Infection, Immunity, and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom (R.F.S.); and University of Medicine and Pharmacy Carol Davila, University and Emergency Hospital, Bucharest, Romania (D.V.).
Abstract
BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receiveapixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, withoutaspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).
RCT Entities:
BACKGROUND: Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. METHODS: In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y12 inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. RESULTS: Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P = 0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. CONCLUSIONS: In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y12 inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both. (Funded by Bristol-Myers Squibb and Pfizer; AUGUSTUS ClinicalTrials.gov number, NCT02415400.).
Authors: Salina P Waddy; Allen J Solomon; Adan Z Becerra; Julia B Ward; Kevin E Chan; Chyng-Wen Fwu; Jenna M Norton; Paul W Eggers; Kevin C Abbott; Paul L Kimmel Journal: J Am Soc Nephrol Date: 2020-02-20 Impact factor: 10.121
Authors: David W Jones; Sheharyar Minhas; Joseph J Fierro; Devarshi Ardeshna; Aranyak Rawal; Brandon Cave; Samarth P Shah; Rami N Khouzam Journal: Ann Transl Med Date: 2019-09