Dragos Vinereanu1, Susanna R Stevens2, John H Alexander2, Sana M Al-Khatib2, Alvaro Avezum3, Marıa Cecilia Bahit4, Christopher B Granger2, Renato D Lopes2, Sigrun Halvorsen5, Michael Hanna6, Steen Husted7, Elaine M Hylek8, Andrei D Mărgulescu9, Lars Wallentin10, Dan Atar11. 1. University of Medicine and Pharmacy Carol Davila, Bucharest, Romania Department of Cardiology, University and Emergency Hospital of Bucharest, 169 Splaiul Independentei, Sector 5, Bucharest, Romania vinereanu@gmail.com. 2. Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA. 3. Dante Pazzanese Institute of Cardiology, Sao Paulo, Brazil. 4. INECO Neurociencias Oroño, Rosario, Argentina. 5. Oslo University Hospital and University of Oslo, Oslo, Norway. 6. Bristol-Myers Squibb, Princeton, NJ, USA. 7. Hospital Unit West and Aarhus University Hospital, Aarhus, Denmark. 8. Boston University Medical Center, Boston, MA, USA. 9. University of Medicine and Pharmacy Carol Davila, Bucharest, Romania Department of Cardiology, University and Emergency Hospital of Bucharest, 169 Splaiul Independentei, Sector 5, Bucharest, Romania. 10. Uppsala Clinical Research Center and Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 11. Department of Cardiology B, Oslo University Hospital, and Institute of Clinical Sciences, University of Oslo, Oslo, Norway.
Abstract
AIM: To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation. METHODS AND RESULTS:Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive eitherwarfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex. CONCLUSION: In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women. TRIAL REGISTRATION: ARISTOTLE ClinicalTrials.gov number, NCT00412984. Published on behalf of the European Society of Cardiology. All rights reserved.
RCT Entities:
AIM: To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation. METHODS AND RESULTS:Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex. CONCLUSION: In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women. TRIAL REGISTRATION: ARISTOTLE ClinicalTrials.gov number, NCT00412984. Published on behalf of the European Society of Cardiology. All rights reserved.
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