Shaun G Goodman1, Daniel M Wojdyla2, Jonathan P Piccini2, Harvey D White3, John F Paolini4, Christopher C Nessel5, Scott D Berkowitz4, Kenneth W Mahaffey2, Manesh R Patel2, Matthew W Sherwood2, Richard C Becker2, Jonathan L Halperin6, Werner Hacke7, Daniel E Singer8, Graeme J Hankey9, Gunter Breithardt10, Keith A A Fox11, Robert M Califf12. 1. Canadian Heart Research Centre and Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada. Electronic address: goodmans@chrc.net. 2. Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina. 3. Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand. 4. Bayer HealthCare Pharmaceuticals, Montville, New Jersey. 5. Janssen Research and Development, Raritan, New Jersey. 6. Cardiovascular Institute, Mount Sinai Medical Center, New York, New York. 7. Ruprecht-Karls-University, Heidelberg, Germany. 8. Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 9. Royal Perth Hospital, Perth, Australia. 10. Hospital of the University of Münster, Münster, Germany. 11. University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, Scotland, United Kingdom. 12. Duke Clinical Research Institute and Duke Translational Medicine Institute, Duke University Medical Center, Durham, North Carolina.
Abstract
OBJECTIVES: This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). BACKGROUND: The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. METHODS: The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. RESULTS: The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, andanemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. CONCLUSIONS:Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767).
RCT Entities:
OBJECTIVES: This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). BACKGROUND: The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. METHODS: The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. RESULTS: The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. CONCLUSIONS:Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767).
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