Matthew W Sherwood1, Christopher C Nessel2, Anne S Hellkamp3, Kenneth W Mahaffey4, Jonathan P Piccini3, Eun-Young Suh2, Richard C Becker3, Daniel E Singer5, Jonathan L Halperin6, Graeme J Hankey7, Scott D Berkowitz8, Keith A A Fox9, Manesh R Patel3. 1. Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina. Electronic address: matthew.sherwood@dm.duke.edu. 2. Janssen Pharmaceutical Research and Development, Raritan, New Jersey. 3. Division of Cardiovascular Medicine, Duke University Medical Center, Duke Clinical Research Institute, Durham, North Carolina. 4. Department of Medicine, Stanford University Medical Center, Stanford, California. 5. Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 6. Cardiovascular Institute, Mount Sinai Medical Center, New York, New York. 7. School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. 8. Bayer HealthCare Pharmaceuticals, Montville, New Jersey. 9. Department of Medicine, University of Edinburgh and Royal Infirmary of Edinburgh, Edinburgh, United Kingdom.
Abstract
BACKGROUND:Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. OBJECTIVES: This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of 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) trial. METHODS: The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. RESULTS:Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. CONCLUSIONS: In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation.
RCT Entities:
BACKGROUND: Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. OBJECTIVES: This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of 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) trial. METHODS: The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. RESULTS: Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. CONCLUSIONS: In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation.
Authors: Wayne A Ray; Cecilia P Chung; Katherine T Murray; Walter E Smalley; James R Daugherty; William D Dupont; C Michael Stein Journal: Gastroenterology Date: 2016-09-14 Impact factor: 22.682
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Authors: Benjamin A Steinberg; Nicholas G Ballew; Melissa A Greiner; Steven J Lippmann; Lesley H Curtis; Emily C O'Brien; Manesh R Patel; Jonathan P Piccini Journal: JACC Clin Electrophysiol Date: 2019-10-02