A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants.
We aimed to evaluate bleeding risk in clinical practice in patients with atrial fibrillation (AF) being prescribed dabigatran, rivaroxaban, or apixaban compared with warfarin.



Using nationwide registries (Norwegian Patient Registry and Norwegian Prescription Database), we identified AF patients with a first prescription of oral anticoagulants between January 2013 and June 2015. Patients were followed until discontinuation or switching of oral anticoagulants, death, or end of follow-up. The primary endpoint was major or clinically relevant non-major (CRNM) bleeding.



In total 32 675 AF patients were identified (58% men, median age 74 years): 11 427 patients used warfarin, 7925 dabigatran, 6817 rivaroxaban, and 6506 apixaban. After a median follow-up of 173 days (25th, 75th percentile 84, 340), 2081 (6.37%) patients experienced a first major or CRNM bleeding. Using a Cox proportional hazard model adjusting for baseline characteristics, use of apixaban [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.61-0.80, P < 0.001] and dabigatran (HR 0.74, 95% CI 0.66-0.84, P < 0.001) were associated with a lower risk of major or CRNM bleeding compared with warfarin whereas use of rivaroxaban was not (HR: 1.05, 95% CI 0.94-1.17, P = 0.400). Use of dabigatran and rivaroxaban were associated with higher risk of gastrointestinal bleeding, whereas use of apixaban and dabigatran were associated with lower risk of intracranial bleeding, compared with warfarin.



In this nationwide cohort study in AF patients, apixaban and dabigatran were associated with a lower risk of major or CRNM bleeding compared with warfarin. The risk of gastrointestinal bleeding was higher with rivaroxaban and dabigatran compared with warfarin.
Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway sigrun.h@online.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Sigrun
S
Halvorsen
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Hematology, Østfold Hospital, Kalnes, Norway.
Waleed
W
Ghanima
Norwegian Computing Center, Oslo, Norway.
Ingunn
I
Fride Tvete
Bristol-Myers Squibb Norway AS, Oslo, Norway.
Cecilie
C
Hoxmark
Pfizer AS, Oslo, Norway.
Pål
P
Falck
Pfizer AS, Oslo, Norway.
Oddvar
O
Solli
HUNT Research Center, Faculty of Medicine, NTNU-Norwegian University of Science and Technology, Trondheim, Norway.
Christian
C
Jonasson
D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000150:complications*; D000069604:Dabigatran / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006470:Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D009664:Norway / Q000453:epidemiology; D055553:Prescription Drugs / Q000008:administration & dosage / Q000009:adverse effects*; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects; D011728:Pyridones / Q000008:administration & dosage / Q000009:adverse effects; D012042:Registries; D012189:Retrospective Studies; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate / Q000639:trends; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects
D000925:Anticoagulants; D055553:Prescription Drugs; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D014859:Warfarin; D000069552:Rivaroxaban; D000069604:Dabigatran
Apixaban; Atrial fibrillation; Bleeding; Dabigatran; Non-vitamin K antagonist oral anticoagulants; Oral anticoagulants; Rivaroxaban; Warfarin
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