Bleeding risk of apixaban, dabigatran, and low-dose rivaroxaban compared with warfarin in Japanese patients with non-valvular atrial fibrillation: a propensity matched analysis of administrative claims data.
OBJECTIVES
There is scarce evidence comparing novel oral anticoagulants (NOACs) with warfarin in real-world settings in Japan. This study compared the risk of bleeding events among patients with non-valvular atrial fibrillation (NVAF) initiating treatment with NOACs versus warfarin.


METHODS
A retrospective cohort study was conducted using a de-identified electronic health record based database of health claims and Diagnosis Procedure Combination data from 275 consenting hospitals in Japan. NVAF patients newly initiated on oral anticoagulants were eligible. Based on the first prescription, patients were assigned to 5/2.5 mg BID apixaban, 150/110 mg BID dabigatran, 15/10 mg QD rivaroxaban (approved dose lower in Japan compared to Western countries [20/15 mg QD]) or warfarin groups. One-to-one propensity score matching (PSM) was used to balance patient characteristics between warfarin and each NOAC. Patients were followed up to 1 year post-first prescription.


RESULTS
Among 38,662 eligible patients, a total of 5977, 5090, and 6726 matched pairs were identified for warfarin versus apixaban, warfarin versus dabigatran, and warfarin versus rivaroxaban, respectively after PSM. Compared to warfarin, apixaban (hazard ratio [HR] 0.586; 95% CI 0.421-0.815), dabigatran (HR 0.617; 0.425-0.895) and rivaroxaban (HR 0.693; 0.514-0.933) were associated with a significantly lower risk of major bleeding. The risk of any bleeding was significantly lower for apixaban (HR 0.782; 0.682-0.896), but not for dabigatran (HR 0.988; 0.860-1.135) or rivaroxaban (HR 0.938; 0.832-1.057) when comparing to warfarin.


CONCLUSIONS
Among Japanese patients with NVAF, treatment with apixaban 5/2.5 mg BID was associated with a significantly lower risk of major bleeding and any bleeding when compared to warfarin. Treatment with dabigatran 150/110 mg BID or rivaroxaban 15/10 mg QD was associated with a significantly lower risk of major bleeding, but not any bleeding, than warfarin. The potential benefit of individual NOACs in real-world practice needs to be assessed further.
['Kohsaka|Shun|S|', 'Murata|Tatsunori|T|', 'Izumi|Naoko|N|', 'Katada|Jun|J|', 'Wang|Feng|F|', 'Terayama|Yasuo|Y|']
D000368:Aged D000369:Aged, 80 and over D000925:Anticoagulants D001281:Atrial Fibrillation D015331:Cohort Studies D000069604:Dabigatran D005260:Female D006470:Hemorrhage D006801:Humans D007564:Japan D008297:Male D008875:Middle Aged D057216:Propensity Score D016016:Proportional Hazards Models D011720:Pyrazoles D011728:Pyridones D012189:Retrospective Studies D012306:Risk D000069552:Rivaroxaban D014859:Warfarin
Bleeding apixaban dabigatran rivaroxaban warfarin novel oral anticoagulants nonvalvular atrial filtration