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

Abstract

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.

Keywords:

• Bleeding
• novel oral anticoagulants
• nonvalvular atrial filtration
• apixaban
• dabigatran
• rivaroxaban
• warfarin

Transparency

Declaration of funding

This study was supported by Bristol-Myers Squibb Co. and Pfizer Inc.

Author contributions: S.K., Y.T. and F.W. were involved in designing the study, defining each disease and comorbid condition by ICD-10 codes, interpreting the obtained results and critically reviewing the drafted manuscript. T.M. was involved in preparing a statistical analysis plan and conducting the analysis. N.I. was involved in designing the study and managing the project. J.K. was involved in designing the study, managing the project, interpreting the obtained results and drafting the manuscript.

Declaration of financial/other relationships

F.W. has disclosed that he was an employee of BMS. N.I. and J.K. have disclosed that they were employees of Pfizer. S.K. and Y.T. have disclosed that they have served as consultants for BMS and Pfizer. T.M. has disclosed that he is an employee of Crecon Medical Assessment Inc. who received a payment from Pfizer in connection with the analysis.

CMRO peer reviewers on this manuscript have received an honorarium from CMRO for their review work, but have no relevant financial or other relationships to disclose.

Acknowledgements

The authors thank Ruslan Horblyuk, former employee of Pfizer Inc., for contributions to designing the study. We are also grateful to Makoto Kida (Bristol-Myers Squibb KK), Kiyomi Suwa (Pfizer Japan Inc.) and Fumiko Nakatsu (Pfizer Japan Inc.) for helpful advice and support throughout the study.