Safety and effectiveness of apixaban in comparison to warfarin in patients with nonvalvular atrial fibrillation: a propensity-matched analysis from Japanese administrative claims data

Abstract

Objective: To investigate the risk of bleeding events and stroke/systemic embolism (SE) among Japanese patients with nonvalvular atrial fibrillation (NVAF), focusing on the initial dosage of apixaban and patient age.

Methods: This retrospective cohort study used de-identified electronic health records based claims data from 314 acute-care hospitals in Japan. NVAF patients newly initiated on warfarin or apixaban, with no prescription during the 180-day blanking period, were eligible. Patients were allocated to receive warfarin or 5 or 2.5 mg twice daily (BID) apixaban. One-to-one propensity-score matching was used to balance patient characteristics between apixaban and warfarin.

Results: Among 31,006 eligible patients, 11,972 matched pairs were identified for apixaban versus warfarin. Mean age ± standard deviation was 77.7 ± 10.0 and 77.6 ± 10.0 years and CHADS₂ score was 2.2 ± 1.4 and 2.2 ± 1.4 for warfarin and apixaban, respectively. In the apixaban cohort, 39.4% of patients received the standard dose (5 mg BID) and 60.6% received the reduced dose (2.5 mg BID). Incidence rates (events per 100 person-years) of major bleeding, any bleeding and stroke/SE were 3.7, 23.1 and 3.1, and 2.5, 18.6 and 2.0 for warfarin and apixaban cohorts, respectively. Apixaban was associated with a significantly lower risk of any bleeding (hazard ratio [HR] 0.809, 95% confidence interval [CI] 0.731–0.895; p < .001), major bleeding (HR 0.655, 95% CI 0.505–0.849; p = .001) and stroke/SE (HR 0.637, 95% CI 0.478–0.850; p = .002).

Conclusions: Our observational data from clinical practice broadly confirms the safety and efficacy results of pivotal randomized controlled trials of apixaban for stroke prevention among NVAF patients.

Keywords:

• Bleeding
• novel oral anticoagulants
• nonvalvular atrial fibrillation
• apixaban
• warfarin
• stroke

Transparency

Declaration of funding

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

Author contributions: S.K. and Y.T. 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. K.S. was involved in designing the study, managing the project and interpreting the obtained results. J.K. was involved in designing the study, managing the project, interpreting the obtained results and drafting the manuscript.

Declaration of financial/other relationships

K.S. has disclosed that she is an employee of Bristol-Myers Squibb Co. J.K. has disclosed that he is an employee of Pfizer. S.K. and Y.T. have disclosed that they have served as consultants for BMS and Pfizer.

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 Shawn Li, Keith Friend and Wang Feng (Bristol-Myers Squibb Co.) and Aaron Jenkins (Pfizer Inc.) for their helpful advice and support throughout the study.