Risk of stroke/systemic embolism, major bleeding and associated costs in non-valvular atrial fibrillation patients who initiated apixaban, dabigatran or rivaroxaban compared with warfarin in the United States Medicare population

Abstract

Objective: To compare the risk and cost of stroke/systemic embolism (SE) and major bleeding between each direct oral anticoagulant (DOAC) and warfarin among non-valvular atrial fibrillation (NVAF) patients.

Methods: Patients (≥65 years) initiating warfarin or DOACs (apixaban, rivaroxaban, and dabigatran) were selected from the Medicare database from 1 January 2013 to 31 December 2014. Patients initiating each DOAC were matched 1:1 to warfarin patients using propensity score matching to balance demographics and clinical characteristics. Cox proportional hazards models were used to estimate the risks of stroke/SE and major bleeding of each DOAC vs. warfarin. Two-part models were used to compare the stroke/SE- and major-bleeding-related medical costs between matched cohorts.

Results: Of the 186,132 eligible patients, 20,803 apixaban–warfarin pairs, 52,476 rivaroxaban–warfarin pairs, and 16,731 dabigatran–warfarin pairs were matched. Apixaban (hazard ratio [HR] = 0.40; 95% confidence interval [CI] 0.31, 0.53) and rivaroxaban (HR = 0.72; 95% CI 0.63, 0.83) were significantly associated with lower risk of stroke/SE compared to warfarin. Apixaban (HR = 0.51; 95% CI 0.44, 0.58) and dabigatran (HR = 0.79; 95% CI 0.69, 0.91) were significantly associated with lower risk of major bleeding; rivaroxaban (HR = 1.17; 95% CI 1.10, 1.26) was significantly associated with higher risk of major bleeding compared to warfarin. Compared to warfarin, apixaban ($63 vs. $131) and rivaroxaban ($93 vs. $139) had significantly lower stroke/SE-related medical costs; apixaban ($292 vs. $529) and dabigatran ($369 vs. $450) had significantly lower major bleeding-related medical costs.

Conclusions: Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.

Keywords:

• Warfarin
• stroke
• direct oral anticoagulants
• atrial fibrillation

Transparency

Declaration of funding

This work was funded by Pfizer Inc. and Bristol-Myers Squibb.

Declaration of financial/other relationships

A.A. has disclosed that he is an employee of University of California, Irvine, and was a paid consultant to Bristol-Myers Squibb in connection with this study and development of this manuscript. A.K., Q.Z. and O.B. have disclosed that they are employees of STATinMED Research, a paid consultant to Pfizer and Bristol-Myers Squibb in connection with this study and the development of this manuscript. J.T., O.D., J.M. and X.L. have disclosed that they are employees of Pfizer Inc., with ownership of stocks in Pfizer Inc. H.L., L.R. and L.V. have disclosed that they are employees of Bristol-Myers Squibb Company. L.R. and L.V. have disclosed that they have ownership of stocks in Bristol-Myers Squibb Company.

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

Michael Moriarty provided medical writing and editorial support with STATinMED Research which is a paid consultant to Bristol-Myers Squibb and Pfizer. Statistical programming for this study was provided by Yingchu Zhao and Yiyun Lin of STATinMED Research which is a paid consultant to Bristol-Myers Squibb and Pfizer.