Oral anticoagulation therapy and subsequent risk of venous thromboembolism in atrial fibrillation patients

Abstract

Objective: Oral anticoagulation (OAC) prescribed to AF patients for the prevention of cardioembolic complications likely has the added benefit of preventing venous thromboembolism (VTE). This study evaluated, among AF patients who are anticoagulated, whether type of OAC was associated with subsequent VTE risk.

Methods: Non-valvular AF patients prescribed OACs between 2010 and September 2015 were identified via the MarketScan administrative claims databases. OACs included warfarin and direct OACs (DOACs: dabigatran, rivaroxaban, and apixaban). Incident VTE was defined by ICD-9-CM codes. Patients were matched on age, sex, CHA₂DS₂-VASc, and high-dimensional propensity scores. The final analysis included 117,912 AF patients.

Results: In total, 1357 VTE events accrued over a mean follow-up of 484 days. In multivariable-adjusted, propensity score-matched Cox models, relative to new users of warfarin, risk of incident VTE was lower among new users of dabigatran [hazard ratio (95% confidence interval) = 0.55 (0.47–0.66)] and apixaban [0.51 (0.39–0.68)], but similar among new users of rivaroxaban [1.01 (0.87–1.19)]. In head-to-head DOAC comparisons, VTE risk was lower among users of dabigatran [0.48 (0.36–0.64)] and apixaban [0.61 (0.47–0.78)] vs rivaroxaban. Findings were mostly similar across patient sub-groups.

Conclusions: In this large practice-based population of AF patients prescribed OACs for primary prevention of stroke and systemic embolization, subsequent risk of VTE was lowest among those prescribed apixaban and dabigatran, while risk was similar with prescriptions for warfarin and rivaroxaban. Among AF patients prescribed OACs, lowering the risk of VTE may be an additional benefit of apixaban and dabigatran, beyond the reduced bleeding risk observed in randomized clinical trials.

Keywords:

• Anticoagulation
• Atrial fibrillation
• Venous thromboembolism
• Comparative effectiveness

Transparency

Declaration of funding

This work was supported by NIH National Heart Lung and Blood Institute grants R01-HL122200 and R01-HL131579 and American Heart Association grant 16EIA26410001 (Alonso). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Declaration of financial/other relationships

No relationships to declare. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

No assistance in the preparation of this article is to be declared.