Trajectories of Oral Anticoagulation Adherence and Associated Clinical Outcomes During Long-Term Anticoagulation Among Medicare Beneficiaries With Venous Thromboembolism.

Background: Little is known about anticoagulation medication nonadherence patterns impacting effectiveness and safety outcomes in clinical practice.
Objective: We identified adherence trajectories of extended therapy with direct-acting oral anticoagulants (DOACs) and warfarin after 6 months initial anticoagulant therapy among Medicare beneficiaries with venous thromboembolism (VTE). We further assessed the associated recurrent VTE and major bleeding risks.
Methods: Using group-based trajectory models, this retrospective cohort study identified distinct beneficiary subgroups with similar adherence patterns of extended-phase anticoagulant treatment (DOACs or warfarin) for patients with VTE who completed 6 months of initial anticoagulant treatment. We examined associations between adherence trajectories and risks of recurrent VTE and major bleeding using inverse probability treatment weighted Cox proportional hazards models.
Results: Compared with no extended treatment, consistently high DOAC adherence was associated with decreased recurrent VTE risk (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.21-0.51) without increased major bleeding risk, and consistently high warfarin adherence was associated with decreased recurrent VTE risk (HR = 0.62, 95% CI = 0.40-0.95) and increased major bleeding risk (HR = 1.64, 95% CI = 1.12-2.41). Gradually declining adherence to DOACs (HR = 1.80, 95% CI = 1.07-3.03) or warfarin (HR = 2.34, 95% CI = 1.57-3.47) was associated with increased bleeding risk with no change in recurrent VTE risk.
Conclusion and Relevance: This real-world evidence suggests persistently adhering to extended DOAC therapy is associated with lower recurrent VTE risk without increasing major bleeding among Medicare beneficiaries with VTE. Persistently adhering to extended warfarin therapy was associated with lower recurrent VTE risk but higher major bleeding risk.
Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W-H L-C reported receiving research funding from Merck Sharp & Dohme Corp. E.D. reported receiving honorarium for training and education from Bristol Myers Squibb/Pfizer. C.D. is an employee of Sanofi S.A. and a stockholder of Portola Pharmaceuticals and reported receiving personal fees for being on the advisory board of Bristol Myers Squibb. This work was conducted when C.D. was affiliated with the University of Florida. No other disclosures were reported.