Venous thromboembolism (VTE), constituting deep vein thrombosis (DVT) and pulmonary embolism (PE), is a common cause of vascular-related morbidity and mortality, resulting in a significant clinical and economic burden in the United States each year. Clinical guidelines recommend that patients with DVT and PE without cancer should be initiated on anticoagulation therapy with a direct oral anticoagulant over a vitamin K antagonist. Yet there is limited real-world evidence comparing the economic burden of warfarin and apixaban in treating VTE patients in a large commercially insured population.
To compare safety and effectiveness of warfarin and apixaban and evaluate associated economic burden in treating VTE patients in a large U.S. commercial health care claims database.
The PharMetrics Plus database was used to identify oral anticoagulant (OAC)-naive patients aged ≥ 18 years who initiated apixaban or warfarin within 30 days of a qualifying VTE encounter and had continuous health plan enrollment with medical and pharmacy benefits for 6 months before treatment initiation. Apixaban initiators and warfarin initiators were matched using the propensity score matching (PSM) technique. Cox proportional hazard models were used to assess and compare the risk of major bleeding (MB), clinically relevant nonmajor (CRNM) bleeding, and recurrent VTE. Generalized linear models were used to assess and compare the all-cause health care costs. A 2-part model with bootstrapping was used to evaluate MB- and recurrent VTE-related medical costs.
Among 25,193 prematched patients, 13,421 (53.3%) were prescribed warfarin and 11,772 (46.7%) were prescribed apixaban. After 1:1 PSM, 8,858 matched warfarin-apixaban pairs were selected with a mean follow-up of 109 days and 103 days, respectively. Warfarin was associated with a significantly higher risk of MB (HR = 1.52, 95% CI = 1.14-2.04), CRNM bleeding (HR = 1.27, 95% CI = 1.15-1.40), and recurrent VTE (HR = 1.50, 95% CI = 1.24-1.82) compared with apixaban. Warfarin patients had significantly higher all-cause medical costs per patient per month (PPPM; $2,333 vs. $1,992; = 0.001), MB-related costs PPPM ($112 vs. $65; = 0.020), and recurrent VTE-related costs PPPM ($287 vs. $206; = 0.014) compared with apixaban patients. Warfarin patients had similar all-cause total health care costs PPPM ($2,630 vs. $2,420; = 0.051) compared with apixaban patients.
Warfarin use was associated with a higher risk of MB, CRNM bleeding, and recurrent VTE compared with apixaban. Warfarin use was also associated with higher all-cause medical costs, MB-related medical costs, and recurrent VTE-related costs PPPM compared with apixaban. This study was funded by Bristol Myers Squibb and Pfizer, which were also involved in the study design, as well as writing and revising of the manuscript. Guo, Rajpura, Okano, and Rosenblatt are employees of Bristol Myers Squibb. Hlavacek, Mardekian, and Russ are employees of Pfizer. Keshishian, Sah, Delinger, and Mu are employees of SIMR, LLC, which received funding from the study sponsors to conduct this study.

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