Lower-adherence direct oral anticoagulant use is associated with increased risk of thromboembolic events than warfarin

Background Real-world data have suggested inconsistent adherence to oral anticoagulation for thromboembolic event (TE) prevention in patients with Non valvular atrial fibrillation (NVAF), yet it remains unclear if event risk is elevated during gaps of non-adherence. Objective To compare difference in outcomes between direct oral anticoagulant (DOAC) and warfarin based on adherence to the therapy in patients with NVAF. Methods Using the MarketScan claims data, patients receiving prescription of warfarin or a DOAC for NVAF from January 2015 to June 2016 were included. Outcomes included hospitalization for TE (ischemic stroke or systemic embolism), hemorrhagic stroke, stroke of any kind, and major bleeding. Event rates were reported for warfarin and DOACs at a higher-adherence proportion of days covered (PDC > 80%) and lower-adherence (PDC 40–80%). Results The cohort included 83,168 patients prescribed warfarin (51% [ n = 42,639]) or DOAC (49% [ n = 40,529]). Lower adherence occurred in 36% ( n = 15,330) of patients prescribed warfarin and 26% ( n = 10,956) prescribed DOAC. As compared to higher-adherence warfarin after multivariable adjustment, the risk of TE was highest in lower-adherence DOAC (HR 1.26; 95% CI, 1.14–1.33), and lowest in higher-adherence DOAC (HR, 0.93; 95% CI, 0.88–0.99). There was a significantly higher risk of hemorrhagic stroke and stroke of any kind in the lower-adherence groups. Major bleeding was more common with lower-adherence DOAC (HR, 1.43, 95% CI, 1.35–1.52) and lower-adherence warfarin (HR, 1.32, 95% CI, 1.26–1.39). Conclusions In this large real-world study, low adherence DOAC was associated with higher risk of TE events as compared to high and low adherence warfarin.