(VP042) EFFECTS OF ADHERENCE TO WARFARIN VS. DOACS ON ATRIAL FIBRILLATION OUTCOMES

Background: Medication nonadherence is common in AF patients prescribed oral anticoagulants (OACs) for stroke prevention. Nonadherence to direct OACs (DOACs) is a specific concern due to their short duration of action compared to warfarin. Effects of OAC adherence on clinical outcomes are uncertain because previous studies had short follow-up (usually 1 year), considered only two adherence states (adherent/nonadherent), and/or excluded warfarin users. Our objective was to compare the effects of nonadherence to warfarin vs. DOAC on AF-related clinical outcomes using adherence as a continuous variable.

METHODS AND RESULTS: This retrospective observational cohort study used linked population-based administrative data containing physician billing, hospitalization, and prescription records of 5 million British Columbians during 1996-2020 to identify incident cases of AF. The exposure of interest was proportion of days covered (PDC) for incident OAC prescriptions as a continuous time-updated variable. Primary outcomes were the composite of first stroke or systemic embolism (SSE), transient ischemic attack, or death, and time to first SSE. There were several secondary outcomes. Multivariable Cox proportional hazard models were used to evaluate associations between exposure and outcomes. OAC at time of event and its interaction with PDC within 90 days of event (or end of follow-up for those who did not have an event) was used to estimate the effects of OAC class. Contrast testing was used to compare warfarin and DOAC effects.

The study cohort included 34,946 patients (mean age 70.1, 45% female) with median follow-up of 6.7 years. Every 10% absolute increase in PDC was associated with a 4.1% (95%CI 2.8-5.3) and 9.3% (95%CI 7.0-11.5) decrease in hazard of SSE, TIA, or death for warfarin and DOAC users, respectively. For SSE, hazard reductions per 10% PDC increase were 18.4% (95%CI 16.4-20.3) and 25.5% (95%CI 22.0-28.9) for warfarin and DOAC, respectively. The effects of adherence and differences between warfarin and DOAC were statistically significant for all outcomes (p < 0.001 all contrast tests) except major bleeding. Effects of adherence on the primary outcomes were greater for all individual DOACs than warfarin, except dabigatran for SSE which was similar to warfarin.

Conclusion: Effects of adherence on outcomes were significantly greater with DOACs than warfarin, indicating DOAC recipients are more vulnerable to increased risk of stroke and death when nonadherent. Even small improvements in OAC adherence (i.e., 10%) were associated with significant risk reductions for stroke and death. The benefits of greater adherence accrued without an offsetting risk of major bleeding for both OAC classes.