Association between oral anticoagulant adherence and serious clinical outcomes in patients with atrial fibrillation: A long-term retrospective cohort study

Background Patients with atrial fibrillation (AF) are frequently nonadherent to oral anticoagulants (OACs) prescribed for stroke and systemic embolism (SSE) prevention. We quantified the relationship between OAC adherence and AF clinical outcomes using methods not previously applied to this problem. Methods Retrospective observational cohort study of incident cases of AF from population-based administrative data over 23 years. The exposure of interest was proportion of days covered (PDC) during 90 days before an event or end of follow-up. Cox proportional hazard models were used to evaluate time to first SSE and the composite of SSE, TIA, or death, and several secondary outcomes. Results 44,172 patients were included with median follow-up of 6.7 years. For DOACs, each 10% decrease in adherence was associated with a 14% increased hazard of SSE and 5% increased hazard of SSE, TIA, or death. For VKA the corresponding increase in SSE hazard was 3%. Receiving DOAC or VKA was associated with primary outcome hazard reduction across most the PDC spectrum. Differences between VKA and DOAC were statistically significant for all efficacy outcomes and at most adherence levels. Conclusions Even small reductions in OAC adherence in patients with AF were associated with significant increases in risk of stroke, with greater magnitudes for DOAC than VKA. DOAC recipients may be more vulnerable than VKA recipients to increased risk of stroke and death even with small reductions in adherence. The worsening efficacy outcomes associated with decreasing adherence occurred without the benefit of major bleeding reduction.