Abstract 14022: Effect of Discontinuation and Nonadherence to Oral Anticoagulants on Atrial Fibrillation Stroke Risk

Abstract

Introduction: Medicines don’t work in those who don’t take them. Although novel oral anticoagulants (NOACs) are more convenient than warfarin due to fewer drug-drug interactions and less need for laboratory monitoring, their considerable costs and lack of regular interactions with the healthcare system may also contribute to poor adherence. Little is known about the persistence and adherence in the era of NOACs, nor how such behaviors are associated with the risk of ischemic stroke and transient ischemic attack (TIA) among patients of varying baseline risk. Methods: We conducted a retrospective analysis using a large U.S. commercial insurance database, and identified 61,646 patients with atrial fibrillation who initiated one of OACs (warfarin, dabigatran, rivaroxaban and apixaban) between October 2010 and September 2014. We defined discontinuation as being off OACs for at least 3 months and adherence as the proportion of days covered of at least 80%. Cox proportional hazard models was used to examine whether the time that patients were off OACs, including both the gaps between medication fills and the time of discontinuation, increased the risk of ischemic stroke and TIA. Results: Approximately 1 in 3 patients discontinued OACs within one year after initiation and 1 in 10 switched to another OAC. The estimated likelihood of adherence was 0.77 during the time when patients were on their first-line medications. Apixaban had the highest continuation rate (65% at 1 year), while rivaroxaban had the best adherence (predicted probability of adherence 0.83). The event rate of stroke was 1.6 per 100 person years. Patients with high baseline risk (CHA2DS2-VASc ≥2) were more likely to have a stroke when they were off OACs for 1-3 months (HR=1.47, p<0.01), 3-6 months (HR=1.78, p<0.001) and ≥6 months (HR=2.16, p<0.001), compared to off OACs for less than a week. No significant effect was found among low-risk patients (CHA2DS2-VASc 0 or 1). Switching to another OAC was related to 22% increased risk of stroke (p=0.05). Conclusions: Despite their greater convenience relative to warfarin, discontinuation and nonadherence to NOACs is high. Lack of persistence and adherence was associated with increased risk of ischemic stroke and TIA among patients with elevated baseline risk.