Effect of Adherence to Oral Anticoagulants on Risk of Stroke and Major Bleeding Among Patients With Atrial Fibrillation

<jats:sec xml:lang="en"> <jats:title>Background</jats:title> <jats:p xml:lang="en"> In comparison to warfarin, non–vitamin K antagonist oral anticoagulants ( <jats:styled-content style="fixed-case">NOAC</jats:styled-content> s) have the advantages of ease of dosing, fewer drug interactions, and lack of need for ongoing monitoring. We sought to evaluate whether these advantages translate to improved adherence and whether adherence is associated with improved outcomes in patients with atrial fibrillation. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Methods and Results</jats:title> <jats:p xml:lang="en"> We performed a retrospective cohort analysis by using a large <jats:styled-content style="fixed-case">US</jats:styled-content> commercial insurance database to identify 64 661 patients with atrial fibrillation who initiated warfarin, dabigatran, rivaroxaban, or apixaban treatment between November 1, 2010, and December 31, 2014. During a median of 1.1 y of follow‐up, 47.5% of <jats:styled-content style="fixed-case">NOAC</jats:styled-content> patients had a proportion of days covered of ≥80%, compared with 40.2% in warfarin patients ( <jats:italic>P</jats:italic> <0.001). Patients with <jats:styled-content style="fixed-case">CHA</jats:styled-content> <jats:sub>2</jats:sub> <jats:styled-content style="fixed-case">DS</jats:styled-content> <jats:sub>2</jats:sub> ‐ <jats:styled-content style="fixed-case">VAS</jats:styled-content> c (risk based on the presence of congestive heart failure, hypertension age 65–74 y, age ≥75 y, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, sex category) score ≥4 were at increased risk of stroke when they were not taking anticoagulation ≥1 month versus <1 week (1–3 months: hazard ratio [ <jats:styled-content style="fixed-case">HR</jats:styled-content> ] 1.96, 3–6 months: <jats:styled-content style="fixed-case">HR</jats:styled-content> 2.64, ≥6 months: <jats:styled-content style="fixed-case">HR</jats:styled-content> 3.66; all <jats:italic>P</jats:italic> <0.001). Patients with <jats:styled-content style="fixed-case">CHA</jats:styled-content> <jats:sub>2</jats:sub> <jats:styled-content style="fixed-case">DS</jats:styled-content> <jats:sub>2</jats:sub> ‐ <jats:styled-content style="fixed-case">VAS</jats:styled-content> c score 2 or 3 were at increased risk of stroke when they were not taking anticoagulation ≥6 months ( <jats:styled-content style="fixed-case">HR</jats:styled-content> 2.73, <jats:italic>P</jats:italic> <0.001). In these patients with <jats:styled-content style="fixed-case">CHA</jats:styled-content> <jats:sub>2</jats:sub> <jats:styled-content style="fixed-case">DS</jats:styled-content> <jats:sub>2</jats:sub> ‐ <jats:styled-content style="fixed-case">VAS</jats:styled-content> c score ≥2, nonadherence was not associated with intracranial hemorrhage. Among patients with <jats:styled-content style="fixed-case">CHA</jats:styled-content> <jats:sub>2</jats:sub> <jats:styled-content style="fixed-case">DS</jats:styled-content> <jats:sub>2</jats:sub> ‐ <jats:styled-content style="fixed-case">VAS</jats:styled-content> c score 0 or 1, time not taking anticoagulation was not associated with stroke, but not taking anticoagulation ≥3 months was associated with a significant reduction of bleeding. </jats:p> </jats:sec> <jats:sec xml:lang="en"> <jats:title>Conclusions</jats:title> <jats:p xml:lang="en"> Adherence to anticoagulation is poor in practice and may be modestly improved with <jats:styled-content style="fixed-case">NOAC</jats:styled-content> s. Adherence to therapy appears to be most important in patients with <jats:styled-content style="fixed-case">CHA</jats:styled-content> <jats:sub>2</jats:sub> <jats:styled-content style="fixed-case">DS</jats:styled-content> <jats:sub>2</jats:sub> ‐ <jats:styled-content style="fixed-case">VAS</jats:styled-content> c score ≥2, whereas the benefits of anticoagulation may not outweigh the harms in patients with <jats:styled-content style="fixed-case">CHA</jats:styled-content> <jats:sub>2</jats:sub> <jats:styled-content style="fixed-case">DS</jats:styled-content> <jats:sub>2</jats:sub> ‐ <jats:styled-content style="fixed-case">VAS</jats:styled-content> c score 0 or 1. </jats:p> </jats:sec>