Differences between patient-driven adherence to vitamin K antagonists and direct oral anticoagulants. Do few missed doses matter? ACO-MEMS Study

Abstract

Introduction: Lack of INR controls might affect the adherence to direct oral anticoagulants (DOAC). The vast majority of studies that addresses adherence to anticoagulants are retrospective and based on pharmacy refill data. Our aim was to compare the adherence between vitamin K antagonists (VKA) and DOAC and to analyze the clinical relevance of non-adherence.

Materials and methods: A prospective two-arm observational cohort study was performed in two Spanish public hospitals. Adherence was assessed by Medication Event Monitoring System. Relationship between adherence and events during follow-up and time in therapeutic range (TTR) in the VKA group were analyzed.

Results: 257 patients were included (132 DOAC and 125 VKA). Monitoring time was 120 days (101-133). Patients in VKA group showed higher taking adherence (97.9% vs. 95.8%) and less non-adherent patients of >5% and >10% of the doses, without differences in >20% of the doses. Taking adherence was strongly associated with TTR (AUC: 0.89, CI 95%: 0.81-0.97 of TTR for detection of non-adherent patients of >10% of doses). During a follow-up of 1.8 years (1.6-2) non-adherent patients of >5% of doses presented more thromboembolic events (HR 6.1, CI95% 1.3-28.1).

Conclusions: Although adherence to oral anticoagulant therapy was excellent, it was higher to VKA than to DOAC. Time in therapeutic range was highly sensitive to few missed doses of AVK. Non-adherence of >5% of prescribed doses had high clinical relevance.

Keywords: Anticoagulant drugs; Atrial fibrillation; INR; MEMS; Treatment adherence.