Aims: To investigate the association between adherence to non-vitamin K antagonist oral anticoagulant (NOAC) and clinical outcomes and to determine the optimal cut-off level of NOAC adherence among patients with atrial fibrillation (AF). Methods and results: Using the Korean National Health Insurance Service database, we identified 96 197 patients with non-valvular AF who initiated NOAC or warfarin in 2013-16. We compared clinical outcomes between adherent [proportion of days covered (PDC) ≥80%] vs. non-adherent (PDC <80%) NOAC users, and further with warfarin users. We assessed the outcomes according to different levels of adherence. The proportion of adherent NOAC users was 64.0%. Compared with non-adherent NOAC users, adherent NOAC users were at lower risks of ischaemic stroke/systemic embolism (SE) [adjusted hazard ratio (aHR) 0.73, 95% confidence interval (CI) 0.69-0.79], and myocardial infarction (aHR 0.82, 95% CI 0.72-0.93), whereas there was no significant risk alteration for major bleeding (aHR 1.01, 95% CI 0.91-1.11). Compared with warfarin, non-adherent NOAC use failed to have better efficacy against ischaemic stroke/SE (aHR 0.99, 95% CI 0.93-1.05) and rather had increased risk of myocardial infarction (aHR 1.13, 95% CI 1.03-1.25). In NOAC users, the risks of adverse outcomes decreased according to gradual increase of adherence rates with the lowest risks in ≥90%, except for major bleeding in which there were no significant associations. Conclusions: In an adherence level-dependent fashion, adherent use of NOAC showed better clinical outcomes without increasing bleeding risk. Maintaining ≥90% of adherence optimizes effectiveness of NOAC therapy without compromising its safety.
Bibliographical noteFunding Information:
Conflict of interest: G.Y.H.L. has served as a consultant for Bayer/ Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo, and as a speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo; no fees were directly received personally. B.J. has served as a speaker for Bayer, BMS/Pfizer, Medtronic, and Daiichi-Sankyo, and has received research funding from Medtronic and Abbott; no fees were directly received personally. And all other authors have no conflict of interest to declare.
This work was supported by a research grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology [grant number NRF-2017R1A2B3003303] and grants from the Korean Healthcare Technology R&D project funded by the Ministry of Health & Welfare [grant numbers HI16C0058, HI15C1200].
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)