Effects of a Pharmacist-Led Educational Interventional Program on Electronic Monitoring–assessed Adherence to Direct Oral Anticoagulants: A Randomized, Controlled Trial in Patients with Nonvalvular Atrial Fibrillation

PURPOSE: Several landmark trials have reported that direct oral anticoagulants (DOACs) are more effective in preventing stroke and systemic embolism than vitamin K antagonists. However, nonadherence to DOACs worsens prognosis in patients with nonvalvular atrial fibrillation (NVAF) despite the effectiveness of the drugs. The purpose of this study was to evaluate the effects of a pharmacist-led educational interventional program involving motivational interviewing on medication adherence, as assessed by electronic monitoring, in patients receiving DOACs for the treatment of NVAF. METHODS: This prospective, randomized, interventional study was conducted at outpatient cardiology clinics at general hospitals and pharmacies in Japan. Patients with NVAF who were treated with a once-daily DOAC (edoxaban) or a twice-daily DOAC (apixaban) were randomized to receive either: (1) an educational interventional program involving motivational interviewing regarding adherence to anticoagulants; or (2) standard medication counseling. The primary end point was the change in the medication adherence rate, calculated as the number of days that patients appropriately took the drug, as assessed by an electronic monitoring device, divided by the total number of days that the drug was prescribed, from a 12-week observation period to a 12-week intervention period. The secondary end points were tolerability outcomes. The effect of the educational interventional program on the primary end point was analyzed in subgroups stratified by gender and type of DOAC received. FINDINGS: A total of 268 patients completed the observation period and were randomly assigned to one of the two study groups. The difference in the primary end point between the educational interventional program group and the standard medication counseling group was not significant (mean [SD], 2.9% [7.5%] vs 3.4% [8.3%]). On multiple linear regression analysis, the difference in DOAC adherence between the two groups was not significant, but that adherence to apixaban was significantly improved among men in the educational interventional program (β = 0.219; P = 0.012). Two patients died of causes considered unrelated to treatment; no stroke/systemic embolism or major bleeding events were observed. IMPLICATIONS: In this randomized, controlled study of the effects of a pharmacist-led educational interventional program using motivational interviewing on adherence to DOACs among patients with NVAF, adherence to DOACs, as assessed using an electronic monitoring device, was not improved with the educational interventional program compared to standard medication counseling . However, adherence to twice-daily apixaban was improved among men, but not among women, in the educational interventional program group. In this study, the selection of DOACs was not randomized, and the lack of assessment of the association between adherence to DOACs and clinical outcomes was a limitation. Japan Registry of Clinical Trials (jRCT) indentifier: jRCTs031180142.