“Smart-Film” device to improve medication adherence to apixaban in patients with atrial fibrillation: a randomized controlled trial

Background Direct oral anticoagulants (DOACs) are the standard of care for reducing stroke risk in atrial fibrillation (AF). However, real-world data indicate that suboptimal adherence to DOACs increases stroke risk1-2. Previous adherence tools have yielded neutral results. We developed an internet-of-things “Smart-Film” device—a printed electronic circuit adhered to the back of a drug blister pack—connected via Bluetooth to the “Correctpill” smartphone app (Figure 1). Purpose To evaluate the impact of the “Smart-Film” device on adherence to twice-daily apixaban in patients with AF. Methods We conducted a parallel-group, randomized, open-label, blinded-endpoint trial to assess the effectiveness of the “Smart-Film” device in improving adherence to apixaban. Eligible patients were randomized to Smart-Film (SF) or standard care (SC). SF participants received the device, while SC participants received standard blister packs. The primary outcome was apixaban adherence rate, measured by pill counts at 6 and 12 weeks. Secondary outcome was plasma apixaban pharmacokinetic (PK) levels at 6 and 12 weeks. Clinical outcomes and bleeding events were tracked for 1 year. The target sample size was 170 patients (85 per group). Results Seventy-five participants were recruited between November 11, 2021, and November 21, 2023; 31 (41.3%) were randomized to SF and 44 (58.7%) to SC. The study was discontinued prematurely due to irreparable malfunction of the “Correctpill” app and Bluetooth transmission. Baseline demographics and clinical characteristics were depicted in Table 1. Adherence to apixaban was similar between SF and SC group at 6 weeks [SF: 99% (IQR 97.8-100) vs SC: 98.9% (IQR 95.2-100), p=0.534] and 12 weeks [SF: 98.9% (95.2-100) vs SC: 98.9% (95.2-100), p=0.991]. There was also no significant difference in plasma apixaban PK level between the SF and SC groups at 6 weeks [SF: 222.5ng/ml (155-290) vs SC: 208.5ng/ml (129-280), p=0.465] and 12 weeks [SF: 211.5ng/ml (128.5-347.5) vs SC: 236.5ng/ml (136.5-309), p=0.793]. At 1 year, only one patient from the SC group and non in the SF group had all-cause mortality (p=0.398). There was no cardiac mortality, ischemic stroke or hemorrhagic stroke observed at 1 year. Major bleeding (BARC ≥3) was not significant between the 2 groups (SF group: n=3, SC group: n=2, p=0.380). Conclusion The "Smart-Film" device did not improve adherence to twice-daily apixaban compared with standard care in patients with AF by measuring adherence rate and plasma apixaban PK level. Clinical outcomes, including mortality, stroke and bleeding, were comparable between groups at 1 year follow up. These findings highlight the challenges of leveraging digital health technologies to enhance medication adherence and underscore the need for more robust, reliable solutions in this space.