Efficacy, Safety, and Cost-effectiveness of 'Internet + Pharmacy Care' via the Alfalfa App in Warfarin Therapy Management After Cardiac Valve Replacement：A Randomized Controlled Trial (Preprint)

Anticoagulation management (AM) is important in preventing complications in patients undergoing cardiac valve replacement (CVR). The development of mobile applications offers new opportunities for the management of long-term anticoagulants. However, there is a lack of randomized controlled trials evaluating the effectiveness, safety, cost-effectiveness, and user demand for online AM. We aimed to evaluate the efficacy, safety, and cost-effectiveness of a 3-month warfarin dose adjustment mobile app-Alfalfa-compared to offline management in patients post-CVR. We also explored the app's feasibility on user satisfaction and demand. This study was a randomized controlled trial with assessments conducted at baseline and at a 3-month follow-up. Participants were eligible if they (1) had been on warfarin therapy for at least 3 months, (2) received warfarin management either through the Alfalfa app or via pharmacist-led anticoagulation outpatient clinic visits, (3) consented to regular follow-ups, (4) had not experienced serious bleeding or thrombotic events in the 3 months prior to warfarin treatment. A P value ≤.05 was considered statistically significant. A total of 405 participants were included in the analysis. The Time in Therapeutic Range (TTR) was significantly higher in the Alfalfa app group compared to the offline group (66.46% vs. 46.65%, P<.001). Participants in the Alfalfa app group had a higher monitoring frequency (8.14 vs. 4.47, P<. 001) and a greater percentage of international normalized ratio (INR) values within the target range (896/1660, 53.98% vs. 346/899, 38.49%; P<.001) than those in the offline group. Additionally, the Alfalfa app group exhibited lower rates of subtherapeutic (235/1660, 14.16% vs. 152/899, 16.91%; P<.05), and extreme subtherapeutic INR values (273/1660, 16.45% vs. 186/899, 20.69%; P<.05) compared to the offline group. However, the incidence of minor bleeding was higher in the Alfalfa app group (12/204, 5.9% vs. 3/201, 1.5%; P =.02). In terms of cost-effectiveness, the Alfalfa app group had a significantly lower average cost per test (42.37 vs. 78.3, P< .001), average time per test (47.42 vs. 90.74, P< .001), and cost-effectiveness ratio (C/E ratio: 385.90 vs. 662.90) compared to the offline group. A total of 86 participants completed the satisfaction questionnaire, and the vast majority of participants expressed high levels of satisfaction with the Alfalfa App, while also providing further suggestions for improvement. The integration of 'Internet + Pharmacy Care' using the Alfalfa App can improve the effectiveness of warfarin anticoagulation management in patients following heart valve surgery. The Alfalfa app provides a more efficient, secure, and cost-effective solution to warfarin management compared to traditional offline methods. Chinese Clinical Trial Registry, ChiCTR; ChiCTR1900021920; https://www.chictr.org.cn/showproj.html?proj=36832.