Legacy effect of digital therapeutics on mortality in CHD patients treated with PCI: 8-year result of BAMA trial

Abstract Background The adherence to secondary prevention in coronary heart disease (CHD) patients is crucial but low. Digital therapeutics (DTx) using evidence-based, clinically evaluated, technology-based software algorithms or apps may be an efficient tool to optimize adherence. Our previous finding 1 showed short-term benefits of DTx on medication adherence among CHD patients after intervention therapy. Whether using such DTx during short period had clinical benefits persisting beyond active intervention, so-called legacy effects, remains unexplored. Purpose This study aims to assess the legacy effect of mobile app-based self-management DTx on long-term clinical outcomes. Methods The BAMA trial 1 was a parallel-designed, open-labeled, single-center, randomized controlled trial conducted during April 2016 and June 2018, randomized 300 CHD patients to DTx or traditional hospital-based follow-up care on a 1:1 ratio, and followed up for 1 year. The intervention and regular follow-up was finished in 2018 and participants could choose using the DTx or not afterwards. The DTx service was terminated in 2021 due to budget reasons. In this extended study of the BAMA trial, participants were followed up over 8 years after the randomization. The primary endpoint was the all-cause mortality and secondary endpoint was the cardiovascular mortality over 8 years. Kaplan-Meier curves and Cox analysis models were used to investigate the legacy effect of DTx. Results Among 290 patients included in the final analysis of BAMA trial, the primary and secondary endpoints, together with clinical data including lipid profile after the RCT during 8 years were collected among a total of 288 patients, and 2 (0.16%) were lost to follow-up. There were 142 (49.31%) and 146 (50.69%) patients from the DTx and control groups, respectively. Baseline characteristics were similar between the 2 groups. During 8 years, there were 22 (7.64%) deaths occurred , including 13 (4.51%) cardiovascular deaths among all participants. Even though all patients were quit from DTx intervention, those randomized to DTx group maintained significantly lower all-cause mortality (4.22% compared with 10.95% in control group; hazard ratio HR, 0.39; 95% confidence interval CI, 0.15 to 0.99; P=0.047) and cardiovascular mortality (1.41% vs. 7.53%; HR, 0.18; 95% CI, 0.04 to 0.83; P=0.028), even after adjust for clinical characteristics at 12-month during the initial trial period and mean LDL levels during follow-up, there was still a trend favored DTx on clinical outcomes including all-cause mortality (HR, 0.32; 95% CI, 0.08 to 1.23; P=0.097) and cardiovascular mortality (HR, 0.13; 95% CI, 0.01 to 1.19; P= 0.071). Conclusions A 12 months DTx treatment during the initial trial period was associated with a legacy benefit of improved survival over a 8 years post-trial follow-up. This underscores DTx potential to amplify long-term outcomes via early behavioral-metabolic modulation.Figure 1