Virtual Integrated Reliable Transformative User-driven E-health System for pacemakers and implantable cardioverter defibrillators

Background: Clinical burden of remote monitoring (RM) in cardiac implantable electronic devices (CIEDs) is high, yet uptake is variable. A digital health platform (VIRTUES) is posited to fill these gaps, with acceptable safety, efficacy and lower costs. Methods: VIRTUES-PM (V-PM) and VIRTUES-ICD (V-ICD) were multicenter, open-label, randomized controlled trials with blinded endpoint adjudication conducted in 13 Canadian centers for V-PM and 11 Canadian centers for V-ICD for patients with RM-eligible CIEDs. Allocation was 1:1 to standard of care (SOC) or VIRTUES care. In V-PM, there were two objectives: demonstration of non-inferiority of safety (time to major adverse cardiac or device-related hospitalizations) and superiority in cost; the secondary outcome was efficacy (time from clinical event to decision). In V-ICD, the first co-primary outcomes were safety and efficacy; cost was considered a second primary outcome. Analysis in each study used a sequential strategy of non-inferiority of the primary outcome, followed by superiority in cost. Outcome assessment was performed by blinded adjudication. Results: Between May 29, 2020 and February 28, 2025, 848 participants were randomized in V-PM (n=428 VIRTUES; n=420 SOC) and 1115 in V-ICD (n=526 VIRTUES; n=553 SOC). The mean age was 70±12 years; 34% were women in V-PM, and 65±12 years, 22% were women in V-ICD. Over a follow-up of 18 months, the safety outcome in V-PM occurred in 26 participants (6.1%) in the VIRTUES care arm, compared to 31 (7.4%) in SOC; hazard ratio 0.83; 95% CI (0.49, 1.39); p for non-inferiority=0.0213. Cost was lower by -$77 97% CI(-$100, -$54), p<0.01. In V-ICD, the safety outcome occurred in 62 (11.0%) in VIRTUES, and 62 (11.2%) in SOC, hazard ratio 0.98, 95% CI (0.69,1.39); p for non-inferiority 0.007. Efficacy was also non-inferior with time from clinical events to decision: median 2.0 interquartile range (0 to 15) in the VIRTUES care arm vs 1.00 IQR (0 to 8) days in the SOC arm (p =0.003 for non-inferiority). The second primary outcome of cost per participant was significantly lower in the VIRTUES care arm as compared with SOC (mean adjusted cost difference/participant -C$77; 95% CI (-$105, -$49); p<0.01. Conclusion: VIRTUES care was non-inferior to SOC for safety in patients with PMs and ICDs, as well as in efficacy in ICDs. In both trials, significant cost-savings were found. These two trials support the use of this technology for comprehensive CIED management. Trial Registration: VIRTUES PM NCT03636230 first posted August 17, 2018, VIRTUES ICD NCT03405740 first posted January 23, 2018.