Abstract 4367825: Impact of SGLT2 Inhibitor Use on Cardiac Allograft Vasculopathy and Other Clinical Outcomes in Heart Transplant Recipients: A Propensity-Matched Real-World Study

Background: Cardiac allograft vasculopathy (CAV) and transplant rejection are major contributors to late morbidity and mortality following heart transplantation. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) offer cardiovascular benefits in various populations, but their safety and impact on heart transplant recipients remain poorly defined. Methods: Using the TriNetX Global Collaborative Network, which utilizes healthcare data from 144 healthcare institutions, we conducted a retrospective cohort study of adult heart transplant recipients. Exposure was defined as initiation of SGLT2i therapy within 5 years after transplant (canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin). Propensity score matching (1:1) was performed on 31 covariates including demographics, immunosuppressive agents, comorbidities, and baseline labs. Outcomes were analyzed using Kaplan-Meier and Cox proportional hazard models over a 3-year follow-up window. The primary outcome was CAV (T86.290); secondary outcomes included all-cause mortality, transplant rejection, and hospitalization. Results: After matching, 315 patients per group were included. Median follow-up was longer in the SGLT2 group (960 vs 733 days). CAV rates were similar in both groups (16.8% of SGLT2 users vs 12.1% of controls, HR 1.17, 95% CI: 0.76–1.80; p = 0.47). SGLT2i use was associated with significantly lower all-cause mortality (10.8% vs. 17.5%; HR 0.53, 95% CI: 0.34–0.81; p = 0.023), reduced hospitalizations (HR 0.58, 95% CI: 0.48–0.69; p < 0.001), and decreased rejection rates (HR 0.71, 95% CI: 0.56–0.90; p = 0.002). Conclusion: In this multicenter real-world cohort of heart transplant recipients, SGLT2 inhibitor use was associated with significantly reduced all-cause mortality, rejection and hospitalization, without an increase in transplant rejection. There was no significant increase in CAV. These findings support the potential role of SGLT2i as a safe adjunct in selected post-transplant patients.