Sodium-Glucose Cotransporter-2 Inhibitors Therapy in Transthyretin Amyloid Cardiomyopathy: A Propensity-Matched Cohort Study

Background and Objectives: The evidence for sodium-glucose cotransporter-2 inhibitors (SGLT2i) in heart failure (HF) secondary to transthyretin amyloid cardiomyopathy (ATTR-CM) is limited. Evaluate the impact of SGLT2i on clinical outcomes in ATTR-CM. Methods: Single-center, retrospective cohort study of 111 patients with confirmed ATTR-CM between 2014 and 2023. Patients were categorized as SGLT2i-treated or untreated. Propensity score (PS) matching was performed based on 14 clinical variables, yielding 27 matched pairs (n=54). The primary outcome was all-cause mortality; secondary outcomes included HF hospitalization and a composite of mortality and HF hospitalization. Survival was analyzed using Kaplan-Meier estimates and Cox regression, with treatment modeled at baseline and as a time-varying covariate. Results: In the PS-matched cohort (n=54; mean age 81.4±4.3 years, 64.8% male), SGLT2i treatment was associated with lower all-cause mortality (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.13-0.85; p=0.021), the actuarial all-cause mortality rate was 9.3 versus 25.4 per 100 patient-years in untreated patients. Sensitivity analyses supported these findings (HR, 0.37; 95% CI, 0.15-0.93; p=0.034) and after covariate adjustment (HR, 0.35; 95% CI, 0.13-0.97; p=0.044). SGLT2i were linked to numerically fewer HF hospitalizations (HR, 0.39; 95% CI, 0.15-1.01; p=0.052) and a significantly lower composite of mortality and HF hospitalization (HR, 0.36; 95% CI, 0.15-0.88; p=0.025). SGLT2i were well tolerated, with a 7.4% drug discontinuation rate. Conclusions: In this study, SGLT2i treatment was associated with improved survival in ATTR-CM patients. While observational design and sample size limit causal inference, these findings support further evaluation of SGLT2i as adjunctive therapy in this population.