Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Cardiovascular Outcomes in Transthyretin Amyloid Cardiomyopathy

Abstract

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive form of heart failure characterized by restrictive hemodynamics and high morbidity. Tafamidis remains the only approved treatment, but its limited availability underscores the need for alternative therapies. Sodium-glucose co-transporter 2 inhibitors (SGLT2i), shown to improve outcomes in heart failure with preserved ejection fraction (HFpEF), may offer therapeutic benefits in ATTR-CM due to shared pathophysiological mechanisms. A retrospective cohort analysis was conducted using data from the TriNetX Global Research Network. Patients with wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) were divided into 2 groups: those receiving SGLT2i therapy and those not treated with SGLT2i. Propensity score matching balanced 19 baseline characteristics. Clinical outcomes, including heart failure exacerbations, all-cause hospitalizations, acute kidney injury (AKI), and all-cause mortality, were assessed over 5 years. The study included 623 matched patients in each cohort. SGLT2i therapy was associated with significant reductions in heart failure exacerbations (hazard ratio [HR] 0.64, 95% confidence interval [CI]: 0.48 to 0.86, p <0.01), all-cause hospitalizations (HR 0.72, 95% CI: 0.58 to 0.91, p <0.01), and AKI (HR 0.53, 95% CI: 0.35 to 0.79, p <0.01). A trend toward reduced all-cause mortality (HR 0.83, 95% CI: 0.63 to 1.08, p = 0.165) was observed, though not statistically significant. In conclusions, SGLT2 inhibitors demonstrate significant potential to reduce morbidity and healthcare utilization in wt-ATTR-CM patients, with promising trends toward improved survival. These findings highlight SGLT2i as a viable adjunct to existing therapies like tafamidis and warrant further investigation through prospective randomized trials.