Abstract 4142228: The Association Between Sodium-glucose Cotransporter-2 Inhibitors and Major Adverse Cardiac Events in Tafamidis-treated Transthyretin Amyloid Cardiomyopathy: A Real-World Analysis

Background: In patients with transthyretin amyloid cardiomyopathy (ATTR-CM), residual mortality remains high despite the use of tafamidis. Research Question: What is the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on tafamidis-treated ATTR-CM? Aims: We aimed to examine if SGLT2i were associated with additional benefits in this population. Methods: We conducted a retrospective, propensity score-matched cohort study using aggregate data from the TriNetX Global Collaborative Network database. We included adult patients with ATTR-CM, through the identification of tafamidis prescription, between May 1 st , 2019 and Nov 1 st , 2023. SGLT2i users were defined as having SGLT2i prescriptions on the day of tafamidis initiation. SGLT2i nonusers had no records of SGLT2i during the same period. Index date was set as the date of tafamidis initiation. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of any death, hospitalization for heart failure (HF), or cardiac arrest/ventricular tachycardia/fibrillation. Secondary endpoints were individual MACE. We set pneumonia and gastrointestinal bleeding as falsification endpoints. Differences in baseline characteristics between SGLT2i users and non-users were compared using standardized mean differences (SMDs) after propensity score matching. The outcomes were compared within 2 years of index date between SGLT2i users and non-users. Results: Of 4,995 tafamidis-treated ATTR-CM, 468 SGLT2i users were matched with 468 nonusers (mean age: 76.5 vs 76.3; females: 21.0% vs 18.5%; mean ejection fraction: 47.9% vs 47.8%). Important covariates were also balanced between two arms. The use of SGLT2i was associated with a significantly lower risk of MACE (HR, 0.72; 95% CI, 0.57 to 0.92), primarily driven by reductions in hospitalization for HF (HR, 0.69; 95% CI, 0.51 to 0.93) and all-cause mortality (HR, 0.70; 95% CI, 0.50 to 0.98) (Figure). There was no difference in prespecified falsification endpoints between two arms (Figure). Conclusions: In this retrospective database analysis, SGLT2i use in patients with tafamidis-treated ATTR-CM was associated with a significant reduction in MACE. This association warrants further investigation in prospective trials.