Sex based differences in clinical outcomes among heart failure patients with cardiac amyloidosis on sodium glucose Co-transporter-2 inhibitor therapy: A propensity score–matched analysis

BACKGROUND Cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure (HF), and sex differences in the clinical outcomes of SGLT2i in HF patients with CA remain insufficiently studied. OBJECTIVE To study the sex related differences of SGLT2i among HF patients with CA. METHODS We used TriNetX to identify adults (≥18 years) with HF and CA on SGLT2i therapy from Jan 2021 to May 2025. Patients with end-stage renal disease (ESRD), chronic kidney disease (CKD) stage 5, atrial fibrillation/ atrial flutter (AF/AFL), type 1 diabetes mellitus (T1DM), or diabetic ketoacidosis (DKA) were excluded. The primary and secondary outcomes were compared between males and females in the overall sample and in subgroups stratified by HF phenotype. These groups were balanced by sex using a 1:1 propensity score matching. Cox regression and Kaplan-Meier curves assessed outcomes at 6 months and 3 years. RESULTS Among 1485 patients with CA+HF on SGLT2i, 34.7% were female. After matching, 478 patients (mean age 70±13 years) were identified in each group. No significant sex-based differences were found in mortality (HR 0.93; 95% CI 0.65-1.33), stroke, acute MI, incident AF, ESRD, or MACE. The risk of acute HF diagnosis at 6 months was also similar. However, among 271 matched HFpEF patients, females had a lower 3-year all-cause mortality rate compared to males (HR 0.54; 95% CI 0.32-0.90), while among 245 HFrEF patients, females had a higher 3-year all-cause mortality rate compared to males (HR 1.79; 95% CI 1.08-2.96). CONCLUSION Comparable outcomes were observed across sexes in HF+CA patients treated with SGLT2i. However, variable outcomes between sexes across the HF spectrum warrant further investigation.