AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
SGLT2 Inhibitors and Major Adverse Cardiovascular Events in Chemotherapy-Related Cardiomyopathy: A Real-World Comparative Effectiveness Study
By Garg K, Agrawal A, Gandicheruvu H et al.
Introduction: Cancer therapy-related cardiac dysfunction (CTRCD) with HFrEF is a serious complication of cardiotoxic cancer therapies, and data on the effectiveness of SGLT2 inhibitors in this population are limited. We aimed to evaluate the association between SGLT2 inhibitor use and major adverse cardiovascular events (MACE) in patients with CTRCD and HFrEF using real-world data. Hypothesis: SGLT2i use is associated with reduced MACE and all-cause mortality in patients with cancer therapy-related HFrEF compared with non-users. Methods: Using the TriNetX U.S. Collaborative Network, we identified adults aged ≥18 with exposure to cardiotoxic antineoplastic agents (anthracyclines, trastuzumab, cyclophosphamide, bevacizumab, cisplatin, paclitaxel, sunitinib, sorafenib, fluorouracil, epirubicin, methotrexate) and subsequent systolic heart failure. Patients were stratified by GDMT regimen with versus without SGLT2i (empagliflozin or dapagliflozin) initiated after HFrEF diagnosis. Propensity score matching (1:1) balanced age, sex, race, hypertension, diabetes, obesity, tobacco use, dyslipidemia, chronic ischemic heart disease, and chronic kidney disease. The primary outcome was MACE (composite of cerebral infarction, acute myocardial infarction (AMI), and all-cause mortality). Individual components were assessed as secondary outcomes. Outcomes were evaluated at 1- and 5-year and Forest plots were generated. Results: After matching, 1,693 patients were included per cohort with well-balanced baseline characteristics (Figure 1). At 1 year, SGLT2i-based GDMT was associated with significantly lower MACE (hazard ratio (HR) 0.57; 95% confidence interval (CI) 0.48-0.67; p<0.001; Figure 2), driven primarily by reduced all-cause mortality (HR 0.50; 95% CI 0.43-0.58; p<0.001). Cerebral infarction (HR 0.89; 95% CI 0.57-1.42; p=0.634) and AMI (HR 0.76; 95% CI 0.54-1.06; p=0.107) did not reach statistical significance. At 5 years, MACE reduction persisted (HR 0.59; 95% CI 0.51-0.68; p<0.001; Figure 3), with sustained mortality benefit (HR 0.54; 95% CI 0.48-0.61; p<0.001). AMI was significantly less at 5 years (HR 0.76; 95% CI 0.57-0.99; p=0.045); cerebral infarction remained nonsignificant (HR 0.90; 95% CI 0.63-1.28; p=0.568). Conclusions: In this real-world cohort with cancer therapy-related HFrEF, SGLT2i-based GDMT was associated with a 43% relative reduction in MACE at 1 year and 41% at 5 years, driven predominantly by a 50% and 46% reduction in all-cause mortality, respectively. These findings provide real-world evidence supporting the integration of SGLT2i into the cardio-oncology treatment paradigm for CTRCD-related HFrEF.