Abstract 12196: Effect of Metformin on Heart Failure in Patients With Diabetes Mellitus Receiving Anthracycline Chemotherapy

Abstract

Introduction: The prevention of heart failure (HF) is an essential issue in patients treated with anthracyclines, however, existing treatments have demonstrated modest effects. Metformin (MET), widely used to treat diabetes, protects from anthracyclines-induced cardiotoxicity in vitro and in murine models. However, there is no research investigating the cardioprotective effects of MET in patients treated with anthracyclines. Hypothesis: MET is cardioprotective in patients treated with anthracyclines. Methods: Out of 5655 patients undergoing new anthracyclines therapy at a tertiary center between 2008-2021, 260 patients were treated with MET. The clinical characteristics associated with the use of MET were identified and a propensity-score (gender, diabetes, type of cancer, kidney and cerebrovascular disease) used to match 200 patients treated with MET to 200 patients without MET. The primary outcome was new-onset symptomatic HF defined by the AHA/ACC guidelines occurring within 1 year of the initiation of anthracyclines. Proportional hazard analysis was used to identify characteristics associated with HF. Results: Patients were 65 years old [57-70], 34% male. No differences were noted in age, cardiovascular risk factors, history, use of beta-blockers and ACE inhibitors between the MET and non MET groups. Six patients (3%) treated with MET and 20 matched patients (10%) developed HF within 1 year of anthracyclines initiation (P=0.004, Figure). Use of MET ([HR]: 0.27; 95% CI: 0.1 to 0.64; p = 0.002), use of insulin (HR: 2.27; 95% CI: 1.05 to 5; p = 0.04), coronary artery disease (HR: 4.69; 95% CI: 2.06 to 10.2; p < 0.001), and chronic kidney disease (HR: 2.65; 95% CI: 1.21 to 5.77 p = 0.02) were associated with incident HF. Conclusions: MET significantly reduced the risk for HF in patients treated with anthracyclines. Our findings are consistent with previous experimental studies and suggest a new therapeutic option in the prevention of cardiotoxicity.