Cardioprotective Potential of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Cancer Treated With Anthracyclines: An Observational Study

Abstract

Anthracyclines are pivotal in cancer treatment, yet their clinical utility is hindered by the risk of cardiotoxicity. Preclinical studies highlight the effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in mitigating anthracycline-induced cardiotoxicity. Nonetheless, the translation of these findings to clinical practice remains uncertain. This study aims to evaluate the safety and potential of SGLT2i for preventing cardiotoxicity in patients with cancer, without preexisting heart failure (HF), receiving anthracyclines therapy. Using the TriNetX Global Research Network, patients with cancer, without previous HF diagnosis, receiving anthracycline therapy were identified and classified into 2 groups based on SGLT2i usage. A 1:1 propensity score matching was used to control for baseline characteristics between the 2 groups. Patients were followed for 2 years. The primary end point was new-onset HF, and the secondary end points were HF exacerbation, new-onset arrhythmia, myocardial infarction, all-cause mortality, and all-cause hospitalization. Safety outcomes included acute renal failure and creatinine levels. A total of 79,074 patients were identified, and 1,412 were included post-matching (706 in each group). They comprised 53% females, 62% White, with a mean age of 62.5 ± 11.4 years. Over the 2-year follow-up period, patients on SGLT2i had lower rates of new-onset HF (hazard ratio 0.147, 95% confidence interval 0.073 to 0.294) and arrhythmia (hazard ratio 0.397, 95% confidence interval 0.227 to 0.692) compared with those not on SGLT2i. The incidence of all-cause mortality, myocardial infarction, all-cause hospitalization, and safety outcomes were similar between both groups. In conclusion, among patients with cancer receiving anthracycline therapy without preexisting HF, SGLT2i use demonstrates both safety and effectiveness in reducing anthracycline-induced cardiotoxicity, with a decreased incidence of new-onset HF, HF exacerbation, and arrhythmias.

Keywords: anthracyclines; cardiotoxicity; chemotherapy-related cardiotoxicity; prevention; sodium-glucose cotransporter-2 inhibitor.