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

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 co-transporter-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 cancer patients, without pre-existing heart failure (HF), receiving anthracyclines therapy. Using the TriNetX Global Research Network, cancer patients without prior HF diagnosis, receiving anthracycline therapy were identified and classified into two groups based on SGLT2i usage. A 1:1 propensity score matching was used to control for baseline characteristics between the two groups. Patients were followed for 2 years. The primary endpoint was new-onset HF and secondary endpoints 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 (HR 0.147, 95% CI [0.073 - 0.294]) and arrhythmia (HR 0.397, 95% CI [0.227 - 0.692]) compared to 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, amidst cancer patients 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.