Cardioprotective effectiveness of SGLT2 inhibitors in older diabetic women with early-stage breast cancer following anthracycline- and/or trastuzumab-based treatment.

Abstract

Background: Real-world evidence on protective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) against anthracycline- or trastuzumab-induced cardiotoxicity in patients with breast cancer is limited.

Objectives: To examine the cardioprotective benefits of SGLT2i in older women with early-stage breast cancer (EBC) following anthracycline- and/or trastuzumab-based therapies.

Design: This was a retrospective cohort study using the 2011-2019 SEER-Medicare database.

Methods: We identified women aged over 65.5 years and diagnosed with stage I-III BC who received anthracycline and/or trastuzumab and subsequently initiated antidiabetic medications. Propensity scores were used to match one new-user episode of SGLT2i with four new-user episodes of other antidiabetic medications (OAMs). The primary outcome was a composite endpoint consisting of heart failure (HF), stroke, myocardial infarction, and arrhythmia. Secondary outcomes included hospitalization due to HF (HHF) and incident HF or cardiomyopathy (CM). Cause-specific hazard ratios (csHR) between SGLT2i and OAMs groups were assessed for each outcome, with all-cause death treated as a competing event.

Results: From 1195 women examined, 1777 new-user episodes were identified. After 1:4 matching, there were 131 episodes in the SGLT2i group and 469 in the OAM group. Covariates were well-balanced between groups. No statistically significant differences were observed in the composite cardiovascular (csHR = 0.71; 95% confidence interval (CI): 0.44-1.15; p = 0.24), HHF (csHR = 0.92; 95% CI: 0.10-8.27; p = 0.94), or incident HF/CM (csHR = 0.77; 95% CI: 0.45-1.34; p = 0.36) outcomes. Results were consistent across individual SGLT2i and clinical subgroups, including those with/without established cardiovascular diseases and those exposed to various cardiotoxic cancer treatments.

Conclusion: No significant differences in cardiovascular risks were found between women with EBC who initiated SGLT2i versus OAMs after anthracycline or trastuzumab treatments, which might be due to the limited sample size. Further investigation through clinical trials is necessary to confirm the cardioprotective potential of SGLT2i among patients with EBC.