From bench to bedside: investigating SGLT2 inhibitors as a novel strategy against chemotherapy-induced cardiomyopathy
Abstract
Background: Anthracyclines are essential components of chemotherapeutic regimens for a broad spectrum of malignancies, yet their utility is constrained by cumulative, dose-dependent cardiotoxicity, often culminating in non-ischemic cardiomyopathy and heart failure. The pathogenesis involves oxidative stress, mitochondrial dysfunction, and topoisomerase IIβ-mediated DNA damage in cardiomyocytes. While ACE inhibitors and angiotensin receptor blockers (ARBs) have demonstrated modest cardioprotective effects, the efficacy of newer heart failure therapies remains underexplored. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, endorsed as Class I therapy for heart failure with reduced ejection fraction (HFrEF) per 2022 AHA/ACC/HFSA guidelines, have shown robust cardioprotective effects in large cardiovascular outcomes trials. However, their potential to prevent or attenuate anthracycline-induced cardiotoxicity has not been systematically evaluated. This study aimed to assess preclinical and clinical evidence supporting their use in anthracycline-exposed populations.
Methods: A systematic review was conducted by PRISMA 2020 guidelines. Comprehensive searches of major medical databases and clinical trial registries were performed through March 2025. Eligible studies investigated SGLT2 inhibitors, β-blockers, or ACE inhibitors in adult patients receiving anthracycline-based chemotherapy or in animal models replicating this exposure. Primary outcomes included changes in LVEF, GLS,…
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