Dapagliflozin to Prevent Anthracycline-Induced Cardiotoxicity

Anthracyclines, such as doxorubicin, are effective anticancer agents but may cause dose-dependent cardiac injury, including early changes in left ventricular function and cardiac biomarkers. Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor with established cardiovascular benefits in heart failure and potential cardioprotective effects beyond glucose lowering, including modulation of oxidative stress, inflammation, myocardial energetics and fibrotic remodeling. This randomized, double-blind, placebo-controlled phase 2 trial evaluated whether dapagliflozin attenuates early anthracycline-associated cardiac functional and biomarker changes in adults receiving anthracycline-based chemotherapy. A total of 94 participants were randomized in a 1:1 ratio to receive dapagliflozin 10 mg orally once daily plus standard anthracycline-based chemotherapy or matching placebo plus standard anthracycline-based chemotherapy for 4 months. Ninety participants completed the 4-month follow-up and were included in complete-case analyses. The primary echocardiographic outcome was change in left ventricular function from baseline to 4 months. Left ventricular systolic function was assessed using left ventricular ejection fraction (LVEF) as the principal systolic measure. Transmitral E/A ratio was analyzed as an exploratory filling index because it was consistently available across participants. Tissue Doppler indices and comprehensive diastolic dysfunction grading were not consistently available and were therefore not used for formal diastolic grading in the final analysis. Secondary outcomes included cardiac troponin I, NT-proBNP, galectin-3, CA 15-3, renal and hepatic function parameters, and adverse events. Echocardiography and laboratory biomarkers were assessed at baseline and 4 months, while adverse events were monitored continuously throughout the study period.

Inclusion Criteria: * Histologically confirmed breast cancer (or other cancers as relevant to the study). * Age 18-70 years. * Planned treatment with anthracycline-based chemotherapy * Normal kidney function, defined as serum creatinine 0.6-1.2 mg/dL. * Normal liver function, defined as ALT and AST 10-40 U/L. * Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. * Willingness to participate and provide written informed consent. Exclusion Criteria: * History of symptomatic heart failure (NYHA class III-IV) or prior anthracycline-related cardiac dysfunction. * Previous use of Dapagliflozin. * Pregnancy or breastfeeding. * Severe renal impairment (eGFR \< 30 mL/min/1.73m²). * Uncontrolled diabetes mellitus (HbA1c \> 9%). * Active or recurrent urinary tract infections (UTIs) within the last 6 months. * Known hypersensitivity to Dapagliflozin or related compounds. * Concurrent participation in another clinical trial investigating cardioprotective agents.