GLP-1 Receptor Agonists and Primary Prevention of Cancer Therapy-Related Cardiac Dysfunction

Cancer therapy-related cardiac dysfunction (CTRCD) is becoming more prevalent, while the role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in mitigating CTRCD remains uncertain. We assessed the association between GLP-1 RA and CTRCD in cancer patients using the TriNetX database (2010-2023), identifying adult cancer patients (≥18 years) without prior heart failure (HF) who were receiving cardiotoxic antineoplastic therapy. Patients were stratified into GLP-1 RA-exposed and unexposed groups, and the primary outcome was CTRCD, defined as new-onset HF or intravenous diuretic initiation. Cox proportional hazard models were used to evaluate outcomes at 1 and 3 years. Among 711,271 eligible patients, 21,465 (3.0%) received GLP-1 RAs. After propensity score matching, each cohort included 19,803 patients (mean age: 65.8 ± 12.3 years; 55.8% women), with metastatic cancer and skin cancer being the most common malignancies. GLP-1 RA exposure was associated with a significantly reduced risk of CTRCD at 1 year (HR: 0.49, 95% CI: 0.45-0.54, p < 0.01) and 3 years (HR: 0.56, 95% CI: 0.52-0.61, p < 0.01), with consistent effects across different cardiotoxic therapies. GLP-1 RA use was also associated with reductions in incident HF, all-cause mortality, myocardial infarction, and atrial fibrillation. In patients with metastatic cancer, similar benefits were observed, including lower risks of CTRCD, all-cause mortality, atrial fibrillation, hospitalizations or emergency room visits, and incident HF. Overall, GLP-1 RA use was associated with a lower risk of CTRCD and cardiovascular events in cancer patients receiving cardiotoxic antineoplastic therapy, including those with metastatic disease.