Cancer therapy–related cardiac dysfunction (CTRCD) is an increasing clinical problem as more patients receive potentially cardiotoxic antineoplastic agents. The role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in preventing CTRCD has not been well defined. This study used a large electronic health record network to assess whether exposure to GLP-1 RAs is associated with lower incidence of CTRCD and other cardiovascular outcomes among adults receiving cardiotoxic cancer therapy.
Investigators queried the TriNetX database for the period 2010 through 2023 to identify adults (≥18 years) with cancer who received cardiotoxic antineoplastic therapy and had no history of heart failure prior to the observation window. Exposure to GLP-1 RAs was ascertained from the EHR-derived dataset and patients were categorized into GLP-1 RA–exposed and unexposed groups. The analysis used Cox proportional hazards models to evaluate outcomes at 1 and 3 years.
From 711,091 eligible patients identified in TriNetX, 21,465 (3.0%) had documented exposure to GLP-1 RAs. The authors performed propensity score matching to balance baseline characteristics between exposed and unexposed groups. After matching, each cohort contained 19,803 patients. The matched population had a mean age of 65.8 ± 12.3 years and was 55.8% female. The most common malignancies in the matched cohorts were metastatic cancer and skin cancer.
The primary endpoint, CTRCD, was defined in this study as either new-onset heart failure or initiation of intravenous diuretic therapy. Time-to-event analyses used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) at 1 year and 3 years after index exposure. The abstract reports p values with statistical significance set at p < 0.01 for the primary comparisons presented.
In the propensity-matched cohorts, GLP-1 RA exposure was associated with a significantly reduced risk of CTRCD at both time points analyzed. At 1 year the hazard ratio for CTRCD was 0.49 (95% CI 0.45 to 0.54; p < 0.01). At 3 years the hazard ratio was 0.56 (95% CI 0.52 to 0.61; p < 0.01). The reported protective association was consistent across different classes of cardiotoxic antineoplastic therapy according to the abstract.
Beyond the primary CTRCD endpoint, GLP-1 RA use in the matched cohorts was associated with reductions in several cardiovascular and clinical outcomes. The abstract reports lower rates of incident heart failure, all-cause mortality, myocardial infarction, and atrial fibrillation among GLP-1 RA–exposed patients compared with matched unexposed patients. Exact event counts, absolute risk reductions, and numbers needed to treat are not provided in the abstract and would require review of the full text for detail.
Among patients with metastatic cancer, the study reports similar benefits associated with GLP-1 RA exposure. In this subgroup, GLP-1 RA use was associated with lower risks of CTRCD, reduced all-cause mortality, fewer atrial fibrillation events, fewer hospitalizations or emergency room visits, and less incident heart failure. The abstract does not provide subgroup sample sizes or detailed multivariable adjustment for this subgroup in the abstract text.
The abstract describes a large, observational, propensity-matched analysis from an EHR network showing that GLP-1 RA exposure is associated with a lower risk of CTRCD and several adverse cardiovascular outcomes in patients receiving cardiotoxic cancer therapy, including those with metastatic disease. As reported in the abstract, the findings are associations from an observational dataset using Cox models and propensity matching.
The abstract does not provide full details on covariates used for matching, timing and duration of GLP-1 RA exposure relative to cancer therapy, dosing, adjudication of outcomes, absolute event rates, or sensitivity analyses. Detailed methodology, potential residual confounding, and additional limitations are not reported in the abstract and would need to be assessed in the full-text article for clinical interpretation and application.
The abstract includes a declaration of competing interests. Multiple authors disclosed advisory roles, honoraria, research funding, stock or stock options, and travel support from a range of pharmaceutical and device companies. Specific disclosures listed in the abstract include advisory and consultancy relationships and research funding for several authors; full disclosure details are reported in the PubMed abstract.