The impact of glucagon-like peptide 1 agonists on anthracycline or human epidermal growth factor receptor 2 inhibitor-associated cardiotoxicity in patients with breast cancer and diabetes mellitus.
Cho‐Han Chiang, Yu‐Cheng Chang, Zhiting Tang, Xin Ya See, Kuan‐Yu Chi, Yu Chang, Cho Hung Chiang, Azin Ghamari, Lauren Mary Curtis, Tomas G. Neilan
Abstract
12026 Background: Anthracyclines or human epidermal growth factor receptor 2 (HER-2) inhibitors are associated with the potential for major adverse cardiovascular outcomes (MACE) among patients with breast cancer. Diabetes mellitus (DM) further increases the risk of MACE. Glucagon-like peptide 1 agonists (GLP1a) have been shown to improve MACE in the non-cancer population; however, there are no data testing whether GLP1a reduce the risk for MACE associated with anthracyclines or HER-2 inhibitors. Therefore, we hypothesized that GLP1a may decrease the risk for MACE among patients with breast cancer and DM receiving anthracycline or HER-2 inhibitors. Methods: We performed a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included adult breast cancer patients with type 2 DM who were treated with an anthracycline or HER-2 inhibitor therapy. We matched patients receiving a GLP1a with patients receiving non-GLP1a second-line diabetes medication based on the following variables: age, sex, pre-existing cardiac disease, the use of radiation, metastatic disease, cancer therapy, underlying comorbidities, and use of cardiovascular and diabetes medications. The primary outcome of interest, MACE, was defined as a composite of heart failure, myocardial infarction, and atrial fibrillation/flutter. Secondary outcomes included a composite of heart failure hospitalization and incident heart failure. Safety outcomes included all-cause mortality within 5 years of therapy initiation. Results: We matched 724 patients receiving a GLP1a treatment with patients receiving non-GLP1a treatment. The median age was 60 years for both cohorts. The prevalence of hypertension (81%), metastatic disease (61%), and radiation therapy (42%) was similar between cohorts, as was the use of anthracyclines and HER-2 inhibitors. In Cox proportional hazard analyses, the group receiving GLP1a treatment was associated with a lower risk of MACE (Hazard ratio (HR), 0.59 [95% CI: 0.41-0.86]), and heart failure hospitalization (HR, 0.56 [95% CI: 0.37-0.83]), and all-cause mortality (HR, 0.67 [95% CI: 0.48-0.93]) compared with non-GLP1a. Conclusions: GLP1a were associated with a reduction in major adverse cardiovascular events, incident heart failure and heart failure hospitalization, and all-cause mortality among anthracycline or HER-2 inhibitor-treated patients with breast cancer and DM. [Table: see text]