Real-world efficacy of tirzepatide in patients with heart failure without diabetes.

BACKGROUND: Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown significant cardiovascular benefits in clinical trials. This study investigates the real-world impact of tirzepatide on heart failure (HF) outcomes, leveraging data from the TriNetX platform. METHODS: Using data from January 1, 2013, to December 01, 2024, we conducted a propensity-matched analysis of two cohorts of patients with HF without diabetes, where the only difference was the use of tirzepatide. The primary outcome was the incidence of acute heart failure (acute HF), with secondary outcomes including major adverse cardiovascular events (MACE), chronic kidney disease (CKD), stroke, and coronary arterial disease (CAD). RESULTS: After propensity-matching, 897 patients were compared between the two cohorts in a 4-year follow-up, showing that untreated patients were at higher risk of incident acute HF (HR: 3.12, 95 %CI = 2.240-4.349, log-rank p < 0.001) and MACE (HR: 3.57, 95 %CI = 2.32-5.48, log-rank p < 0.001). Stroke (HR: 2.796, 95 %CI = 1.353-5.776, log-rank p < 0.01), CKD (HR: 1.48, 95 %CI: 1.08-2.03, log-rank p = 0.015), and CAD (HR: 1.474, 95 %CI,1.169-1.859, log-rank p = 0.001) outcomes also favored the treatment cohort. CONCLUSION: Tirzepatide presents a promising therapeutic option for managing heart failure, with significant metabolic and cardiovascular benefits. These real-world findings reinforce its potential role as a transformative treatment in improving clinical outcomes and quality of life for patients with HF without diabetes.