Tirzepatide and the prevention of heart failure in patients with obesity and atrial fibrillation: a multicenter real-world cohort study
H Wei, C C Yang, Y LinAbstract
Background
Both obesity and atrial fibrillation (AF) are strong, interrelated risk factors for developing heart failure (HF). Tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, has demonstrated favorable metabolic and cardiovascular effects, but its preventive role in HF among patients with combined obesity and AF remains uncertain.
Purpose
To investigate whether tirzepatide use is associated with a lower 1-year risk of new-onset HF in patients with obesity and AF.
Methods
Using the TriNetX global federated database, we identified adults with both obesity (BMI >30 kg/m²) and AF between January 2022 and June 2025. Patients prescribed tirzepatide were compared with matched controls without the drug. Propensity score matching (1:1) was applied to balance baseline characteristics. The primary outcome was new-onset HF; secondary outcomes included all-cause mortality and three-point major adverse cardiovascular events (MACE).
Results
After matching, 11,958 patients were included (5,979 per group). Tirzepatide use was associated with a significantly reduced risk of new-onset HF (HR 0.73; 95% CI 0.60–0.88; P = 0.0012), all-cause mortality (HR 0.25; 95% CI 0.16–0.39; P < 0.0001), and three-point MACE (HR 0.59; 95% CI 0.46–0.76; P < 0.0001). The associations were consistent across demographic and clinical subgroups.
Conclusions
In this large, real-world cohort of patients with obesity and AF, tirzepatide use was associated with a lower incidence of HF, mortality, and MACE within one year. These findings suggest tirzepatide may offer cardiovascular protection in this high-risk population, warranting confirmation in prospective studies.For image description, please refer to the figure legend and surrounding text.