Incretin-based therapies cut mortality and inpatient visits in AF and HFpEF patients vs. SGLT2i

Patients with coexisting atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) face significantly increased morbidity and mortality. While both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and incretin-based therapies (including GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists like tirzepatide) have demonstrated cardiovascular benefits, their comparative effectiveness in this specific high-risk population remained undefined. Understanding which class offers superior outcomes is crucial for optimizing treatment strategies.

Researchers conducted a retrospective, propensity score-matched cohort study using the TriNetX Global Collaborative Network. They included adults diagnosed with AF or atrial flutter and HFpEF who initiated either incretin-based therapies (GLP-1 RAs or dual GLP-1/GIP RAs) or SGLT2i within 30 days of their qualifying diagnosis. A 1:1 matching process was performed based on baseline medications, demographics, and comorbidities, resulting in 7624 patients per cohort. Co-primary outcomes assessed at 1 year included all-cause mortality, inpatient visits, and emergency department (ED) visits. Secondary outcomes covered major adverse cardiovascular events (MACE) and AF-related procedures.

At 1 year, incretin-based therapy demonstrated significant advantages over SGLT2i in key outcomes.

All-cause mortality was 5.3% in the incretin group versus 7.3% in the SGLT2i group, representing a 27.9% reduction (HR 0.721, 95% CI 0.634-0.820; p < 0.001). Inpatient visits were also significantly lower with incretin-based therapies, occurring in 30.0% of patients compared to 37.4% in the SGLT2i group, a 25.7% reduction (HR 0.743, 95% CI 0.702-0.787; p < 0.001). However, there was no statistically significant difference in ED visits between the two groups (27.0% vs. 28.0%; HR 0.946, 95% CI 0.888-1.007; p = 0.081). Subgroup analyses for specific agents like semaglutide and tirzepatide were performed, though specific results were not detailed in the abstract.