(P20-025-25) Mortality and Heart Failure Exacerbations With Incretin-Mimetic Drugs for Weight Loss in Patients With Obesity-Related Heart Failure With Preserved Ejection Fraction

Objectives: Incretin-mimetic drugs for weight loss have shown promising results on quality of life, functional capacity, and risk for hospitalization for heart failure (HF) in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). The objective of this study was to determine whether differences exist between these agents on survival and the risk of HF exacerbation.

Methods: Retrospective study using the federated global research network, TriNetX. We included patients with obesity (UMLS:ICD10CM:E66.9), BMI (≥30 kg/m2) (UMLS:LNC:39156-5), diastolic (congestive) heart failure (UMLS:ICD10CM:I50.3), marker of HF severity Nt-proBNP (≥125 pg/mL) (UMLS:LNC:33762-6), either liraglutide (NLM:RXNORM:475968), semaglutide (NLM:RXNORM:1991302), or tirzepatide (NLM:RXNORM:2601723), and without diabetes (UMLS:ICD10CM:E08-E13). Primary outcomes: mortality and HF exacerbation (UMLS: ICD10CM:I50) over 365 days. After propensity score matching, we used Cox regression model, presented data as hazard ratios (HR), and used log-rank p-values.

Results: Compared to liraglutide, treatment with semaglutide (N=2,807) and tirzepatide (N=1,418) were associated with a lower risk of 1-year all-cause mortality (HR: 0.439, 95% CI: [0.356,0.541], p< 0.0001); and (HR: 0.309, 95% CI: [0.213,0.45], p< 0.0001), respectively, and were also associated with a lower risk of HF exacerbation (HR: 0.824, 95% CI: [0.774,0.876], p< 0.0001); and (HR: 0.747, 95% CI: [0.684,0.817], p< 0.0001), respectively. When semaglutide (N=1,052) and tirzepatide were compared (N=1,050), there was no significant difference on 1-year mortality (HR: 0.99, 95% CI: [0.617,1.587], p=0.9669) nor 1-year risk for HF exacerbation (HR: 0.904, 95% CI: [0.814, 1.005], p=0.0626).

Conclusions: Our results suggest semaglutide and tirzepatide may be superior to liraglutide in patients with obesity-related HFpEF. Moreover, we found no significant differences between semaglutide and tirzepatide with regard to 1-year all-cause mortality and risk for HF exacerbation. Future head-to-head randomized controlled studies comparing incretin-mimetic drugs in patients with obesity-related HfpEF are warranted.

Funding Sources: Virginia Commonwealth University