Improved Survival With Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Patients With Heart Failure With Preserved Ejection Fraction and Metabolic Dysfunction-Associated Steatotic Liver Disease.
Adverse metabolic profile manifested as metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity affect the development and prognosis of heart failure (HF).
Whether treatments targeting metabolic derangements such as sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) are associated with improved outcomes patients with both HF and MASLD or obesity warrants investigation.
This retrospective study included 7 propensity score matched cohort analyses using deidentified electronic health record data from the TriNetX global health research network.
We evaluated the associations between MASLD, obesity, and the use of SGLT2 inhibitors or GLP-1 receptor agonists with adverse outcomes in patients with HF. Cohorts were defined based on combinations of comorbidities (HF subtype, MASLD, obesity, diabetes status) and medication exposure. Time-to-event outcomes with the Kaplain-Meier method and with Cox proportional hazards models for the calculation of hazard ratios (HRs) and 95% confidence intervals.
Among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction, MASLD was consistently linked to increased risk of nonfatal cardiovascular events, including HF (HR = 1.09, P < 0.001 and HR = 1.23, P < 0.001), myocardial infarction (HR = 1.03, P = 0.07 and HR = 1.08, P < 0.001), and stroke (HR = 1.04, P = 0.08 and HR = 1.07, P = 0.07). Use of SGLT2 inhibitors in HFpEF and MASLD patients with or without diabetes was associated with reduced all-cause mortality (HR = 0.76, P < 0.001 and HR = 0.69, P < 0.001) and major cardiovascular events. GLP-1 receptor agonists demonstrated a significant survival benefit (HR = 0.38, P < 0.001) in obese patients with HFpEF and MASLD without diabetes.
In patients with HFpEF, pharmacologic interventions targeting metabolic pathways demonstrate meaningful cardioprotective effects, especially in metabolically vulnerable subgroups.
Whether treatments targeting metabolic derangements such as sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) and glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists) are associated with improved outcomes patients with both HF and MASLD or obesity warrants investigation.
This retrospective study included 7 propensity score matched cohort analyses using deidentified electronic health record data from the TriNetX global health research network.
We evaluated the associations between MASLD, obesity, and the use of SGLT2 inhibitors or GLP-1 receptor agonists with adverse outcomes in patients with HF. Cohorts were defined based on combinations of comorbidities (HF subtype, MASLD, obesity, diabetes status) and medication exposure. Time-to-event outcomes with the Kaplain-Meier method and with Cox proportional hazards models for the calculation of hazard ratios (HRs) and 95% confidence intervals.
Among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction, MASLD was consistently linked to increased risk of nonfatal cardiovascular events, including HF (HR = 1.09, P < 0.001 and HR = 1.23, P < 0.001), myocardial infarction (HR = 1.03, P = 0.07 and HR = 1.08, P < 0.001), and stroke (HR = 1.04, P = 0.08 and HR = 1.07, P = 0.07). Use of SGLT2 inhibitors in HFpEF and MASLD patients with or without diabetes was associated with reduced all-cause mortality (HR = 0.76, P < 0.001 and HR = 0.69, P < 0.001) and major cardiovascular events. GLP-1 receptor agonists demonstrated a significant survival benefit (HR = 0.38, P < 0.001) in obese patients with HFpEF and MASLD without diabetes.
In patients with HFpEF, pharmacologic interventions targeting metabolic pathways demonstrate meaningful cardioprotective effects, especially in metabolically vulnerable subgroups.
Authors
Tepetes Tepetes, Filippatos Filippatos, Athanasopoulos Athanasopoulos, Konstantaki Konstantaki, Batziou Batziou, Soranidis Soranidis, Kostakou Kostakou, Stamatelopoulos Stamatelopoulos, Briasoulis Briasoulis
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