Glucagon-like Peptide-1 Receptor Agonist in obeSE Heart Failure with Preserved Ejection Fraction with Type 2 Diabetes (PRAISE HFpEF DM)

Published Congress: HFA 2024

Dr. Elmas Kaplan

Background: Although the obesity phenotype is common in patients with heart failure with preserved ejection fraction (HFpEF), there is no specific treatment targeting obese patients with HFpEF. In the sTEP HFpEF DM study, semaglutide led to a significant reduction in heart failure-related symptoms and improvement in quality of life in obese patients with HFpEF and type 2 DM. The limited statistical power did not allow us to draw any conclusions about a possible reduction on cardiovascular mortality or hospitalisation for heart failure.

Objective: The aim of this study was to evaluate the effect of Glucagon-like Peptide-1 Receptor Agonist (GLP-1 RA) use on the composite outcome of hospitalisation for heart failure and all cause mortality in diabetic patients with HFpEF and obesity.

Methods: This is a multicentre observational cohort study involving 170 hospitals in the Veteran Affairs (VA) Healthcare System in the United States. The validated algorithm in the national VA electronic health record was used to define HFpEF. Patients with type 2 DM and HFpeF with BMI> 30/kg/m2 between January 2020 and December 2021 were screened. Exclusion criteria were HFpEF mimics and heart failure patients with improved ejection fraction. In this study with active comparator, new user design, patients were assigned to GLP-1 RA (treatment) and DPP4i/SU (comparator) arms.
The primary composite outcome was time to death from any cause or hospitalisation for heart failure.

Results: A total of 1024 patients were assigned to the GLP-1 RA arm and 796 to the DPP4i/SU arm. The mean age was 70.1/69.4 years and approximately 69 (3.7%) of the patients were female. Chronic renal failure, coronary artery disease, history of MI and peripheral arterial disease were more common in the GLP-1 RA arm, whereas hypertension was similar. BMI was 39.2 in the GLP-1 RA arm and 37.2 in the DPP4i/SU arm. GLP-1 RA use was associated with an approximately 20% reduction in the primary composite outcome compared with DPP4i (HR=0.80; IQ95% (0.67; 0.99); p=0.02).

Conclusion: In obese patients with heart failure with preserved LVEF, use of a GLP1 analogue as treatment for their diabetes seems to be associated with a reduction in the composite of hospitalisations for heart failure and all-cause mortality.

Interpretations: A total of 1,373,326 patients were screened, 1820 patients were included in the study, bias in patient selection? Although HFpEF is more common in women, only 3.7% of the patients included in the study were women. Despite the multicentre study design, its retrospective observational nature limits the generalisability of the results.  Obesity itself mimics HFpEF and one question that arises is whether patients may have been misclassified. The relationship with SGLT2-inh, which is indicated in patients with HFpEF, is one of the issues that needs to be investigated and the lack of documentation is one of the major limitations of this study.