Abstract 4369285: Lower Risk of Cardiovascular Events in Patients with Heart Failure Initiated on Semaglutide 2.4 mg in the Real-world: Results from the SCORE-HF Study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World – Heart Failure Population)

K Kim Smolderen (Yale University, New Haven, Connecticut, United States) C Carlos Mena-Hurtado (Department of Cardiovascular Medicine, Yale University, New Haven, CT) V Victoria Divino (Novo Nordisk Inc., Plainsboro, New Jersey, United States) Z Zhenxiang Zhao Y Yan Chen J Joanna Boland (Analysis Group, Inc., Los Angeles, California, United States) J Jinlin Song (Analysis Group, Inc., Los Angeles, California, United States) B Briain O Hartaigh (Novo Nordisk Inc., Plainsboro, New Jersey, United States) P Prashanth Iyer (Novo Nordisk Inc., Plainsboro, New Jersey, United States) F Filip Knop (Novo Nordisk A/S, Bagsværd, Denmark) M Michael Nanna (Yale School of Medicine, New Haven, Connecticut, United States)

Abstract

Background: In a prespecified analysis of the SELECT trial, semaglutide 2.4 mg reduced major adverse cardiovascular events (MACE) and heart failure (HF) composite outcomes in patients with established cardiovascular disease, overweight/obesity, and prevalent HF without diabetes. However, real-world evidence on the effectiveness of semaglutide 2.4 mg in reducing MACE and HF outcomes among patients with HF remains limited. Research Questions: To evaluate the associations between semaglutide 2.4 mg use and the risk of MACE and HF outcomes, respectively, among U.S. adults with overweight/obesity and HF but no diabetes in routine clinical practice using real-world data. Methods: Patients aged ≥45 years with overweight/obesity and HF but no diabetes were identified from a large claims database linked to clinical and laboratory data (Komodo Research Data). A propensity score model including 64 variables was used to match patients (1:2) who did and did not initiate semaglutide 2.4 mg (6/2021-12/2024). Hazard ratios for semaglutide 2.4 mg use vs. non-use were derived using Cox proportional hazards models for the revised 3-point MACE (myocardial infarction, stroke, and all-cause mortality), revised 5-point MACE (including revised 3-point MACE, hospitalization for HF, and coronary revascularization), 3-point MACE and 5-point MACE (replacing all-cause mortality with cardiovascular [CV]-related mortality), and 3-point HF outcome (hospitalization for HF, urgent visit for HF, and CV-related mortality). Results: After matching, 8,617 patients who initiated semaglutide 2.4 mg and 17,234 non-users were included; characteristics were well-balanced (standardized mean difference <0.1 for all). Compared with non-use, semaglutide 2.4 mg use was associated with a lower risk of revised 5-point MACE (hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.49 – 0.68), revised 3-point MACE (HR: 0.38, 95% CI: 0.28 – 0.50), 5-point MACE (HR: 0.61, 95% CI: 0.52 – 0.72), 3-point MACE (HR: 0.43, 95% CI: 0.31 – 0.58), and 3-point HF (HR: 0.65, 95% CI: 0.55 – 0.76) (all p < 0.001). Semaglutide 2.4 mg use was also associated with lower risk of MI, stroke, hospitalization for HF, all-cause mortality, and CV-related mortality, compared to non-use. Conclusion: In this real-world study of U.S. patients with overweight/obesity and HF but no diabetes, semaglutide 2.4 mg use was associated with significantly lower risks of MACE and HF outcomes.

Article Details

Journal Circulation
Volume / Issue Vol. 152, Issue Suppl_3
Published November 04, 2025
ISSN 0009-7322
Publisher Lippincott Williams & Wilkins

Journal Info

Circulation

Lippincott Williams & Wilkins

ISSN: 0009-7322 Health Sciences

Authors (11)

K

Kim Smolderen

Yale University, New Haven, Connecticut, United States

C

Carlos Mena-Hurtado

Department of Cardiovascular Medicine, Yale University, New Haven, CT

V

Victoria Divino

Novo Nordisk Inc., Plainsboro, New Jersey, United States

Z

Zhenxiang Zhao

Y

Yan Chen

J

Joanna Boland

Analysis Group, Inc., Los Angeles, California, United States

J

Jinlin Song

Analysis Group, Inc., Los Angeles, California, United States

B

Briain O Hartaigh

Novo Nordisk Inc., Plainsboro, New Jersey, United States

P

Prashanth Iyer

Novo Nordisk Inc., Plainsboro, New Jersey, United States

F

Filip Knop

Novo Nordisk A/S, Bagsværd, Denmark

M

Michael Nanna

Yale School of Medicine, New Haven, Connecticut, United States