Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction

Javed Butler; Steen Z. Abildstrøm; Barry A. Borlaug; Melanie J. Davies; Dalane W. Kitzman; Mark C. Petrie; Sanjiv J. Shah; Subodh Verma; Walter P. Abhayaratna; Vijay Chopra; Justin A. Ezekowitz; Michael Fu; Hiroshi Ito; Małgorzata Lelonek; Julio Núñez; Eduardo Perna; Morten Schou; Michele Senni; Peter van der Meer; Dirk von Lewinski; Dennis Wolf; Rebecca L. Altschul; Søren Rasmussen; Mikhail N. Kosiborod

doi:10.1016/j.jacc.2023.09.811

Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction

Javed Butler^*, Steen Z. Abildstrøm, Barry A. Borlaug, Melanie J. Davies, Dalane W. Kitzman, Mark C. Petrie, Sanjiv J. Shah, Subodh Verma, Walter P. Abhayaratna, Vijay Chopra, Justin A. Ezekowitz, Michael Fu, Hiroshi Ito, Małgorzata Lelonek, Julio Núñez, Eduardo Perna, Morten Schou, Michele Senni, Peter van der Meer, Dirk von LewinskiDennis Wolf, Rebecca L. Altschul, Søren Rasmussen, Mikhail N. Kosiborod^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

Abstract

Background: Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). Objectives: In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial. Methods: STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229). Results: At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF [ejection fraction] 45%-49%: 5.0 points [95% CI: −2.7 to 12.8 points], EF 50%-59%: 9.8 points [95% CI: 5.0 to 14.6 points], and EF ≥60%: 7.4 points [95% CI: 2.8 to 12.0 points]; P interaction = 0.56) and body weight (EF: 45%-49%: −7.6 [95% CI: −10.7 to −4.4], EF 50%-59%: −10.6 [95% CI: −12.6 to −8.6] and EF ≥60%: −11.9 [95% CI: −13.8 to −9.9]; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories. Conclusions: In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF.

Original language	English
Pages (from-to)	2087-2096
Number of pages	10
Journal	Journal of the American College of Cardiology
Volume	82
Issue number	22
DOIs	https://doi.org/10.1016/j.jacc.2023.09.811
Publication status	Published - 28 Nov 2023

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10.1016/j.jacc.2023.09.811

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Butler, J., Abildstrøm, S. Z., Borlaug, B. A., Davies, M. J., Kitzman, D. W., Petrie, M. C., Shah, S. J., Verma, S., Abhayaratna, W. P., Chopra, V., Ezekowitz, J. A., Fu, M., Ito, H., Lelonek, M., Núñez, J., Perna, E., Schou, M., Senni, M., van der Meer, P., ... Kosiborod, M. N. (2023). Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction. Journal of the American College of Cardiology, 82(22), 2087-2096. https://doi.org/10.1016/j.jacc.2023.09.811

@article{04615fbdc18e4b62898c4adb678b9bf0,

title = "Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction",

abstract = "Background: Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). Objectives: In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial. Methods: STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229). Results: At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF [ejection fraction] 45%-49%: 5.0 points [95% CI: −2.7 to 12.8 points], EF 50%-59%: 9.8 points [95% CI: 5.0 to 14.6 points], and EF ≥60%: 7.4 points [95% CI: 2.8 to 12.0 points]; P interaction = 0.56) and body weight (EF: 45%-49%: −7.6 [95% CI: −10.7 to −4.4], EF 50%-59%: −10.6 [95% CI: −12.6 to −8.6] and EF ≥60%: −11.9 [95% CI: −13.8 to −9.9]; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories. Conclusions: In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF.",

keywords = "GLP-1 receptor agonists, HFpEF, functional status, obesity, semaglutide, symptoms",

author = "Javed Butler and Abildstr{\o}m, {Steen Z.} and Borlaug, {Barry A.} and Davies, {Melanie J.} and Kitzman, {Dalane W.} and Petrie, {Mark C.} and Shah, {Sanjiv J.} and Subodh Verma and Abhayaratna, {Walter P.} and Vijay Chopra and Ezekowitz, {Justin A.} and Michael Fu and Hiroshi Ito and Ma{\l}gorzata Lelonek and Julio N{\'u}{\~n}ez and Eduardo Perna and Morten Schou and Michele Senni and {van der Meer}, Peter and {von Lewinski}, Dirk and Dennis Wolf and Altschul, {Rebecca L.} and S{\o}ren Rasmussen and Kosiborod, {Mikhail N.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = nov,

day = "28",

doi = "10.1016/j.jacc.2023.09.811",

language = "English",

volume = "82",

pages = "2087--2096",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Inc.",

number = "22",

}

Butler, J, Abildstrøm, SZ, Borlaug, BA, Davies, MJ, Kitzman, DW, Petrie, MC, Shah, SJ, Verma, S, Abhayaratna, WP, Chopra, V, Ezekowitz, JA, Fu, M, Ito, H, Lelonek, M, Núñez, J, Perna, E, Schou, M, Senni, M, van der Meer, P, von Lewinski, D, Wolf, D, Altschul, RL, Rasmussen, S & Kosiborod, MN 2023, 'Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction', Journal of the American College of Cardiology, vol. 82, no. 22, pp. 2087-2096. https://doi.org/10.1016/j.jacc.2023.09.811

TY - JOUR

T1 - Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction

AU - Butler, Javed

AU - Abildstrøm, Steen Z.

AU - Borlaug, Barry A.

AU - Davies, Melanie J.

AU - Kitzman, Dalane W.

AU - Petrie, Mark C.

AU - Shah, Sanjiv J.

AU - Verma, Subodh

AU - Abhayaratna, Walter P.

AU - Chopra, Vijay

AU - Ezekowitz, Justin A.

AU - Fu, Michael

AU - Ito, Hiroshi

AU - Lelonek, Małgorzata

AU - Núñez, Julio

AU - Perna, Eduardo

AU - Schou, Morten

AU - Senni, Michele

AU - van der Meer, Peter

AU - von Lewinski, Dirk

AU - Wolf, Dennis

AU - Altschul, Rebecca L.

AU - Rasmussen, Søren

AU - Kosiborod, Mikhail N.

PY - 2023/11/28

Y1 - 2023/11/28

N2 - Background: Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). Objectives: In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial. Methods: STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229). Results: At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF [ejection fraction] 45%-49%: 5.0 points [95% CI: −2.7 to 12.8 points], EF 50%-59%: 9.8 points [95% CI: 5.0 to 14.6 points], and EF ≥60%: 7.4 points [95% CI: 2.8 to 12.0 points]; P interaction = 0.56) and body weight (EF: 45%-49%: −7.6 [95% CI: −10.7 to −4.4], EF 50%-59%: −10.6 [95% CI: −12.6 to −8.6] and EF ≥60%: −11.9 [95% CI: −13.8 to −9.9]; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories. Conclusions: In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF.

AB - Background: Many therapies for heart failure (HF) have shown differential impact across the spectrum of left ventricular ejection fraction (LVEF). Objectives: In this prespecified analysis, the authors assessed the effects of semaglutide across the baseline LVEF strata in patients with the obesity phenotype of HF with preserved ejection fraction (HFpEF) in the STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF) trial. Methods: STEP-HFpEF randomized 529 patients (263 semaglutide; 266 placebo). For this prespecified analysis, patients were categorized into 3 groups based on LVEF: 45% to 49% (n = 85), 50% to 59% (n = 215), and ≥60% (n = 229). Results: At 52 weeks, semaglutide improved the dual primary endpoints of Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (estimated treatment difference: EF [ejection fraction] 45%-49%: 5.0 points [95% CI: −2.7 to 12.8 points], EF 50%-59%: 9.8 points [95% CI: 5.0 to 14.6 points], and EF ≥60%: 7.4 points [95% CI: 2.8 to 12.0 points]; P interaction = 0.56) and body weight (EF: 45%-49%: −7.6 [95% CI: −10.7 to −4.4], EF 50%-59%: −10.6 [95% CI: −12.6 to −8.6] and EF ≥60%: −11.9 [95% CI: −13.8 to −9.9]; P interaction = 0.08), to a similar extent across LVEF categories. Likewise, LVEF did not influence the benefit of semaglutide on confirmatory secondary endpoints: 6-minute walk distance (P interaction = 0.19), hierarchal composite endpoint (P interaction = 0.43), and high-sensitivity C-reactive protein (P interaction = 0.26); or exploratory endpoint of N-terminal pro-brain natriuretic peptide (P interaction = 0.96). Semaglutide was well-tolerated across LVEF categories. Conclusions: In patients with HFpEF and obesity, semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight to a similar extent across LVEF categories. These data support treatment with semaglutide in patients with the obesity phenotype of HFpEF regardless of LVEF.

KW - GLP-1 receptor agonists

KW - HFpEF

KW - functional status

KW - obesity

KW - semaglutide

KW - symptoms

UR - http://www.scopus.com/inward/record.url?scp=85176332284&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2023.09.811

DO - 10.1016/j.jacc.2023.09.811

M3 - Article

SN - 0735-1097

VL - 82

SP - 2087

EP - 2096

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 22

ER -

Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction

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