Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program

Schou, M; Petrie, MC; Borlaug, BA; Butler, J; Davies, MJ; Kitzman, DW; Shah, SJ; Verma, S; Patel, S; Chinnakondepalli, KM; Harring, S; Abildstrøm, SZ; Liisberg, K; Kosiborod, MN; STEP-HFpEF Trial Committees and Investigators

doi:10.1016/j.jacc.2024.04.038

Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program

J Am Coll CardiolPublished 23 Jun 2024Prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials

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Authors' conclusion

In patients with obesity-related HFpEF, fewer semaglutide-treated than placebo-treated patients had a deterioration, and more had an improvement, in NYHA functional class at 52 weeks.

Study context

Population: Patients with obesity-related heart failure with preserved ejection fraction (HFpEF)
Participants: 1,145 patients · 2 RCTs

Comparison: Semaglutide 2.4 mg once weekly vs placebo
Outcome: Change in NYHA functional class
Follow-up: Baseline to 52 weeks

Methodological detailspooled data from 2 international randomised trials, double-blind

Pooled data from 2 international randomised trials
Double-blind

Pooled result

As reported in the abstract

NYHA functional class · 52 weeks

Semaglutide

Improvement: 32.6%
Deterioration: 2.09%

Placebo

Improvement: 21.5%
Deterioration: 5.24%

Improvement

Semaglutide32.6%

Placebo21.5%

Deterioration

Semaglutide2.09%

Placebo5.24%

Semaglutide vs PlaceboOdds ratio (95% CI)P value

Improvement

2.20(1.62–2.99)

P < 0.001

Deterioration

0.36(0.19–0.70)

P = 0.003

Further pooled results

Outcome	← Lower with semaglutide ←→ Higher with semaglutide →	Difference (points) (95% CI)
KCCQ-CSS, by baseline NYHA class (subgroup)Semaglutide vs Placebo · NYHA III/IV	−1001020	10.5 (6.6–14.4)
KCCQ-CSS, by baseline NYHA class (subgroup)Semaglutide vs Placebo · NYHA II	−1001020	6.0 (3.4–8.6)
	−1001020Difference, points (linear scale)

Outcome	← Lower with semaglutide ←→ Higher with semaglutide →	Difference (95% CI)
Bodyweight, by baseline NYHA class (subgroup)Semaglutide vs Placebo · NYHA II	−10−505	−8.4% (−9.4% to −7.3%)
Bodyweight, by baseline NYHA class (subgroup)Semaglutide vs Placebo · NYHA III/IV	−10−505	−8.3% (−9.9% to −6.8%)
	−10−505Difference (linear scale)

KCCQ-CSS, by baseline NYHA class (subgroup): P interaction = 0.06
Bodyweight, by baseline NYHA class (subgroup): P interaction = 0.96

6MWD, hierarchical composite endpoint, CRP, NT-proBNP, by baseline NYHA class

Semaglutide consistently improved 6MWD and the hierarchical composite endpoint and reduced CRP and NT-proBNP across NYHA class categories: all P interactions = NS

Original publication

Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program. J Am Coll Cardiol. Published 23 June 2024. doi:10.1016/j.jacc.2024.04.038

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Summarised from the published abstract; every number is checked against it