Wegovy improves functional class in patients with obesity, heart failure at 1 year
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Key takeaways:
- Wegovy improved functional class vs. placebo at 1 year in patients with obesity-driven heart failure with preserved ejection fraction.
- Weight loss with Wegovy was consistent across functional classes.
In patients with obesity-driven heart failure with preserved ejection fraction, semaglutide 2.4 mg was associated with more improvement in NYHA functional class compared with placebo, according to new data from the STEP-HFpEF trials.
The researchers conducted a prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials to determine the effect of once-weekly semaglutide 2.4 mg (Wegovy, Novo Nordisk) on NYHA functional class at 1 year. The analysis, published in the Journal of the American College of Cardiology, included 1,145 patients with obesity-driven HFpEF; those without diabetes were enrolled in STEP-HFpEF and those with diabetes were enrolled in STEP-HFpEF DM. Among the cohort, 69% had NYHA class II HF at baseline (35% < age 65 years; 46% women) and the rest had NYHA class III or IV HF at baseline (27% < age 65 years; 58% women).
As Healio previously reported, in the STEP-HFpEF program, compared with placebo, semaglutide 2.4 mg has been associated with reduced HF symptom burden and improvement in 6-minute walk distance and body weight in patients without diabetes and patients with diabetes; with reduced need for diuretics; and with improved HF symptoms for men and women but more weight loss in women. The results have been consistent regardless of baseline EF and baseline diuretic use.
Improved NYHA class
At 1 year, compared with the placebo group, the semaglutide 2.4 mg group was more likely to improve in NYHA class (32.6% vs. 21.5%; OR = 2.2; 95% CI, 1.62-2.99; P < .001) and was less likely to deteriorate in NYHA class (2.09% vs. 5.24%; OR = 0.36; 95% CI, 0.19-0.7; P = .003), Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City School of Medicine, and colleagues wrote.
Across all baseline functional classes, the semaglutide 2.4 mg group had greater improvement in the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CCS) at 1 year, and the treatment effect was greatest in those with worse functional class at baseline (NYHA class III/IV: difference in improvement, 10.5 points; NYHA class II: difference in improvement, 6 points; P for interaction = .06), the researchers found.
Weight loss was greater in the semaglutide 2.4 mg group in all functional classes and the difference vs. placebo was consistent regardless of functional class (NYHA functional class II, –8.4%; NYHA functional classes III/IV, –8.3%; P for interaction = .96), Kosiborod and colleagues found.
Compared with placebo, semaglutide 2.4 mg consistently improved the following outcomes across functional classes: 6-minute walk distance; a hierarchical composite endpoint of death, HF events, differences in KCCQ-CSS and change in 6-minute walk distance; C-reactive protein level and N-terminal pro-B-type natriuretic peptide level.
‘Reassuring and clinically relevant’
“The finding that semaglutide has a consistent effect across the endpoints in the STEP-HFpEF program is reassuring and clinically relevant,” Kosiborod and colleagues wrote. “The finding that semaglutide, while leading to a quantitatively large improvement in HF-related symptoms and physical limitations in patients with NYHA functional class II, appears to have an even greater benefit in terms of improvement in KCCQ-CSS among those with more severe functional limitations (NYHA functional classes III/IV) is especially noteworthy.”
Perspective
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Gregg C. Fonarow, MD, FACC, FAHA, FHFSA
There is impressive efficacy with semaglutide in patients with HFpEF and obesity that are seen across the spectrum of functional impairment as indexed by NYHA functional class in improving patient-centered outcomes.
Importantly, safety and tolerability were good, even in those with greater functional impairment at baseline.
The mechanisms responsible for the clinical benefit found are likely multidimensional. Clinically relevant and rapid weight loss is likely contributing. However, there was rapid improvement in the biomarker NT-proBNP. Further, a significant reduction in C-reactive protein was found across baseline NYHA functional class, suggesting there is a potent anti-inflammatory mechanism that may be contributing. Favorable systemic and potentially coronary vascular effects of semaglutide may also be contributing.
These findings suggest that semaglutide should be prescribed irrespective of NYHA functional class for otherwise eligible patients with obesity-related HFpEF.
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