Summary:
In 1,145 patients with obesity-related HFpEF (BMI ≥30, LVEF ≥45%) from pooled STEP-HFpEF trials, stratified by baseline NT-proBNP tertiles, semaglutide 2.4 mg subcutaneous weekly for 52 weeks significantly reduced NT-proBNP, with KCCQ improvements greatest in highest NT-proBNP tertile (up to 11.9 points) compared to matching placebo, with consistent weight loss (~8%) across all NT-proBNP tertiles regardless of cardiac disease severity.
| PICO | Description |
|---|---|
| Population | 1,145 patients with obesity-related HFpEF (BMI ≥30, LVEF ≥45%), stratified by NT-proBNP tertiles. |
| Intervention | Semaglutide 2.4 mg subcutaneous weekly for 52 weeks. |
| Comparison | Matching placebo weekly, double-blind. |
| Outcome | NT-proBNP reduced. KCCQ up to +11.9 in highest tertile. Weight -8% consistent across tertiles. |
Semaglutide and NT-proBNP in obesity-related HFpEF
Pooled STEP-HFpEF · prespecified analysis · 52 weeks
Semaglutide reduced NT-proBNP, and KCCQ symptom/physical-limitation gains were largest in the highest baseline NT-proBNP tertile despite similar weight loss across tertiles.
Clinical Context
NT-proBNP correlates with HFpEF severity and outcomes. Higher levels indicate greater cardiac stress.
Clinical Pearls
1. Sicker Patients Benefit More: Highest NT-proBNP tertile showed largest QoL improvements.
2. NT-proBNP as Treatment Guide: Baseline levels help identify patients likely to experience greatest benefit.
3. Cardiac Unloading Beyond Weight Loss: NT-proBNP reduction suggests cardiac benefit beyond weight loss alone.
4. Consistent Weight Loss: ~8% reduction similar across NT-proBNP tertiles.
Practical Application
Consider semaglutide especially for HFpEF patients with elevated NT-proBNP. Monitor NT-proBNP along with symptoms during treatment.
Study Limitations
NT-proBNP is a surrogate marker. 52-week follow-up. Specific thresholds not defined.
Bottom Line
Semaglutide reduces NT-proBNP with greatest QoL benefits in highest baseline NT-proBNP tertile. Sicker patients benefit most.
Source: Petrie MC, et al. “Semaglutide and NT-proBNP in Obesity-Related HFpEF.” J Am Coll Cardiol. 2024. Read article