Summary: In this prespecified analysis of the SELECT trial, once-weekly semaglutide 2.4 mg reduced major adverse cardiovascular events (HR 0.72, 95% CI 0.60 to 0.87) and a composite heart failure endpoint (HR 0.79, 95% CI 0.64 to 0.98) in the 4286 of 17604 enrolled patients (24.3%) who had heart failure at baseline. The benefit was directionally consistent across heart failure subtypes, although this was a subgroup analysis of patients with established atherosclerotic disease and overweight or obesity.
PICO Summary
| Element | Detail |
|---|---|
| Population | Prespecified subgroup of the SELECT phase 3 RCT: 4286 of 17604 adults (24.3%) aged 45 years or older with BMI 27 kg/m2 or greater, established atherosclerotic cardiovascular disease, and investigator-defined heart failure at enrolment (53.0% HFpEF, 31.4% HFrEF, 15.5% unclassified); multicentre, 41 countries. |
| Intervention | Once-weekly subcutaneous semaglutide, escalated over 16 weeks to a target dose of 2.4 mg (overall trial n=8803). |
| Comparison | Matching once-weekly subcutaneous placebo with standard care, double-blind (overall trial n=8801). |
| Outcome | In patients with heart failure at baseline: MACE HR 0.72 (95% CI 0.60 to 0.87); composite heart failure endpoint (CV death or hospitalisation or urgent visit for heart failure) HR 0.79 (95% CI 0.64 to 0.98); cardiovascular death HR 0.76 (95% CI 0.59 to 0.97); all-cause death HR 0.81 (95% CI 0.66 to 1.00, upper bound at unity). All interaction p values for benefit by heart failure status were greater than 0.19, indicating consistency of effect across patients with and without heart failure. Serious adverse events were less frequent with semaglutide. ARR and NNT were not reported in the abstract. |
SELECT: semaglutide with prevalent heart failure
Prespecified RCT analysis · obesity + ASCVD
In SELECT participants with heart failure at baseline, semaglutide 2.4 mg cut MACE and a composite heart failure endpoint versus placebo, consistently across HFpEF and HFrEF. It remains a subgroup of an atherosclerotic-disease population, not a dedicated heart failure trial.
Expert Commentary
This prespecified analysis supports the view that the cardiovascular benefit of semaglutide 2.4 mg observed in the parent SELECT trial is preserved, and not attenuated, in the substantial proportion of participants who carried a diagnosis of heart failure at entry. The reductions in major adverse cardiovascular events and the composite heart failure endpoint are consistent across heart failure with preserved and reduced ejection fraction, which is reassuring given how often obesity coexists with HFpEF. The verdict is that the signal is credible and clinically relevant, yet it should be read for what it is: a subgroup analysis of patients already selected for established atherosclerotic disease, not a dedicated heart failure outcomes trial. The most weighable limitation is that heart failure status was investigator-defined rather than adjudicated against objective criteria, so subtype misclassification is plausible and the all-cause mortality estimate reaches unity at its upper bound. Industry sponsorship by the manufacturer, Novo Nordisk, with several company authors, also warrants the usual caution. Can I use this with my patients? Yes, for an adult with overweight or obesity and established atherosclerotic cardiovascular disease who also has heart failure, this strengthens the case for semaglutide, while dedicated trials such as STEP-HFpEF remain the primary evidence for heart failure symptoms. Confirmatory adjudicated heart failure endpoints would be welcome.
References
Deanfield J, Verma S, Scirica BM, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. Lancet. 2024;404(10454):773-786. doi:10.1016/S0140-6736(24)01498-3