Pooled analysis links semaglutide to fewer heart failure events in HFpEF
A pooled analysis of four trials suggests semaglutide may reduce heart failure hospitalizations in people with HFpEF, a common form of heart failure with few treatment options.
A pooled analysis of four randomized trials found that once-weekly injectable semaglutide reduced the combined risk of cardiovascular death or a worsening heart failure event by 31% in people with heart failure with preserved ejection fraction, a condition called HFpEF [1]. The analysis covered 3,743 participants with a history of HFpEF and was funded by Novo Nordisk, which sells semaglutide [1].
The findings come from a post-hoc, participant-level pooling of four placebo-controlled trials: SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM [1]. Together the trials assigned 22,282 people. Of those, 3,743 — 16.8% — had a history of HFpEF: 1,914 assigned to semaglutide and 1,829 to placebo [1]. Three of the trials (SELECT, STEP-HFpEF, and STEP-HFpEF DM) tested a once-weekly 2.4 mg subcutaneous dose; FLOW tested 1.0 mg once weekly [1]. All four trials are complete [1].
In the HFpEF group, 103 people taking semaglutide (5.4%) had a cardiovascular death or a first worsening heart failure event — a hospitalization or an urgent visit for heart failure — compared with 138 people taking placebo (7.5%). That works out to a hazard ratio of 0.69 (95% CI 0.53-0.89; p=0.0045) [1]. Worsening heart failure events on their own fell from 86 (4.7%) in the placebo group to 54 (2.8%) with semaglutide (HR 0.59; 95% CI 0.41-0.82; p=0.0019) [1].
Cardiovascular death by itself did not differ significantly: 59 deaths (3.1%) with semaglutide versus 67 (3.7%) with placebo (HR 0.82; 95% CI 0.57-1.16; p=0.25) [1]. A smaller share of participants taking semaglutide had serious adverse events, 572 (29.9%) versus 708 (38.7%) on placebo [1].
The analysis has limits. It is a post-hoc look at data gathered for other purposes, not a trial designed in advance to test heart failure events in HFpEF [1]. The four trials enrolled different groups: STEP-HFpEF and STEP-HFpEF DM enrolled people with obesity-related HFpEF, SELECT enrolled people with atherosclerotic cardiovascular disease and overweight or obesity, and FLOW enrolled people with type 2 diabetes and chronic kidney disease [1]. For SELECT and FLOW participants, HFpEF was identified from an investigator-reported history rather than a required enrollment diagnosis [1].
Why it matters for patients
HFpEF is the most common type of heart failure and carries a high risk of hospitalization and death, especially in people who have overweight, obesity, or type 2 diabetes [1]. In the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide had already been shown to improve heart failure-related symptoms and physical limitations in this group; whether it also cut hard events such as hospitalizations was an open question before this analysis [1].
The authors conclude that the data support using semaglutide to reduce the risk of clinical heart failure events in patients with HFpEF, "for whom few treatment options are currently available" [1]. That is a statement about a group average across a pooled dataset, not a prediction for any one person, and the analysis does not address dosing or which patients are most likely to benefit. Whether the results change how semaglutide is prescribed or labeled for heart failure has not been disclosed. Because the pooled population excluded people without the conditions studied in each trial, it is not known how the findings apply to other groups of patients with HFpEF [1].
What happens next
All four trials included in the analysis are complete, and no new trial of semaglutide in HFpEF is described in the analysis [1]. No regulatory filing or label change based on these results has been reported. The trials are registered as NCT03574597 (SELECT), NCT03819153 (FLOW), NCT04788511 (STEP-HFpEF), and NCT04916470 (STEP-HFpEF DM) [1]. Semaglutide is also sold as Ozempic, Wegovy, and Rybelsus.
Sources
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