Incretin receptor agonists in heart failure with preserved ejection fraction and obesity
In adults with heart failure with preserved ejection fraction and obesity, what is the effect of an incretin receptor agonist on symptoms and on heart-failure events?
§1Abstract
§1.1Review question
In adults with heart failure with preserved ejection fraction and obesity, what is the effect of an incretin receptor agonist on symptoms and on heart-failure events?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Adults with heart failure with preserved ejection fraction and a body-mass index of 30 kg/m² or above. |
| Intervention | Semaglutide 2.4 mg or tirzepatide at an evaluated dose. |
| Comparator | Placebo. |
| Outcomes | Change in the Kansas City Cardiomyopathy Questionnaire clinical summary score; six-minute walk distance; composite of cardiovascular death and worsening heart failure. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 21 October 2023 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1]
§1.4Conclusion
Moderate certainty evidence indicates an improvement in symptom scores and in six-minute walk distance, and one trial reports a reduction in a composite of cardiovascular death and worsening heart failure. The Institute downgrades the symptom outcome one level for risk of bias, because weight change is visible to participants and the primary endpoint is patient-reported. The event outcome is downgraded for imprecision rather than for bias.
The conclusion rests on 3 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: Incretin receptor agonists in heart failure with preserved ejection fraction and obesity received 4 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, Hovingh GK, Kitzman DW, Lindegaard ML, Møller DV, Shah SJ, Treppendahl MB, Verma S, Abhayaratna W, Ahmed FZ, Chopra V, Ezekowitz J, Fu M, Ito H, Petrie MC. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. New England Journal of Medicine 2023;389(12):1069–1084. doi:10.1056/NEJMoa2306963 · PMID 37622681
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.