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GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis

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Abstract

Aims

Glucagon-like peptide-1 receptor agonists (GLP1-ra) have shown to reduce cardiovascular (CV) events in patients with diabetes, including heart failure (HF) hospitalizations. However, whether such benefit consistently occurs in patients with history of HF remains uncertain. We performed a systematic review and meta-analysis to assess the impact of GLP1-ra on CV outcomes in patients with and without HF history.

Methods and results

All randomized, placebo-controlled trials evaluating GLP1-ra and reporting CV outcomes stratified by HF history were searched in Pubmed from inception to November 12th, 2023. The primary outcome was HF hospitalizations. Secondary outcomes included CV death, the composite of CV death and hospitalizations for HF, and major adverse cardiovascular events (MACE). Hazard ratio (HR) and 95% confidence interval (CIs) were used as effect estimates and calculated with a random-effects model. 68,653 patients (GLP1-ra = 34,301, placebo = 34,352) from 10 trials were included. GLP1-ra reduced HF hospitalization (no HF: HR = 0.79, 95% CI 0.63–0.98; HF: HR = 1.00, 95% CI 0.82–1.24, pinteraction = 0.12), CV death (no HF: HR = 0.81, 95% CI 0.71–0.92; HF: HR = 0.97, 95% CI 0.81–1.15, pinteraction = 0.11), and the composite of HF hospitalizations and CV death (no HF: HR = 0.80, 95% CI 0.72–0.89; HF: HR = 1.00 95% CI 0.88–1.15, pinteraction = 0.010) only in patients without history of HF, despite a significant interaction between HF history and treatment effect was detected only for the latter. MACE were reduced in both subgroups without significant interaction between HF history and treatment effect (no HF: HR = 0.86, 95% CI 0.78–0.96; HF: HR = 0.83, 95% CI 0.72–0.95, pinteraction = 0.69).

Conclusion

GLP1-ra do not decrease HF-hospitalization risk, despite a potential benefit in patients without history of HF, but are effective in reducing ischemic events irrespective of the presence of HF.

PROSPERO-registered (CRD42022371264).

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Data availability statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

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Correspondence to Giulio G. Stefanini or Mauro Chiarito.

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Dr. Mehran reports grants from Abbott Laboratories, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, OrbusNeich; personal fees from Abbott Laboratories, Boston Scientific, Medscape/WebMD, Siemens Medical Solutions, PLx Opco Inc/dba PLx Pharma Inc, Roivant Sciences, Sanofi, Medtelligence (Janssen Scientific Affairs), Janssen Scientific Affairs; other from Abbott laboratories, other from Abiomed, other from Bristol Myers Squibb, other from Claret Medical, other from Elixir Medical, other from The Medicines eCompany, other from Spectranetics/Philips/Volcano Corp, other from Watermark Research Partners; non-financial support and other from Regeneron Pharmaceuticals, Idorsia Pharmaceuticals Ltd. Dr. Reimers has received speaker honoraria from Boston Scientific. Dr. Pagnesi reports personal fees from Abbott Laboratories, AstraZeneca, Boehringer Ingelheim and Vifor Pharma, all outside the submitted work. Dr. Metra reports personal consulting honoraria of minimal amount from Abbott, Amgen, Bayer, Edwards Therapeutics, LivaNova and Vifor Pharma for participation to advisory board meetings and executive committees of clinical trials. Dr. Savarese reports grants and personal fees from Vifor, grants and personal fees from AstraZeneca, personal fees from Servier, grants and personal fees from Novartis, grants and personal fees from Cytokinetics, grants and personal fees from Pharmacosmos, personal fees from Medtronic, grants from Boston Scientific, grants from Merck, grants from Bayer outside the submitted work. Dr. Stefanini reports a research grant from Boston Scientific and speaker or consulting fees from B. Braun, Biosensors, and Boston Scientific. All other authors report no relationships relevant to the contents of this paper to disclose.

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Villaschi, A., Ferrante, G., Cannata, F. et al. GLP-1-ra and heart failure-related outcomes in patients with and without history of heart failure: an updated systematic review and meta-analysis. Clin Res Cardiol 113, 898–909 (2024). https://doi.org/10.1007/s00392-023-02362-6

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