PMID- 36082522 OWN - NLM STAT- MEDLINE DCOM- 20221215 LR - 20230413 IS - 1463-1326 (Electronic) IS - 1462-8902 (Print) IS - 1462-8902 (Linking) VI - 25 IP - 1 DP - 2023 Jan TI - Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial. PG - 189-197 LID - 10.1111/dom.14862 [doi] AB - AIM: To perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF). MATERIALS AND METHODS: FIGHT was a double-blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all-cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression. RESULTS: Compared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all-cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98-2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92-3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06-1.92; P = 0.018). The risk of HF hospitalizations or all-cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21-2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31-1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047). CONCLUSIONS: In patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis-generating. Further RCTs must be conducted before drawing definitive conclusions. CI - (c) 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. FAU - Neves, Joao Sergio AU - Neves JS AUID- ORCID: 0000-0002-8173-8255 AD - Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal. FAU - Vasques-Novoa, Francisco AU - Vasques-Novoa F AD - Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Internal Medicine, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal. FAU - Borges-Canha, Marta AU - Borges-Canha M AUID- ORCID: 0000-0003-2929-3751 AD - Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal. FAU - Leite, Ana Rita AU - Leite AR AD - Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. FAU - Sharma, Abhinav AU - Sharma A AD - Division of Cardiology, DREAM-CV Lab, McGill University Health Centre, Montreal, Canada. FAU - Carvalho, Davide AU - Carvalho D AUID- ORCID: 0000-0002-3156-3741 AD - Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal. AD - Instituto de Investigacao e Inovacao em Saude, Universidade do Porto, Porto, Portugal. FAU - Packer, Milton AU - Packer M AUID- ORCID: 0000-0003-1828-2387 AD - Baylor Heart and Vascular Institute, Baylor University Medical Center, Dallas, Texas, USA. AD - Imperial College, London, UK. FAU - Zannad, Faiez AU - Zannad F AD - Universite de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithematique 14-33, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. FAU - Leite-Moreira, Adelino AU - Leite-Moreira A AD - Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Department of Cardiothoracic Surgery, Centro Hospitalar Universitario Sao Joao, Porto, Portugal. FAU - Ferreira, Joao Pedro AU - Ferreira JP AUID- ORCID: 0000-0002-2304-6138 AD - Cardiovascular R&D Centre-UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal. AD - Universite de Lorraine, Inserm, Centre d'Investigations Cliniques, Plurithematique 14-33, and Inserm U1116, CHRU Nancy, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. LA - eng GR - U10 HL084904/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial DEP - 20220921 PL - England TA - Diabetes Obes Metab JT - Diabetes, obesity & metabolism JID - 100883645 RN - 839I73S42A (Liraglutide) SB - IM MH - Humans MH - *Liraglutide/adverse effects MH - *Heart Failure/drug therapy PMC - PMC9742170 MID - NIHMS1834611 OTO - NOTNLM OT - GLP-1 receptor agonists OT - adverse events OT - arrhythmia OT - heart failure hospitalizations OT - heart failure with reduced ejection fraction OT - liraglutide COIS- Dr Neves has received consulting or speaker fees from AstraZeneca, BIAL, Boehringer Ingelheim, Lilly, Merck and Novo Nordisk. Dr Sharma is supported by the McGill University Health Centre (MUHC) Foundation, Montreal General Hospital (MGH) Foundation, Sarah Louise King Award, Marjorie Cadham Award, Inez and Willena Beaton Award, Fonds de Recherche Sante Quebec (FRSQ) Junior 1 clinician scholars' program, and Canada Institute for Health Research grant - 175 095. Dr Sharma reports receiving support from the European Society of Cardiology young investigator grant, Roche Diagnostics, Boehringer-Ingelheim, Novartis and Takeda. Dr Carvalho has received consultancy fees from Novo-Nordisk and Eli-Lilly, and has held lectures Novo-Nordisk, Eli-Lilly and Astra-Zeneca. Dr Packer has received personal fees from Abbvie, Actavis, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Caladrius, Casana, CSL Behring, Cytokinetics, Imara, Lilly, Moderna, Novartis, Reata, Relypsa and Salamandras. Dr Zannad reports personal fees from Boehringer Ingelheim, Janssen, Novartis, Boston Scientific, Amgen, CVRx, AstraZeneca, Vifor Fresenius, Cardior, Cereno Pharmaceutical, Applied Therapeutics, Merck, Bayer and Cellprothera, outside the submitted work, and other support from CVCT and Cardiorenal, outside the submitted work. Dr Ferreira is a consultant for Boehringer-Ingelheim, and receives research support from AstraZeneca and Novartis. All other authors have no potential conflicts of interest to disclose. EDAT- 2022/09/10 06:00 MHDA- 2022/12/15 06:00 PMCR- 2023/04/11 CRDT- 2022/09/09 03:53 PHST- 2022/08/25 00:00 [revised] PHST- 2022/07/22 00:00 [received] PHST- 2022/09/04 00:00 [accepted] PHST- 2022/09/10 06:00 [pubmed] PHST- 2022/12/15 06:00 [medline] PHST- 2022/09/09 03:53 [entrez] PHST- 2023/04/11 00:00 [pmc-release] AID - DOM14862 [pii] AID - 10.1111/dom.14862 [doi] PST - ppublish SO - Diabetes Obes Metab. 2023 Jan;25(1):189-197. doi: 10.1111/dom.14862. Epub 2022 Sep 21.