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Repurposing the β3-adrenergic receptor agonist Mirabegron in patients with structural cardiac disease

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dc.contributor.authorBalligand, Jean-Luc
dc.contributor.authorBrito, Dulce
dc.contributor.authorBrosteanu, Oana
dc.contributor.authorCasadei, Barbara
dc.contributor.authorDepoix, Christophe
dc.contributor.authorEdelmann, Frank
dc.contributor.authorFerreira, Vanessa
dc.contributor.authorFilippatos, Gerasimos
dc.contributor.authorGerber, Bernhard
dc.contributor.authorGruson, Damien
dc.contributor.authorHasenclever, Dirk
dc.contributor.authorHellenkamp, Kristian
dc.contributor.authorIkonomidis, Ignatios
dc.contributor.authorKrakowiak, Bartosz
dc.contributor.authorLhommel, Renaud
dc.contributor.authorMahmod, Masliza
dc.contributor.authorNeubauer, Stefan
dc.contributor.authorPersu, Alexandre
dc.contributor.authorPiechnik, Stefan
dc.contributor.authorPieske, Burkert
dc.contributor.authorPieske-Kraigher, Elisabeth
dc.contributor.authorPinto, Fausto J.
dc.contributor.authorPonikowski, Piotr
dc.contributor.authorSenni, Michele
dc.contributor.authorTrochu, Jean-Noël
dc.contributor.authorVan Overstraeten, Nancy
dc.contributor.authorWachter, Rolf
dc.contributor.authorPouleur, Anne-Catherine
dc.date.accessioned2024-07-24T10:26:23Z
dc.date.available2024-07-24T10:26:23Z
dc.date.issued2023
dc.description© 2023 Balligand JL et al. JAMA Cardiology. This is an open access article distributed under the terms of the CC-BY License.pt_PT
dc.description.abstractImportance: Left ventricular (LV) hypertrophy contributes to the onset and progression of heart failure (HF), particularly for patients with pre-HF (stage B) for whom no treatment has yet proven effective to prevent transition to overt HF (stage C). The β3-adrenergic receptors (β3ARs) may represent a new target, as their activation attenuates LV remodeling. Objective: To determine whether activation of β3ARs by repurposing a β3AR agonist, mirabegron, is safe and effective in preventing progression of LV hypertrophy and diastolic dysfunction among patients with pre- or mild HF. Design, setting, and participants: The Beta3-LVH prospective, triple-blind, placebo-controlled phase 2b randomized clinical trial enrolled patients between September 12, 2016, and February 26, 2021, with a follow-up of 12 months. The trial was conducted at 10 academic hospitals in 8 countries across Europe (Germany, Poland, France, Belgium, Italy, Portugal, Greece, and the UK). Patients aged 18 years or older with or without HF symptoms (maximum New York Heart Association class II) were screened for the presence of LV hypertrophy (increased LV mass index [LVMI] of ≥95 g/m2 for women or ≥115 g/m2 for men) or maximum wall thickness of 13 mm or greater using echocardiography. Data analysis was performed in August 2022. Intervention: Participants were randomly assigned (1:1) to mirabegron (50 mg/d) or placebo, stratified by the presence of atrial fibrillation and/or type 2 diabetes, for 12 months. Main outcomes and measures: The primary end points were LVMI determined using cardiac magnetic resonance imaging and LV diastolic function (early diastolic tissue Doppler velocity [E/e'] ratio assessed using Doppler echocardiography) at 12 months. Patients with at least 1 valid measurement of either primary end point were included in the primary analysis. Safety was assessed for all patients who received at least 1 dose of study medication. Results: Of the 380 patients screened, 296 were enrolled in the trial. There were 147 patients randomized to mirabegron (116 men [79%]; mean [SD] age, 64.0 [10.2] years) and 149 to placebo (112 men [75%]; mean [SD] age, 62.2 [10.9] years). All patients were included in the primary intention-to-treat analysis. At 12 months, the baseline and covariate-adjusted differences between groups included a 1.3-g/m2 increase in LVMI (95% CI, -0.15 to 2.74; P = .08) and a -0.15 decrease in E/e' (95% CI, -0.69 to 0.4; P = .60). A total of 213 adverse events (AEs) occurred in 82 mirabegron-treated patients (including 31 serious AEs in 19 patients) and 215 AEs occurred in 88 placebo-treated patients (including 30 serious AEs in 22 patients). No deaths occurred during the trial. Conclusions: In this study, mirabegron therapy had a neutral effect on LV mass or diastolic function over 12 months among patients who had structural heart disease with no or mild HF symptoms.pt_PT
dc.description.sponsorshipThis study was funded by European Commission Horizon 2020 Framework Programme grant 634559-Beta3LVH.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJAMA Cardiol. 2023 Nov 1;8(11):1031-1040pt_PT
dc.identifier.doi10.1001/jamacardio.2023.3003pt_PT
dc.identifier.eissn2380-6591
dc.identifier.issn2380-6583
dc.identifier.urihttp://hdl.handle.net/10451/65431
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Medical Associationpt_PT
dc.relation634559-Beta3LVHpt_PT
dc.relation.publisherversionhttps://jamanetwork.com/journals/jamacardiologypt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titleRepurposing the β3-adrenergic receptor agonist Mirabegron in patients with structural cardiac diseasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage1040pt_PT
oaire.citation.issue11pt_PT
oaire.citation.startPage1031pt_PT
oaire.citation.titleJAMA Cardiologypt_PT
oaire.citation.volume8pt_PT
person.familyNameBrito
person.familyNamePinto
person.givenNameDulce
person.givenNameFausto J.
person.identifier1308889
person.identifier.ciencia-idF216-586F-1762
person.identifier.ciencia-idC311-AEDD-6DBB
person.identifier.orcid0000-0003-1278-1847
person.identifier.orcid0000-0002-8034-4529
person.identifier.ridG-9650-2016
person.identifier.ridG-9363-2015
person.identifier.scopus-author-id7004510538
person.identifier.scopus-author-id7102740158
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication196a2934-1434-433c-9735-81acb6fbe587
relation.isAuthorOfPublication5f44176f-69f5-482c-83cd-ab94425a6ec3
relation.isAuthorOfPublication.latestForDiscovery196a2934-1434-433c-9735-81acb6fbe587

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