ß3 adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial
Por:
García-Álvarez A., Blanco I., García-Lunar I., Jordà P., Rodriguez-Arias J.J., Fernández-Friera L., Zegri I., Nuche J., Gomez-Bueno M., Prat S., Pujadas S., Sole-Gonzalez E., Garcia-Cossio M.D., Rivas M., Torrecilla E., Pereda D., Sanchez J., García-Pavía P., Segovia-Cubero J., Delgado J.F., Mirabet S., Fuster V., Barberá J.A., Ibañez B.
Publicada:
1 ene 2022
Ahead of Print:
1 ene 2022
Resumen:
Aims: Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective ß3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH). Methods and results: The ß3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n = 39) or placebo (n = 41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] -0.38, 1.61, p = 0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p = 0.026), without significant differences in other pre-specified secondary outcomes. Conclusions: SPHERE-HF is the first clinical trial to assess the potential benefit of ß3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life. © 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
Filiaciones:
García-Álvarez A.:
Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Universitat de Barcelona, Barcelona, Spain
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Blanco I.:
Universitat de Barcelona, Barcelona, Spain
Department of Pulmonary Medicine, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
García-Lunar I.:
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Cardiology Department, University Hospital La Moraleja, Madrid, Spain
Jordà P.:
Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Rodriguez-Arias J.J.:
Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Fernández-Friera L.:
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
HM Hospitales-Centro Integral de Enfermedades Cardiovasculares HM-CIEC, Madrid, Spain
Zegri I.:
Cardiology Department, Hospital Santa Creu I Sant Pau, IIb-Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
Nuche J.:
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Department of Cardiology, University Hospital 12 de Octubre, Instituto de Investigación Sanitaria i+12, Universdad Complutense, Madrid, Spain
Gomez-Bueno M.:
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Department of Cardiology, University Hospital Puerta de Hierro-IDIPHISA, Universidad Autónoma de Madrid (UAM), Madrid, Spain
Prat S.:
Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Universitat de Barcelona, Barcelona, Spain
Pujadas S.:
Cardiology Department, Hospital Santa Creu I Sant Pau, IIb-Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
Sole-Gonzalez E.:
Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Garcia-Cossio M.D.:
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Department of Cardiology, University Hospital 12 de Octubre, Instituto de Investigación Sanitaria i+12, Universdad Complutense, Madrid, Spain
Rivas M.:
Cardiology Department, Hospital Santa Creu I Sant Pau, IIb-Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
Department of Cardiology, University Hospital Puerta de Hierro-IDIPHISA, Universidad Autónoma de Madrid (UAM), Madrid, Spain
Torrecilla E.:
Department of Cardiology, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Pereda D.:
Universitat de Barcelona, Barcelona, Spain
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Department of Cardiovascular Surgery, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Sanchez J.:
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Philips Healthcare Iberia, Madrid, Spain
García-Pavía P.:
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Department of Cardiology, University Hospital Puerta de Hierro-IDIPHISA, Universidad Autónoma de Madrid (UAM), Madrid, Spain
Segovia-Cubero J.:
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Department of Cardiology, University Hospital Puerta de Hierro-IDIPHISA, Universidad Autónoma de Madrid (UAM), Madrid, Spain
Delgado J.F.:
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Department of Cardiology, University Hospital 12 de Octubre, Instituto de Investigación Sanitaria i+12, Universdad Complutense, Madrid, Spain
Mirabet S.:
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Cardiology Department, Hospital Santa Creu I Sant Pau, IIb-Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain
Fuster V.:
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Barberá J.A.:
Universitat de Barcelona, Barcelona, Spain
Department of Pulmonary Medicine, Hospital Clínic Barcelona-IDIBAPS, Barcelona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
Ibañez B.:
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
IIS-Fundación Jiménez Diaz University Hospital, Madrid, Spain
hybrid, All Open Access; Hybrid Gold
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