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Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results.
Lam, Carolyn S P; Lund, Lars H; Shah, Sanjiv J; Voors, Adriaan A; Erlinge, David; Saraste, Antti; Pirazzi, Carlo; Grove, Erik L; Barasa, Anders; Schou, Morten; Aziz, Ahmed; Svedlund, Sara; Wijngaarden, Jan VAN; Lindstedt, Eva-Lotte; Gustavsson, Andreas; Nelander, Karin; Garkaviy, Pavlo; Gan, Li-Ming; Gabrielsen, Anders.
Afiliación
  • Lam CSP; National Heart Centre Singapore and Duke National University of Singapore, Singapore; University of Groningen and University Medical Centre Groningen, Groningen, the Netherlands. Electronic address: carolyn.lam@duke-nus.edu.sg.
  • Lund LH; Department of Medicine, Karolinska Institute, and Heart, Vascular and Neuro Theme, Karolinska University Hospital, Stockholm, Sweden.
  • Shah SJ; Northwestern University Feinberg School of Medicine, Chicago, Illinois.
  • Voors AA; University of Groningen and University Medical Centre Groningen, Groningen, the Netherlands.
  • Erlinge D; Skåne University Hospital, Lund, Sweden.
  • Saraste A; Heart Centre, Turku University Hospital and University of Turku, Turku, Finland.
  • Pirazzi C; Department of Cardiology, Sahlgrenska University Hospital and Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Grove EL; Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
  • Barasa A; Glostrup Hospital, Copenhagen, Denmark.
  • Schou M; Department of Cardiology, Herlev and Gentofte Hospital, Copenhagen, Denmark.
  • Aziz A; Odense University Hospital, Odense, Denmark.
  • Svedlund S; Department of Clinical Physiology, Sahlgrenska University Hospital and Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Wijngaarden JV; Department of Cardiology, Deventer Hospital, Deventer, the Netherlands.
  • Lindstedt EL; Research and Early Clinical Development, Cardiovascular, Renal and Metabolic, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Gustavsson A; Early Biometrics and Statistical Innovation, Data Science and AI, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Nelander K; Early Biometrics and Statistical Innovation, Data Science and AI, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Garkaviy P; Research and Early Clinical Development, Cardiovascular, Renal and Metabolic, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
  • Gan LM; Department of Cardiology, Sahlgrenska University Hospital and Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • Gabrielsen A; Research and Early Clinical Development, Cardiovascular, Renal and Metabolic, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
J Card Fail ; 30(1): 104-110, 2024 Jan.
Article en En | MEDLINE | ID: mdl-37072105
BACKGROUND: Inflammation is a key driver of heart failure with preserved left ventricular ejection fraction. AZD4831 inhibits extracellular myeloperoxidase, decreases inflammation, and improves microvascular function in preclinical disease models. METHODS AND RESULTS: In this double-blind phase 2a study (Safety and Tolerability Study of AZD4831 in Patients With Heart Failure [SATELLITE]; NCT03756285), patients with symptomatic heart failure, left ventricular ejection fraction of ≥40%, and elevated B-type natriuretic peptides were randomized 2:1 to once-daily oral AZD4831 5 mg or placebo for 90 days. We aimed to assess target engagement (primary end point: myeloperoxidase specific activity) and safety of AZD4831. Owing to coronavirus disease 2019, the study was terminated early after randomizing 41 patients (median age 74.0 years, 53.7% male). Myeloperoxidase activity was decreased by more than 50% from baseline to day 30 and day 90 in the AZD4831 group, with a placebo-adjusted decreased of 75% (95% confidence interval, 48, 88, nominal P < .001). No improvements were noted in secondary or exploratory end points, apart from a trend in Kansas City Cardiomyopathy Questionnaire overall summary score. No deaths or treatment-related serious adverse events occurred. AZD4831 treatment-related adverse events were generalized maculopapular rash, pruritus, and diarrhea (all n = 1). CONCLUSIONS: AZD4831 inhibited myeloperoxidase and was well tolerated in patients with heart failure and left ventricular ejection fraction of 40% or greater. Efficacy findings were exploratory owing to early termination, but warrant further clinical investigation of AZD4831. LAY SUMMARY: Few treatments are available for patients with the forms of heart failure known as heart failure with preserved or mildly reduced ejection fraction. Current treatments do not target inflammation, which may play an important role in this condition. We tested a new drug called AZD4831 (mitiperstat), which decreases inflammation by inhibiting the enzyme myeloperoxidase. Among the 41 patients in our clinical trial, AZD4831 had a good safety profile and inhibited myeloperoxidase by the expected amount. Results mean we can conduct further trials to see whether AZD4831 decreases the symptoms of heart failure and improves patients' ability to participate in physical exercise.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 3_ND / 4_TD / 6_ODS3_enfermedades_notrasmisibles Problema de salud: 3_diarrhea / 4_covid_19 / 4_diarrhoeal_infections / 6_cardiovascular_diseases / 6_other_circulatory_diseases Asunto principal: Insuficiencia Cardíaca Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Aged / Female / Humans / Male Idioma: En Revista: J Card Fail Asunto de la revista: CARDIOLOGIA Año: 2024 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Contexto en salud: 3_ND / 4_TD / 6_ODS3_enfermedades_notrasmisibles Problema de salud: 3_diarrhea / 4_covid_19 / 4_diarrhoeal_infections / 6_cardiovascular_diseases / 6_other_circulatory_diseases Asunto principal: Insuficiencia Cardíaca Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Aged / Female / Humans / Male Idioma: En Revista: J Card Fail Asunto de la revista: CARDIOLOGIA Año: 2024 Tipo del documento: Article
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