Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction: SATELLITE Trial Results
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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.
In: Journal of Cardiac Failure, Vol. 30, No. 1, 2024, p. 104-110.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Myeloperoxidase Inhibition in Heart Failure With Preserved or Mildly Reduced Ejection Fraction
T2 - SATELLITE Trial Results
AU - Lam, Carolyn S.P.
AU - Lund, Lars H.
AU - Shah, Sanjiv J.
AU - Voors, Adriaan A.
AU - Erlinge, David
AU - Saraste, Antti
AU - Pirazzi, Carlo
AU - Grove, Erik L.
AU - Barasa, Anders
AU - Schou, Morten
AU - Aziz, Ahmed
AU - Svedlund, Sara
AU - Wijngaarden, Jan Van
AU - Lindstedt, Eva-Lotte
AU - Gustavsson, Andreas
AU - Nelander, Karin
AU - Garkaviy, Pavlo
AU - Gan, Li-Ming
AU - Gabrielsen, Anders
N1 - Publisher Copyright: © 2023 The Authors
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - Heart failure
KW - inflammation
KW - mildly reduced ejection fraction
KW - myeloperoxidase
KW - pharmacodynamics
KW - pharmacokinetics
KW - preserved ejection fraction
KW - randomized controlled trial
U2 - 10.1016/j.cardfail.2023.04.003
DO - 10.1016/j.cardfail.2023.04.003
M3 - Journal article
C2 - 37072105
AN - SCOPUS:85162224469
VL - 30
SP - 104
EP - 110
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
SN - 1071-9164
IS - 1
ER -
ID: 369123784