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Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study.

Publication ,  Journal Article
Felker, GM; McMurray, JJV; Cleland, JG; O'Connor, CM; Teerlink, JR; Voors, AA; Belohlavek, J; Böhm, M; Borentain, M; Bueno, H; Cole, RT; Ye, J ...
Published in: JACC Heart Fail
February 2021

OBJECTIVES: The primary objective was to identify well-tolerated doses of cimlanod in patients with acute heart failure (AHF). Secondary objectives were to identify signals of efficacy, including biomarkers, symptoms, and clinical events. BACKGROUND: Nitroxyl (HNO) donors have vasodilator, inotropic and lusitropic effects. Bristol-Myers Squibb-986231 (cimlanod) is an HNO donor being developed for acute heart failure (AHF). METHODS: This was a phase IIb, double-blind, randomized, placebo-controlled trial of 48-h treatment with cimlanod compared with placebo in patients with left ventricular ejection fraction ≤40% hospitalized for AHF. In part I, patients were randomized in a 1:1 ratio to escalating doses of cimlanod or matching placebo. In part II, patients were randomized in a 1:1:1 ratio to either of the 2 highest tolerated doses of cimlanod from part I or placebo. The primary endpoint was the rate of clinically relevant hypotension (systolic blood pressure <90 mm Hg or patients became symptomatic). RESULTS: In part I (n = 100), clinically relevant hypotension was more common with cimlanod than placebo (20% vs. 8%; relative risk [RR]: 2.45; 95% confidence interval [CI]: 0.83 to 14.53). In part II (n = 222), the incidence of clinically relevant hypotension was 18% for placebo, 21% for cimlanod 6 μg/kg/min (RR: 1.15; 95% CI: 0.58 to 2.43), and 35% for cimlanod 12 μg/kg/min (RR: 1.9; 95% CI: 1.04 to 3.59). N-terminal pro-B-type natriuretic peptide and bilirubin decreased during infusion of cimlanod treatment compared with placebo, but these differences did not persist after treatment discontinuation. CONCLUSIONS: Cimlanod at a dose of 6 μg/kg/min was reasonably well-tolerated compared with placebo. Cimlanod reduced markers of congestion, but this did not persist beyond the treatment period. (Evaluate the Safety and Efficacy of 48-Hour Infusions of HNO (Nitroxyl) Donor in Hospitalized Patients With Heart Failure [STANDUP AHF]; NCT03016325).

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Published In

JACC Heart Fail

DOI

EISSN

2213-1787

Publication Date

February 2021

Volume

9

Issue

2

Start / End Page

146 / 157

Location

United States

Related Subject Headings

  • Ventricular Function, Left
  • Treatment Outcome
  • Stroke Volume
  • Nitrogen Oxides
  • Humans
  • Heart Failure
  • Double-Blind Method
  • Acute Disease
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology
 

Citation

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Felker, G. M., McMurray, J. J. V., Cleland, J. G., O’Connor, C. M., Teerlink, J. R., Voors, A. A., … Ye, J. (2021). Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study. JACC Heart Fail, 9(2), 146–157. https://doi.org/10.1016/j.jchf.2020.10.012
Felker, G Michael, John J. V. McMurray, John G. Cleland, Christopher M. O’Connor, John R. Teerlink, Adriaan A. Voors, Jan Belohlavek, et al. “Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study.JACC Heart Fail 9, no. 2 (February 2021): 146–57. https://doi.org/10.1016/j.jchf.2020.10.012.
Felker GM, McMurray JJV, Cleland JG, O’Connor CM, Teerlink JR, Voors AA, et al. Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study. JACC Heart Fail. 2021 Feb;9(2):146–57.
Felker, G. Michael, et al. “Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study.JACC Heart Fail, vol. 9, no. 2, Feb. 2021, pp. 146–57. Pubmed, doi:10.1016/j.jchf.2020.10.012.
Felker GM, McMurray JJV, Cleland JG, O’Connor CM, Teerlink JR, Voors AA, Belohlavek J, Böhm M, Borentain M, Bueno H, Cole RT, DeSouza MM, Ezekowitz JA, Filippatos G, Lang NN, Kessler PD, Martinez FA, Mebazaa A, Metra M, Mosterd A, Pang PS, Ponikowski P, Sato N, Seiffert D, Ye J. Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study. JACC Heart Fail. 2021 Feb;9(2):146–157.
Journal cover image

Published In

JACC Heart Fail

DOI

EISSN

2213-1787

Publication Date

February 2021

Volume

9

Issue

2

Start / End Page

146 / 157

Location

United States

Related Subject Headings

  • Ventricular Function, Left
  • Treatment Outcome
  • Stroke Volume
  • Nitrogen Oxides
  • Humans
  • Heart Failure
  • Double-Blind Method
  • Acute Disease
  • 3201 Cardiovascular medicine and haematology
  • 1102 Cardiorespiratory Medicine and Haematology