TY - JOUR
TI - Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study
AU - Felker, G.M.
AU - McMurray, J.J.V.
AU - Cleland, J.G.
AU - O'Connor, C.M.
AU - Teerlink, J.R.
AU - Voors, A.A.
AU - Belohlavek, J.
AU - Böhm, M.
AU - Borentain, M.
AU - Bueno, H.
AU - Cole, R.T.
AU - DeSouza, M.M.
AU - Ezekowitz, J.A.
AU - Filippatos, G.
AU - Lang, N.N.
AU - Kessler, P.D.
AU - Martinez, F.A.
AU - Mebazaa, A.
AU - Metra, M.
AU - Mosterd, A.
AU - Pang, P.S.
AU - Ponikowski, P.
AU - Sato, N.
AU - Seiffert, D.
AU - Ye, J.
JO - JACC: Heart Failure
PY - 2021
VL - 9
TODO - 2
SP - 146-157
PB - HANLEY & BELFUS-ELSEVIER INC
SN - 2213-1779
TODO - 10.1016/j.jchf.2020.10.012
TODO - amino terminal pro brain natriuretic peptide;  angiotensin receptor antagonist;  beta adrenergic receptor blocking agent;  bilirubin;  cimlanod;  dipeptidyl carboxypeptidase inhibitor;  enkephalinase inhibitor;  loop diuretic agent;  mineralocorticoid antagonist;  placebo;  sacubitril plus valsartan, acute heart failure;  aged;  Article;  bilirubin blood level;  cohort analysis;  continuous infusion;  controlled study;  dose response;  double blind procedure;  drug dose comparison;  drug dose escalation;  drug dose reduction;  drug effect;  drug efficacy;  drug fatality;  drug safety;  drug tolerability;  drug withdrawal;  dyspnea;  female;  heart failure with reduced ejection fraction;  heart left ventricle ejection fraction;  heart rate;  human;  hypotension;  major clinical study;  male;  multicenter study;  phase 2 clinical trial;  priority journal;  protein blood level;  randomized controlled trial
TODO - 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) © 2021 The Authors
ER -