Τίτλος:
Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Felker, G.M.
McMurray, J.J.V.
Cleland, J.G.
O'Connor, C.M.
Teerlink, J.R.
Voors, A.A.
Belohlavek, J.
Böhm, M.
Borentain, M.
Bueno, H.
Cole, R.T.
DeSouza, M.M.
Ezekowitz, J.A.
Filippatos, G.
Lang, N.N.
Kessler, P.D.
Martinez, F.A.
Mebazaa, A.
Metra, M.
Mosterd, A.
Pang, P.S.
Ponikowski, P.
Sato, N.
Seiffert, D.
Ye, J.
Περιοδικό:
JACC: Heart Failure
Εκδότης:
HANLEY & BELFUS-ELSEVIER INC
Λέξεις-κλειδιά:
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
DOI:
10.1016/j.jchf.2020.10.012
