Browsing by Author "Belohlavek, Jan"

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    Effects of a Novel Nitroxyl Donor in Acute Heart Failure: The STAND-UP AHF Study
    (Elsevier, 2021) Felker, G. Michael; McMurray, John J. V.; Cleland, John G.; O’Connor, Christopher M.; Teerlink, John R.; Voors, Adriaan A.; Belohlavek, Jan; Böhm, Michael; Borentain, Maria; Bueno, Hector; Cole, Robert T.; DeSouza, Mary M.; Ezekowitz, Justin A.; Filippatos, Gerasimos; Lang, Ninian N.; Kessler, Paul D.; Martinez, Felipe A.; Mebazaa, Alex; Metra, Marco; Mosterd, Arend; Pang, Peter S.; Ponikowski, Piotr; Sato, Naoki; Seiffert, Dietmar; Ye, June; Emergency Medicine, School of Medicine
    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.