Cardiac Safety of Imatinib for the Treatment of COVID-19: A Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial.

Autor:	Duijvelaar E; Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands; and., Vanhove A; Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands; and., Schippers JR; Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands; and., Smeele PJ; Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands; and., de Man FS; Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands; and., Pinto Y; Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology., Aman J; Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands; and., Bogaard HJ; Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands; and.
Jazyk:	angličtina
Zdroj:	Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2022 Dec 01; Vol. 80 (6), pp. 783-791. Date of Electronic Publication: 2022 Dec 01.
DOI:	10.1097/FJC.0000000000001344
Abstrakt:	Abstract: Although previous studies support the clinical benefit of imatinib regarding respiratory status in hospitalized patients with COVID-19, potential cardiotoxicity may limit its clinical application. This study aimed to investigate the cardiac safety of imatinib in COVID-19. In the CounterCOVID study, 385 hospitalized hypoxemic patients with COVID-19 were randomly assigned to receive 10 days of oral imatinib or placebo in a 1:1 ratio. Patients with a corrected QT interval (QTc) >500 ms or left ventricular ejection fraction <40% were excluded. Severe cardiac adverse events were monitored for 28 days or until death occurred. Electrocardiogram measurements and cardiac biomarkers were assessed repeatedly during the first 10 days. A total of 36 severe cardiac events occurred, with a similar incidence in both treatment groups. No differences were observed in the computer-generated Bazett, manually interpreted Bazett, or Fridericia-interpreted QTcs. No clinically relevant alterations in other electrocardiogram parameters or plasma high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations were observed. Similar findings were observed in a subgroup of 72 patients admitted to the intensive care unit. In the univariate and multivariable linear mixed models, treatment with imatinib was not significantly associated with QT interval duration, hs-cTnT, or NT-proBNP levels. In conclusion, imatinib treatment did not result in more cardiac events, QT interval prolongation, or altered hs-cTnT or NT-proBNP levels. This suggests that treatment with imatinib is safe in hospitalized patients with COVID-19 with a QTc duration of less than 500 ms and left ventricular ejection fraction >40%. Competing Interests: J. Aman and A. Vonk Noordegraaf are inventors of a patent (WO2012150857A1, 2011) covering protection against endothelial barrier dysfunction through inhibition of the tyrosine kinase Abl-related gene (Arg). The remaining authors report no conflicts of interest. (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze:	MEDLINE
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