Duijvelaar Erik, Vanhove Arthur, Schippers Job R, Smeele Patrick J, de Man Frances S, Pinto Yigal, Aman Jurjan, Bogaard Harm Jan
Amsterdam UMC, location VUMC, Vrije Universiteit Amsterdam, Department of Pulmonary Medicine, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands; and.
Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology.
J Cardiovasc Pharmacol. 2022 Dec 1;80(6):783-791. doi: 10.1097/FJC.0000000000001344.
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%.
尽管先前的研究支持伊马替尼对新冠肺炎住院患者呼吸状况的临床益处，但潜在的心脏毒性可能会限制其临床应用。本研究旨在调查伊马替尼在新冠肺炎中的心脏安全性。在CounterCOVID研究中，385例新冠肺炎住院低氧血症患者被随机分配，以1:1的比例接受为期10天的口服伊马替尼或安慰剂治疗。校正QT间期（QTc）>500毫秒或左心室射血分数<40%的患者被排除。对严重心脏不良事件进行28天监测或直至死亡发生。在最初10天内反复评估心电图测量值和心脏生物标志物。共发生36例严重心脏事件，两个治疗组的发生率相似。在计算机生成的Bazett法、人工解读的Bazett法或Fridericia法解读的QTc方面未观察到差异。在其他心电图参数或血浆高敏心肌肌钙蛋白T（hs-cTnT）和脑钠肽N端前体（NT-proBNP）浓度方面未观察到临床相关改变。在入住重症监护病房的72例患者亚组中也观察到了类似的结果。在单变量和多变量线性混合模型中，伊马替尼治疗与QT间期持续时间、hs-cTnT或NT-proBNP水平无显著相关性。总之，伊马替尼治疗未导致更多心脏事件、QT间期延长或hs-cTnT或NT-proBNP水平改变。这表明，对于QTc持续时间小于500毫秒且左心室射血分数>40%的新冠肺炎住院患者，伊马替尼治疗是安全的。
