Gueta I, Loebstein R, Markovits N, Kamari Y, Halkin H, Livni G, Yarden-Bilavsky H
Institute of Clinical Pharmacology and Toxicology, Sheba Medical Center, Tel Hashomer, 52621, Ramat Gan, Israel.
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Eur J Clin Pharmacol. 2017 Sep;73(9):1181-1185. doi: 10.1007/s00228-017-2284-5. Epub 2017 Jun 17.
The purpose of this study is to determine the rate of QTcP and associated risk factors in patients treated with voriconazole.
We conducted a retrospective chart review of all patients treated with voriconazole in a large tertiary center between 2009 and 2015, using paired comparison of QTc intervals on and off voriconazole treatment, adjusted for comorbidities, electrolyte abnormalities, and concurrent medications.
Fifty-four patients were included, of whom 53 were diagnosed with oncologic/hemato-oncologic disease. Mean QTc during voriconazole therapy (448.0 ± 52.9 msec) was significantly longer compared to QTc off voriconazole (421.8 ± 42.2 msec; p = 0.002). QTcP ≥30 msec and ≥60 msec was demonstrated in 43% (23 patients) and 28% (15 patients), respectively. Multivariate analysis showed that QTcP was significantly associated with baseline QTc ≥ 450 msec (upper QTc quartile) (p < 0.01) and low serum potassium levels (p < 0.01). Contrarily, no significant association was found between mean voriconazole daily and cumulative dose and QTcP.
Our findings indicate that hemato-oncologic patients treated with voriconazole are at increased risk for QTcP, especially in the presence of baseline QTc ≥ 450 msec and low serum potassium levels.
本研究旨在确定接受伏立康唑治疗的患者中QTcP的发生率及相关危险因素。
我们对2009年至2015年期间在一家大型三级中心接受伏立康唑治疗的所有患者进行了回顾性病历审查，采用配对比较伏立康唑治疗期间和治疗前的QTc间期，并对合并症、电解质异常和同时使用的药物进行了调整。
共纳入54例患者，其中53例被诊断患有肿瘤/血液肿瘤疾病。伏立康唑治疗期间的平均QTc（448.0±52.9毫秒）显著长于未使用伏立康唑时的QTc（421.8±42.2毫秒；p = 0.002）。QTcP≥30毫秒和≥60毫秒的情况分别在43%（23例患者）和28%（15例患者）中出现。多变量分析显示，QTcP与基线QTc≥450毫秒（QTc上四分位数）（p < 0.01）和低血钾水平（p < 0.01）显著相关。相反，未发现伏立康唑每日平均剂量和累积剂量与QTcP之间存在显著关联。
我们的研究结果表明，接受伏立康唑治疗的血液肿瘤患者发生QTcP的风险增加，尤其是在基线QTc≥450毫秒和低血钾水平的情况下。
