Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Drug Safety Research Center, Facultad de Medicina Humana, Universidad de San Martín de Porres. Hospital Almenara, ESSALUD, Lima, Perú.
Clinical Pharmacology Department, Vall d'Hebron Hospital, Barcelona, Spain.
Int J Antimicrob Agents. 2020 Dec;56(6):106212. doi: 10.1016/j.ijantimicag.2020.106212. Epub 2020 Oct 24.
Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown. Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ. Data Sources PubMed, EMBASE, Google Scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv, Research Square) were searched for studies published between December 2019 and June 30, 2020. Methods Effect statistics were pooled using random effects. The quality of observational studies and randomized controlled trials was appraised with STROBE and the Cochrane Risk of Bias Assessment tools, respectively. Outcomes Critical LQT was defined as: (1) maximum QT corrected (QTc)≥500 ms (if QRS<120 ms) or QTc≥550 ms (if QRS≥120 ms), and (2) QTc increase ≥60 ms. Results In the 28 studies included (n=9124), the frequency of LQT during HCQ treatment was 6.7% (95% confidence interval [CI]: 3.7-10.2). In 20 studies (n=7825), patients were also taking other QT-prolonging drugs. The frequency of LQT in the other 8 studies (n=1299) was 1.7% (95% CI: 0.3-3.9). Twenty studies (n=6869) reported HCQ discontinuation due to LQT, with a frequency of 3.7% (95% CI: 1.5-6.6). The frequency of ventricular arrhythmias during HCQ treatment was 1.68% (127/7539) and that of arrhythmogenic death was 0.69% (39/5648). Torsades de Pointes occurred in 0.06% (3/5066). Patients aged >60 years were at highest risk of HCQ-associated LQT (P<0.001). Conclusions HCQ-associated cardiotoxicity in SARS-CoV-2 patients is uncommon but requires ECG monitoring, particularly in those aged >60 years and/or taking other QT-prolonging drugs.
介绍 羟氯喹 (HCQ) 已被提议作为 SARS-CoV-2 的治疗方法，但在使用过程中出现长 QT (LQT) 的频率尚不清楚。 目的 对 SARS-CoV-2 感染患者使用 HCQ 治疗时发生 LQT 的频率进行荟萃分析。 数据来源 检索了 2019 年 12 月至 2020 年 6 月 30 日期间发表的来自 PubMed、EMBASE、Google Scholar、Cochrane 系统评价数据库和预印本服务器（medRxiv、Research Square）的研究。 方法 使用随机效应汇总效应统计数据。分别使用 STROBE 和 Cochrane 偏倚风险评估工具评估观察性研究和随机对照试验的质量。 结果 在纳入的 28 项研究中（n=9124），HCQ 治疗期间 LQT 的发生率为 6.7%（95%置信区间[CI]：3.7-10.2）。在 20 项研究中（n=7825），患者还同时服用其他 QT 延长药物。在其余 8 项研究（n=1299）中，LQT 的发生率为 1.7%（95% CI：0.3-3.9）。20 项研究（n=6869）报告了因 LQT 而停用 HCQ，发生率为 3.7%（95% CI：1.5-6.6）。在 HCQ 治疗期间，室性心律失常的发生率为 1.68%（127/7539），心律失常性死亡的发生率为 0.69%（39/5648）。尖端扭转型室性心动过速的发生率为 0.06%（3/5066）。年龄 >60 岁的患者发生 HCQ 相关性 LQT 的风险最高（P<0.001）。 结论 SARS-CoV-2 患者中与 HCQ 相关的心脏毒性并不常见，但需要进行心电图监测，特别是年龄 >60 岁和/或正在服用其他 QT 延长药物的患者。
