Agstam Sourabh, Yadav Ashutosh, Kumar-M Praveen, Gupta Ankur
Department of Cardiology, VMMC & Safdarjung Hospital, New Delhi, India.
Department of Cardiology, Fortis Hospital, Mohali, Punjab, India.
Indian Pacing Electrophysiol J. 2021 Jan-Feb;21(1):36-43. doi: 10.1016/j.ipej.2020.10.002. Epub 2020 Oct 16.
Among many drugs that hold potential in COVID-19 pandemic, chloroquine (CQ), and its derivative hydroxychloroquine (HCQ) have generated unusual interest. With increasing usage, there has been growing concern about the prolongation of QTc interval and Torsades de Pointes (TdP) with HCQ, especially in combination with azithromycin.
This meta-analysis is planned to study the risk of QTc prolongation and Torsades de pointes (TdP) by a well-defined criterion for HCQ, CQ alone, and in combination with Azithromycin in patients with COVID-19.
A comprehensive literature search was made in two databases (PubMed, Embase). Three outcomes explored in the included studies were frequency of QTc > 500 ms (ms) or ΔQTc > 60 ms (Outcome 1), frequency of QTc > 500 ms (Outcome 2) and frequency of TdP (Outcome 3). Random effects method with inverse variance approach was used for computation of pooled summary and risk ratio.
A total of 13 studies comprising of 2138 patients were included in the final analysis. The pooled prevalence of outcome 1, outcome 2 and outcome 3 for HCQ, CQ with or without Azithromycin were 10.18% (5.59-17.82%, I - 92%), 10.22% (6.01-16.85%, I - 79%), and 0.72% (0.34-1.51, I - 0%) respectively. The prevalence of outcome 2 in subgroup analysis for HCQ and HCQ + Azithromycin was 7.25% (3.22-15.52, I - 59%) and 8.61% (4.52-15.79, I - 76%), respectively. The risk ratio (RR) for outcome 1 and outcome 2 between HCQ + Azithromycin and HCQ was 1.22 (0.77-1.93, I - 0%) & 1.51 (0.79-2.87, I - 13%), respectively and was not significant. Heterogeneity was noted statistically as well clinically (regimen types, patient numbers, study design, and outcome definition).
The use of HCQ/CQ is associated with a high prevalence of QTc prolongation. However, it is not associated with a high risk of TdP.
在众多对2019冠状病毒病大流行具有潜在作用的药物中，氯喹（CQ）及其衍生物羟氯喹（HCQ）引起了特别关注。随着其使用的增加，人们越来越担心羟氯喹会延长QTc间期并导致尖端扭转型室速（TdP），尤其是与阿奇霉素联合使用时。
本荟萃分析旨在依据明确标准研究新冠患者单独使用羟氯喹、氯喹以及二者与阿奇霉素联合使用时QTc延长和尖端扭转型室速（TdP）的风险。
在两个数据库（PubMed、Embase）中进行了全面的文献检索。纳入研究中探索的三个结果分别为QTc>500毫秒（ms）或ΔQTc>60毫秒的频率（结果1）、QTc>500毫秒的频率（结果2）以及尖端扭转型室速（TdP）的频率（结果3）。采用具有逆方差方法的随机效应模型来计算合并汇总和风险比。
最终分析纳入了13项研究，共2138例患者。羟氯喹、氯喹单独或联合阿奇霉素时结果1、结果2和结果3的合并患病率分别为10.18%（5.59 - 17.82%，I - 92%）、10.22%（6.01 - 16.85%，I - 79%）和0.72%（0.34 - 1.51，I - 0%）。羟氯喹和羟氯喹+阿奇霉素亚组分析中结果2的患病率分别为7.25%（3.22 - 15.52，I - 59%）和8.61%（4.52 - 15.79，I - 76%）。羟氯喹+阿奇霉素与羟氯喹相比结果1和结果2的风险比（RR）分别为1.22（0.77 - 1.93，I - 0%）和1.51（0.79 - 2.87，I - 13%），均无统计学意义。在统计学及临床方面（治疗方案类型、患者数量、研究设计和结果定义）均发现了异质性。
使用羟氯喹/氯喹与QTc延长的高患病率相关。然而，它与尖端扭转型室速的高风险无关。
