ABSTRACT

Background: Hydroxychloroquine (HCQ) was proposed as potential treatment for COVID-19, but its association with mortality is unclear. We reviewed published literature for evidence of an association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients.

Methods: Articles were retrieved until April 29^th, 2021 by searching in seven databases. Data were combined using the general-variance-based method.

Results: A total of 25 cohort studies (N=41,339 patients) and 11 randomized clinical trials (RCTs; N=8,709) were found. The use of HCQ was not associated with mortality in meta-analysis of RCTs (pooled risk ratio (PRR): 1.08, 95%CI: 0.97-1.20; I²=0%), but it was associated with 20% lower mortality risk (PRR=0.80, 95%CI: 0.69-0.93; I²=80%) in pooling of cohort studies. The negative association with mortality was mainly apparent by pooling cohort studies that used lower doses of HCQ (≤400 mg/day; PRR=0.69, 95%CI: 0.57-0.87). Use of HCQ+AZM (11 studies) was associated with 25% non-statistically significant lower mortality risk (PPR=0.75; 0.51-1.10; P=0.15). Use of HCQ was not associated with severe adverse events (PRR=1.12, 95%CI: 0.88-1.44; I²=0%).

Conclusions: HCQ use was not associated with mortality in COVID-19 patients in pooling results from RCTs (high level of certainty of evidence), but it was associated with 20% mortality reduction when findings from observational studies were combined (low level of certainty of evidence). The reduction of mortality was mainly apparent in observational studies where lower doses of HCQ were used. These findings might help disentangling the debate on HCQ use in COVID-19.

 抽象的

背景：羟氯喹 (HCQ) 被提议作为 COVID-19 的潜在治疗方法，但其与死亡率的关系尚不清楚。我们回顾了已发表的文献，寻找 HCQ（加或不加阿奇霉素 (AZM)）与 COVID-19 患者总死亡率之间关联的证据。

方法：通过在七个数据库中检索截至2021年4月29^日的文章。使用基于一般方差的方法合并数据。

结果：共发现 25 项队列研究（N=41,339 名患者）和 11 项随机临床试验（RCT；N=8,709）。在 RCT 荟萃分析中，使用 HCQ 与死亡率无关（合并风险比 (PRR)：1.08，95%CI：0.97-1.20；I ² =0%），但与死亡风险降低 20% 相关(PRR=0.80, 95%CI: 0.69-0.93; I ² =80%) 队列研究汇总。通过使用较低剂量 HCQ（≤400 毫克/天；PRR=0.69，95%CI：0.57-0.87）的合并队列研究，与死亡率的负相关性主要明显。使用 HCQ+AZM（11 项研究）与 25% 的死亡率风险降低（PPR=0.75；0.51-1.10；P=0.15）相关，且死亡率风险无统计学意义。使用HCQ与严重不良事件无关（PRR=1.12，95%CI：0.88-1.44；I ² =0%）。

结论：根据 RCT 的汇总结果（证据质量高），HCQ 的使用与 COVID-19 患者的死亡率无关，但当结合观察性研究的结果时，HCQ 与死亡率降低 20% 相关（证据质量低）证据）。死亡率的降低主要体现在使用较低剂量 HCQ 的观察性研究中。这些发现可能有助于解开关于 HCQ 在 COVID-19 中使用的争论。