Background: Hydroxychloroquine (HCQ) was proposed as a potential treatment for COVID-19, but its association with mortality is not well characterized. We conducted two meta-analyses to evaluate the association between HCQ (with or without azithromycin (AZM)) and total mortality in COVID-19 patients.
Methods: Articles were retrieved until November 10th, 2020 by searching in seven databases. Data were combined using the general variance-based method.
Results: A total of 27 articles were found (N=44,684 patients, including N=7,803 from 5 randomized clinical trials (RCTs)). Overall, the use of HCQ was associated with a 22% lower mortality risk (pooled risk ratio: 0.78, 95%CI: 0.67 to 0.91; I2=80%, random effects). This association was found reversed when pooling only RCTs (16.7% of the overall weight; pooled risk ratio: 1.11, 0.99 to 1.24) or studies in which daily dose >400 mg or total dose >4,400 mg were used (pooled risk ratio: 1.10, 95%CI: 0.99 to 1.23 in both cases). Overall, HCQ+AZM (10 studies) was also associated with 28% lower mortality risk, but the uncertainty was large (95%CI: 0.48 to 1.08; P=0.11). The use of HCQ was not associated with severe adverse events.
Conclusions: HCQ use was not associated with mortality reduction in COVID-19 patients when 5 RCTs only were evaluated, while a 9% to 33% reduced mortality was observed when observational studies were also included. The association was mainly apparent in studies that used lower doses of HCQ. These findings can help to disentangle the debate on HCQ use in COVID-19.