Efficacy of chloroquine or hydroxychloroquine in COVID-19 patients: a systematic review and meta-analysis

Objectives Clinical studies of chloroquine (CQ) and hydroxychloroquine (HCQ) in COVID-19 disease reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin on outcomes of COVID-19 patients. Methods We searched multiple databases, preprints and grey literature up to 17 July 2020. We pooled only adjusted-effect estimates of mortality using a random-effect model. We summarized the effect of CQ or HCQ on viral clearance, ICU admission/mechanical ventilation and hospitalization. Results Seven randomized clinical trials (RCTs) and 14 cohort studies were included (20 979 patients). Thirteen studies (1 RCT and 12 cohort studies) with 15 938 hospitalized patients examined the effect of HCQ on short-term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96–1.15, I2 = 0%). Six cohort studies examined the effect of the HCQ+azithromycin combination with a pooled adjusted OR of 1.32 (95% CI 1.00–1.75, I2 = 68.1%). Two cohort studies and four RCTs found no effect of HCQ on viral clearance. One small RCT demonstrated improved viral clearance with CQ and HCQ. Three cohort studies found that HCQ had no significant effect on mechanical ventilation/ICU admission. Two RCTs found no effect for HCQ on hospitalization risk in outpatients with COVID-19. Conclusions Moderate certainty evidence suggests that HCQ, with or without azithromycin, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19 or risk of hospitalization in outpatients with COVID-19

Cardiac toxicity of chloroquine or hydroxychloroquine in patients With COVID-19: A systematic review and meta-regression analysis

Objective To systematically review the literature and to estimate the risk of chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in patients with coronavirus disease 2019 (COVID-19). Methods We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled patients with COVID-19 treated with CQ or HCQ, with or without azithromycin, and reported on cardiac toxic effects. We performed a meta-analysis using the arcsine transformation of the different incidences. Results A total of 19 studies with a total of 5652 patients were included. The pooled incidence of torsades de pointes arrhythmia, ventricular tachycardia, or cardiac arrest was 3 per 1000 (95% CI, 0-21; I2=96%) in 18 studies with 3725 patients. Among 13 studies of 4334 patients, the pooled incidence of discontinuation of CQ or HCQ due to prolonged QTc or arrhythmias was 5% (95% CI, 1-11; I2=98%). The pooled incidence of change in QTc from baseline of 60 milliseconds or more or QTc of 500 milliseconds or more was 9% (95% CI, 3-17; I2=97%). Mean or median age, coronary artery disease, hypertension, diabetes, concomitant QT-prolonging medications, intensive care unit admission, and severity of illness in the study populations explained between-studies heterogeneity. Conclusion Treatment of patients with COVID-19 with CQ or HCQ is associated with an important risk of drug-induced QT prolongation and relatively higher incidence of torsades de pointes, ventricular tachycardia, or cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. Patients with COVID-19 who are treated with antimalarials for other indications should be adequately monitored

The Cardiac Toxicity of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-regression Analysis.

Objective: To systematically review the literature and estimate the risk of Chloroquine (CQ) and hydroxychloroquine (HCQ) cardiac toxicity in COVID-19 patients. Methods: We searched multiple data sources including PubMed/MEDLINE, Ovid Embase, Ovid EBM Reviews, Scopus, and Web of Science, and medrxiv.org from November 2019 through May 27, 2020. We included studies that enrolled COVID-19 patients treated with CQ or HCQ, with or without azithromycin and reported on cardiac toxicities. We performed a meta-analysis using the arcsine transformation of the different incidences. Results: A total of 19 studies with a total of 5652 patients were included. The pooled incidence of TdP arrhythmia or VT or cardiac arrest was 3 per 1000, 95% CI (0-21), I Conclusions: Treatment of COVID-19 patients with CQ or HCQ is associated with a significant risk of drug-induced QT prolongation and relatively higher incidence of TdP/VT/cardiac arrest. Therefore, these agents should not be used routinely in the management of COVID-19 disease. COVID-19 patients who are treated with antimalarials for other indications should be adequately monitored