Systematic review and meta-analysis of the safety of chloroquine and hydroxychloroquine from randomized controlled trials on malarial and non-malarial conditions

Author(s):Show less -

Botelho, Mayra Souza ^[1] ; Bolfi, Fernanda ^[1] ; Occhiuto Ferreira Leite, Renata Giacomini ^[1] ; Ferreira Leite, Mauro Salles ^[1] ; Banzato, Luisa Rocco ^[1] ; Soares, Luiza Teixeira ^[1] ; Felicio Olivatti, Thaina Oliveira ^[1] ; Mangolim, Amanda Sampaio ^[1] ; Kazan Oliveira, Flavia Ramos ^[1] ; Fernandes Abbade, Luciana Patricia ^[2] ; Abbade, Joelcio Francisco ^[3] ; Monteiro de Barros Almeida, Ricardo Augusto ^[2] ; Correa Galendi, Julia Simoes ^{[4, 5]} ; Thabane, Lehana ^{[6, 7, 8]} ; Nunes-Nogueira, Vania dos Santos ^[1]

Affiliation

^[1] Sao Paulo State Univ UNESP, Med Sch, Dept Internal Med, Sao Paulo - Brazil

^[2] Sao Paulo State Univ UNESP, Med Sch, Dept Infect Dis Dermatol Imaging Diag & Radiother, Sao Paulo - Brazil

^[3] Sao Paulo State Univ UNESP, Med Sch, Dept Gynecol & Obstet, Sao Paulo - Brazil

^[4] Univ Cologne, Fac Med, Inst Hlth Econ & Clin Epidemiol, Cologne - Germany

^[5] Univ Cologne, Univ Hosp Cologne, Cologne - Germany

^[6] McMaster Univ, Dept Hlth Res Methods Evidence & Impact, Hamilton, ON - Canada

^[7] St Josephs Healthcare Hamilton, Biostat Unit, Hamilton, ON - Canada

^[8] Univ Johannesburg, Fac Hlth Sci, Johannesburg - South Africa

• Document type: Review article
• Source: SYSTEMATIC REVIEWS; v. 10, n. 1 NOV 4 2021.
• Web of Science Citations: 0

Abstract

Background: Despite the expectations regarding the effectiveness of chloroquine (CQ) and hydroxychloroquine (HCQ) for coronavirus disease (COVID-19) management, concerns about their adverse events have remained. Objectives: The objective of this systematic review was to evaluate the safety of CQ and HCQ from malarial and non-malarial randomized clinical trials (RCTs). Methods: The primary outcomes were the frequencies of serious adverse events (SAEs), retinopathy, and cardiac complications. Search strategies were applied to MEDLINE, EMBASE, LILACS, CENTRAL, Scopus, and Trip databases. We used a random-effects model to pool results across studies and Peto's one-step odds ratio (OR) for event rates below 1%. Both-armed zero-event studies were excluded from the meta-analyses. We used the Grading of Recommendations Assessment, Development, and Evaluation system to evaluate the certainty of evidence. Results: One hundred and six RCTs were included. We found no significant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95% confidence interval {[}CI]: 0.76-1.26, 33 trials, 15,942 participants, moderate certainty of evidence). However, there was a moderate certainty of evidence that CQ/HCQ increases the incidence of cardiac complications (RR: 1.62, 95% CI: 1.10-2.38, 16 trials, 9908 participants). No clear relationship was observed between CQ/HCQ and retinopathy (OR: 1.63, 95% CI: -0.4-6.57, 5 trials, 344 participants, very low certainty of evidence). Conclusions: CQ and HCQ probably do not increase SAEs, with low frequency of these adverse events on malarial and non-malarial conditions. However, they may increase cardiac complications especially in patients with COVID-19. No clear effect of their use on the incidence of retinopathy was observed. (AU)

• FAPESP's process: 18/11836-6 - Effectiveness of Testosterone Therapy in Obese Men with Low Testosterone Levels, for Losing Weight, Controlling Obesity Complications, and Preventing Cardiovascular Events: A Systematic Review of Randomized Controlled Trials
• Grantee: Vania dos Santos Nunes Nogueira
• Support Opportunities: Regular Research Grants