Systematic Review and Meta-analysis of the Safety of Chloroquine and Hydroxychloroquine on Malarial and Nonmalarial Conditions

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  • Presentation type: Apresentação Oral
  • Track: 5. ATS em tempos de COVID
  • Keywords: Chloroquine; hydroxychloroquine; COVID-19; systematic review;
  • 1 Universidade Estadual Paulista “Júlio de Mesquita Filho” - Campus Botucatu
  • 2 Faculdade de Medicina de Botucatu - Universidade Estadual Paulista- UNESP-
  • 3 University Hospital of Cologne
  • 4 McMaster University

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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 random-effects model to pool results across studies and Peto 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: Ninety-two RCTs were included. We found no signicant difference between CQ/HCQ and control (placebo or non-CQ/HCQ) in the frequency of SAEs (OR: 0.98, 95 % condence interval [CI]: 0.71–1.36, 25 trials, 11,605 participants, moderate certainty of evidence). 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). There was a low certainty of evidence of the effect of CQ/HCQ versus control on cardiac complications (Relative risk: 1.48, 95 % CI: 1.1–1.98, 8 trials, 5,970 participants). Conclusions: CQ and HCQ might be safe, with low frequency of SAEs on malarial and non-malarial conditions. No clear effect of their use on the incidence of retinopathy and cardiac complications was observed. PROSPERO Registration: CRD42020177818 Funding: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.

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