Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil
Arquivos Brasileiros de Cardiologia, doi:10.36660/abc.20220935
Background: Despite no evidence showing benefits of hydroxychloroquine and chloroquine with or without azithromycin for COVID-19 treatment, these medications have been largely prescribed in Brazil. Objectives: To assess outcomes, including in-hospital mortality, electrocardiographic abnormalities, hospital length-of-stay, admission to the intensive care unit, and need for dialysis and mechanical ventilation, in hospitalized COVID-19 patients who received chloroquine or hydroxychloroquine, and to compare outcomes between those patients and their matched controls. Methods: A retrospective multicenter cohort study that included consecutive laboratory-confirmed COVID-19 patients from 37 Brazilian hospitals from March to September 2020. Propensity score was used to select matching controls by age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid. A p-value <0.05 was considered statistically significant. Results: From 7,850 COVID-19 patients, 673 (8.6%) received hydroxychloroquine and 67 (0.9%) chloroquine. The median age in the study group was 60 years (46 -71) and 59.1% were women. During hospitalization, 3.2% of patients presented side effects and 2.2% required therapy discontinuation. Electrocardiographic abnormalities were more prevalent in the chloroquine/hydroxychloroquine group (13.2% vs. 8.2%, p=0.01), and the long corrected QT interval was the main difference (3.6% vs. 0.4%, p<0.001). The median hospital length of stay was longer in the HCQ/CQ + AZT group than in controls (9.0 [5.0, 18.0] vs. 8.0 [4.0, 14.0] days). There was no statistical differences between groups in intensive care unit admission (35.1% vs. 32.0%; p=0.282), invasive mechanical ventilation support (27.0% vs. 22.3%; p=0.074) or mortality (18.9% vs. 18.0%; p=0.682). Conclusion: COVID-19 patients treated with chloroquine or hydroxychloroquine had a longer hospital length of stay, when compared to matched controls. Intensive care unit admission, invasive mechanical ventilation, dialysis and inhospital mortality were similar.
Potential conflict of interest No potential conflict of interest relevant to this article was reported.
Sources of funding
Study association This study is not associated with any thesis or dissertation work.
Ethics approval and consent to participate This study was approved by the Comitê Nacional de Ética em Pesquisa under the protocol number CAAE 30350820.5.1001.0008. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013.
Axfors, Schmitt, Janiaud, Van't Hooft, Abd-Elsalam et al., Mortality Outcomes with Hydroxychloroquine and Chloroquine in COVID-19 from an International Collaborative Meta-Analysis of Randomized Trials, Nat Commun, doi:10.1038/s41467-021-22446-z
Brasil, Fundamentação e decisão Acerca das Diretrizes Terapêuticas para o Tratamento Farmacológico da COVID-19 (Hospitalar e Ambulatorial)
Cavalcanti, Zampieri, Rosa, Azevedo, Veiga et al., Hydroxychloroquine with or without Azithromycin in Mildto-Moderate Covid-19, N Engl J Med, doi:10.1056/NEJMoa2019014
Chi, Montazerin, Lee, Kazmi, Shojaei et al., Effect of Azithromycin and Hydroxychloroquine in Patients Hospitalized with COVID-19: Network Meta-Analysis of Randomized Controlled Trials, J Med Virol, doi:10.1002/jmv.27259
Chivese, Musa, Hindy, Al-Wattary, Badran et al., Efficacy of Chloroquine and Hydroxychloroquine in Treating COVID-19 Infection: A Meta-Review of Systematic Reviews and an Updated Meta-Analysis, Travel Med Infect Dis, doi:10.1016/j.tmaid.2021.102135
Diaz-Arocutipa, Brañez-Condorena, Hernandez, QTc Prolongation in COVID-19 Patients Treated with Hydroxychloroquine, Chloroquine, Azithromycin, or Lopinavir/Ritonavir: A Systematic Review and Meta-Analysis, Pharmacoepidemiol Drug Saf, doi:10.1002/pds.5234
Elavarasi, Prasad, Seth, Sahoo, Madan et al., Chloroquine and Hydroxychloroquine for the Treatment of COVID-19: a Systematic Review and Meta-analysis, J Gen Intern Med, doi:10.1007/s11606-020-06146-w
Ferreira, Beranger, Sampaio, Mansur, Filho et al., Outcomes Associated with Hydroxychloroquine and Ivermectin in Hospitalized Patients with COVID-19: A Single-Center Experience, Rev Assoc Med Bras, doi:10.1590/1806-9282.20210661
Fiolet, Guihur, Rebeaud, Mulot, Peiffer-Smadja et al., Effect of Hydroxychloroquine with or Without Azithromycin on the Mortality of Coronavirus Disease 2019 (COVID-19) Patients: A Systematic Review and Meta-Analysis, Clin Microbiol Infect, doi:10.1016/j.cmi.2020.08.022
Ghazy, Almaghraby, Shaaban, Kamal, Beshir et al., A Systematic Review and Meta-Analysis on Chloroquine and Hydroxychloroquine as Monotherapy or Combined with Azithromycin in COVID-19 Treatment, Sci Rep, doi:10.1038/s41598-020-77748-x
Group; Horby, Mafham, Linsell, Bell, Staplin, Effect of Hydroxychloroquine in Hospitalized Patients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2022926
Harris, Taylor, Minor, Elliott, Fernandez et al., The REDCap Consortium: Building an International Community of Software Platform Partners, J Biomed Inform, doi:10.1016/j.jbi.2019.103208
I B Á Ñ E Z S , M A R T Í N E Z O, Va l e n z u e l a F, S i l v a F, Va l e n z u e l a O. Hydroxychloroquine and Chloroquine in COVID-19: Should They be Used as Standard Therapy?, Clin Rheumatol, doi:10.1007/s10067-020-05202-4
Kashour, Riaz, Garbati, Aldosary, Tlayjeh et al., Efficacy of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-Analysis, J Antimicrob Chemother, doi:10.1093/jac/dkaa403
Marcolino, Figueira, Santos, Cardoso, Ribeiro et al., The Experience of a Sustainable Large Scale Brazilian Telehealth Network, Telemed J E Health, doi:10.1089/tmj.2015.0234
Marcolino, Ziegelmann, Souza-Silva, Nascimento, Oliveira et al., Clinical Characteristics and Outcomes of Patients Hospitalized with COVID-19 in Brazil: Results from the Brazilian COVID-19 Registry, Int J Infect Dis, doi:10.1016/j.ijid.2021.01.019
Mgt, Bicalho, Nogueira, Guimarães-Júnior, Aguiar et al., This is an open-access article distributed under the terms of the Creative Commons Attribution License *Supplemental Materials For additional information
Nascimento, Paixão, Tonaco, Alves, Peixoto et al., Clinical and Electrocardiographic Outcomes Evaluated by Telemedicine of Outpatients with Clinical Suspicion of COVID-19 Treated with Chloroquine Compounds in Brazil †, Front Cardiovasc Med, doi:10.3389/fcvm.2023.1028398
Pan, Peto, Henao-Restrepo, Preziosi, Sathiyamoorthy, Repurposed Antiviral Drugs for Covid-19 -Interim WHO Solidarity Trial Results, N Engl J Med, doi:10.1056/NEJMoa2023184
Rosa, Cavalcanti, Azevedo, Veiga, Souza et al., Association between Acute Disease Severity and One-Year Quality of Life among Post-Hospitalisation COVID-19 Patients: Coalition VII Prospective Cohort Study, Intensive Care Med, doi:10.1007/s00134-022-06953-1
Satarker, Ahuja, Banerjee, Balaji, Dogra et al., Hydroxychloroquine in COVID-19: Potential Mechanism of Action Against SARS-CoV-2, Curr Pharmacol Rep, doi:10.1007/s40495-020-00231-8
Von Elm, Altman, Egger, Pocock, Gøtzsche et al., Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies, BMJ, doi:10.1136/bmj.39335.541782