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Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients

Million et al., Preprints, doi:10.20944/preprints202303.0325.v1
Mar 2023  
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HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 419 studies, recognized in 46 countries.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 109 treatments. c19hcq.org
Retrospective 424 consecutive patients in France showing that HCQ+AZ treatment was safe for early stage COVID-19 treatment with the protocol used, which excluded 11 patients for contraindications.
Treatment contraindications were the presence of severe structural or electrical heart disease, QTc >500ms, hypokalaemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 hours of the initial prescription.
Million et al., 17 Mar 2023, retrospective, France, preprint, mean age 46.3, 7 authors, study period 3 March, 2020 - 5 April, 2020. Contact: matthieumillion@gmail.com.
This PaperHCQAll
Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients
Matthieu Million, Jean-Christophe Lagier, Jérôme Hourdain, Frédéric Franceschi, Jean-Claude Deharo, Philippe Parola, Philippe Brouqui
doi:10.20944/preprints202303.0325.v1
Background: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular the potential to prolong cardiac repolarisation by using this combination has been discussed. Materials and methods: We report a pragmatic and simple safety approach which we implemented in the first patients treated for COVID-19 in our center early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) >500 ms, hypokalaemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 hours of the initial prescription. Results: Among 424 consecutive adults (mean age 46.3 ± 16.1 years; 216 women), 21.5% patients were followed in conventional wards and 78.5% in a day-care unit. A total of 11 patients (2.6%) had contraindications to HCQ-AZ combination. In the remaining 413 treated patients, there were no arrhythmic events in any patient during the 10-day treatment regimen. QTc was slightly but statistically significantly prolonged by 3.75 ± 25.4 ms after two days (p=0.003). Ten patients (2.4%) developed QTc prolongation >60 ms, and none had QTc >500 ms. Conclusions: This report does not aim to contribute to knowledge of the efficacy of treating COVID-19 with HCQ-AZ. However, a simple initial assessment of patient medical history, ECG and kalemia identifies contraindicated patients and enables the safe treatment by HCQ-AZ of COVID-19 patients. QTprolonging anti-infective drugs can be used safely in acute lifethreatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists is applied. Disclaimer/Publisher's Note: The statements, opinions, and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions, or products referred to in the content.
Conflicts of Interest: None of the authors declare have any conflicts of interest to declare.
References
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Costedoat-Chalumeau, Hulot, Amoura, Leroux, Lechat et al., Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases, Rheumatology
Fossa, Wisialowski, Duncan, Deng, Dunne, Azithromycin/Chloroquine combination does not increase cardiac instability despite an increase in monophasic action potential duration in the anesthetized guinea pig, Am J Trop Med Hyg
Gasperetti, Biffi, Duru, Schiavone, Ziacchi et al., Arrhythmic safety of hydroxychloroquine in COVID-19 patients from different clinical settings, Europace, doi:10.1093/europace/euaa216
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