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

Million et al., Preprints, doi:10.20944/preprints202303.0325.v1, Mar 2023

HCQ for COVID-19

1st treatment shown to reduce risk in March 2020, now with p < 0.0000000001 from 426 studies, used in 59 countries.

No treatment is 100% effective.
Protocols combine treatments.

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.
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.
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DOI record: { "DOI": "10.20944/preprints202303.0325.v1", "URL": "http://dx.doi.org/10.20944/preprints202303.0325.v1", "abstract": "<jats:p>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) &amp;gt;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 &amp;plusmn; 16.1 years; 216 women). Patients were followed in conventional wards (21.5%) or in a day-care unit (78.5%). 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 &amp;plusmn; 25.4 ms after two days (p=0.003). Ten patients (2.4%) developed QTc prolongation &amp;gt;60 ms, and none had QTc &amp;gt;500 ms. Conclusions This report do 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 kalaemia identifies contraindicated patients and enables the safe treatment by HCQ-AZ of COVID-19 patients. QT-prolonging anti-infective drugs can be used safely in acute life-threatening infections, provided that a strict protocol and close collaboration between infectious disease specialists and rhythmologists are followed.</jats:p>", "accepted": { "date-parts": [ [ 2023, 3, 15 ] ] }, "author": [ { "ORCID": "http://orcid.org/0000-0002-5556-6947", "affiliation": [], "authenticated-orcid": false, "family": "Million", "given": "Matthieu", "sequence": "first" }, { "affiliation": [], "family": "Lagier", "given": "Jean-Christophe", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-7007-7247", "affiliation": [], "authenticated-orcid": false, "family": "Hourdain", "given": "Jérôme", "sequence": "additional" }, { "affiliation": [], "family": "Franceschi", "given": "Frédéric", "sequence": "additional" }, { "affiliation": [], "family": "Deharo", "given": "Jean-Claude", "sequence": "additional" }, { "affiliation": [], "family": "Parola", "given": "Philippe", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-6125-2805", "affiliation": [], "authenticated-orcid": false, "family": "Brouqui", "given": "Philippe", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2023, 3, 20 ] ], "date-time": "2023-03-20T00:38:56Z", "timestamp": 1679272736000 }, "deposited": { "date-parts": [ [ 2023, 3, 20 ] ], "date-time": "2023-03-20T00:39:18Z", "timestamp": 1679272758000 }, "group-title": "LIFE SCIENCES", "indexed": { "date-parts": [ [ 2023, 3, 20 ] ], "date-time": "2023-03-20T01:11:26Z", "timestamp": 1679274686757 }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2023, 3, 17 ] ] }, "license": [ { "URL": "http://creativecommons.org/licenses/by/4.0", "content-version": "unspecified", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 3, 17 ] ], "date-time": "2023-03-17T00:00:00Z", "timestamp": 1679011200000 } } ], "member": "1968", "original-title": [], "posted": { "date-parts": [ [ 2023, 3, 17 ] ] }, "prefix": "10.20944", "published": { "date-parts": [ [ 2023, 3, 17 ] ] }, "publisher": "MDPI AG", "reference-count": 0, "references-count": 0, "relation": {}, "resource": { "primary": { "URL": "https://www.preprints.org/manuscript/202303.0325/v1" } }, "score": 1, "short-title": [], "source": "Crossref", "subtitle": [], "subtype": "preprint", "title": "Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients", "type": "posted-content" }