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

Medicina (Kaunas). 2023 Apr 29;59(5):863. doi: 10.3390/medicina59050863.

Abstract

Background and Objectives: Hydroxychloroquine (HCQ) combined with azithromycin (AZM) has been widely administered to patients with COVID-19 despite scientific controversies. In particular, the potential of prolong cardiac repolarization when using this combination has been discussed. Materials and Methods: We report a pragmatic and simple safety approach which we implemented among the first patients treated for COVID-19 in our center in early 2020. Treatment contraindications were the presence of severe structural or electrical heart disease, baseline corrected QT interval (QTc) > 500 ms, hypokalemia, or other drugs prolonging QTc that could not be interrupted. Electrocardiogram and QTc was evaluated at admission and re-evaluated after 48 h of the initial prescription. Results: Among the 424 consecutive adult patients (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 the 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 2 days of treatment (p = 0.003). QTc prolongation was particularly observed in female outpatients <65 years old without cardiovascular disease. 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, it shows that a simple initial assessment of patient medical history, electrocardiogram (ECG), and kalemia identifies contraindicated patients and enables the safe treatment of COVID-19 patients with HCQ-AZ. 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 applied.

Keywords: COVID-19; QTc interval; SARS-CoV-2; azithromycin; cardiac rhythm; hydroxychloroquine; safety; torsades de pointe.

MeSH terms

  • Adult
  • Aged
  • Azithromycin / adverse effects
  • COVID-19 Drug Treatment
  • COVID-19*
  • Electrocardiography / methods
  • Female
  • Humans
  • Hydroxychloroquine / adverse effects
  • Long QT Syndrome* / chemically induced
  • Middle Aged
  • SARS-CoV-2

Substances

  • Hydroxychloroquine
  • Azithromycin

Grants and funding

This work was performed by academic doctors working in the IHU Mediterranee Infection and in the Assistance Publique—Hôpitaux de Marseille, France. The IHU Mediterranee Infection was funded by the French government and benefited from a grant from Agence Nationale de la Recherche: ANR-15-CE36-0004-01 and by ANR Investissements d’avenir, Mediterranee infection 10-IAHU-03.