A combination of hydroxychloroquine (HCQ) and azithromycin (AZ) to treat patients with coronavirus disease 2019 (COVID-19) was found to prolong QTc interval without clinically affecting patients, according to a study published in Mayo Clinic Proceedings.

The use of an HCQ plus AZ regimen for the prevention of hypoxemic respiratory failure and death in patients with COVID-19 has received global attention, despite yet unproven efficacy.

A total of 50 consecutive patients (median age, 68 years; interquartile range [IQR], 53-81 years; 55.2% men) who received HCQ (600 mg/day for 10 days) in combination with AZ (500 mg on day 1, and 250 mg daily, on days-5) between March 18 and March 25, 2020 were enrolled in this study. Each patient received a 12-lead electrocardiogram (ECG) before treatment, 3 and 5 days after treatment initiation, and at discharge. In this cohort, 43% of the patients reported a history of cardiovascular disease (hypertension, 37%); diabetes, 17%).

Mean QTc was 408 ms (IQR, 343-478 ms) at baseline, and increased to 437 ms ([QR, 380-500 ms) at day 3 and to 456 ms (IQR, 397 ms-518 ms) at day 5. A total of 76% of patients presented short-term modifications of QTc duration (ie >30 ms). Premature treatment discontinuation due to prespecified QTc criteria was decided for 6 patients, leading to QTc normalization in 5 of them. None of the patients died or had cardiac arrhythmic events.


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Limitations of the study include a limited number of patients and the lack of ECG monitoring data after discharge.

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“[W]e did not observe any clinically relevant consequence of these transitory modifications,” noted the study authors. “[W]hen patients are treated with the combination of hydroxychloroquine and azithromycin, cardiac monitoring should be regularly performed and hospital settings allow to do it in safe conditions.”

Reference

Voisin O, Lorc’h El, Mahe A, Azria A, Borie MF, Hubert S. Acute QT interval modifications during hydroxychloroquine-azithromycin treatment in the context of COVID-19 infection (published online May 11, 2020). Mayo Clin Proc. doi:10.1016/j.mayocp.2020.05.005