Hydroxychloroquine/Azithromycin Therapy and QT Prolongation in Hospitalized Patients with COVID-19

O’Connell, Thomas F.; Bradley, Christopher J.; Abbas, Amr E.; Williamson, Brian D.; Rusia, Akash; Tawney, Adam M.; Gaines, Rick; Schott, Jason; Dmitrienko, Alex; Haines, David E.

ABSTRACT Background Hydroxychloroquine and azithromycin (HCQ/AZM) are being widely used to treat COVID-19 despite the known risk of QT interval prolongation and unknown risk of arrhythmogenesis in this population. Objective The study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized COVID-19 patients treated with combination HCQ/AZM. Methods A retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated prior to drug administration and for the first 5 days following initiation. The primary end point was the magnitude of QTc prolongation, and factors associated with QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality. Results Among 415 patients receiving concomitant HCQ/AZM, the mean QTc increased from 443±25 msec to a maximum of 473±40 msec (87 (21%) had a QTc ≥500 msec). Factors associated with QTc prolongation ≥500 msec were age (p < 0.001), body mass index <30 kg/m2 (p = 0.005), heart failure (p < 0.001), elevated creatinine (p = 0.005), and peak troponin (p < 0.001). The change in QTc was not associated with death over the short period of the study in a population where mortality was already high (hazard ratio, 0.998, p = 0.607). No primary high-grade ventricular arrhythmias were observed. Conclusions An increase in QTc was seen in hospitalized COVID-19 patients treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.