Hydroxychloroquine/Azithromycin and QT Prolongation in COVID-19

Quick Takes

  • Mean QTc of patients on hydroxychloroquine and azithromycin therapy increased from 443 to 473 ms and 21% of patients had a QTc ≥500 ms.
  • Factors associated with QTc prolongation were age, body mass index <30 kg/m2, heart failure, elevated creatinine, and peak troponin.
  • No primary high-grade ventricular arrhythmias or increased mortality were observed.

Study Questions:

What is the corrected QT (QTc) prolongation in a cohort of hospitalized coronavirus disease 2019 (COVID-19) patients treated with combination hydroxychloroquine and azithromycin (HCQ/AZM)?

Methods:

The authors assessed QTc in hospitalized patients at baseline and at 5 days of HCQ/AZM therapy. The primary endpoint was the magnitude of QTc prolongation. Secondary endpoints were incidences of sustained ventricular tachycardia or ventricular fibrillation and all-cause mortality.

Results:

There were 415 patients on HCQ/AZM. Mean QTc increased from 443 to 473 ms; 87 patients (21%) had a QTc ≥500 ms. Factors associated with QTc prolongation were age, body mass index <30 kg/m2, heart failure, elevated creatinine, and peak troponin. QTc increase was not associated with death in a population where mortality was already high. No primary high-grade ventricular arrhythmias were observed.

Conclusions:

An increase in QTc was seen in hospitalized COVID-19 patients treated with HCQ/AZM. Changes in QTc were not associated with increased risk of death.

Perspective:

Both chloroquine and HCQ may inhibit severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in vitro and their use was explored for the treatment of COVID-19. The current study shows that the average QTc prolongation with the coadministration of both agents is about 30 ms and that none of the patients sustained arrhythmogenic death. Subsequent controlled trials failed to show a clinical benefit for patients with COVID-19. This suggests that the actual risk of torsade de pointes in this setting is very low, or that the prescribing physicians were appropriately adjusting therapies in patients in whom excess QT prolongation was observed.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, Novel Agents, Statins, Acute Heart Failure

Keywords: Arrhythmias, Cardiac, Azithromycin, Body Mass Index, Chloroquine, Coronavirus, COVID-19, Creatinine, Heart Failure, Hydroxychloroquine, Long QT Syndrome, Primary Prevention, severe acute respiratory syndrome coronavirus 2, Tachycardia, Ventricular, Troponin, Ventricular Fibrillation


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