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

JACC Clin Electrophysiol. 2021 Jan;7(1):16-25. doi: 10.1016/j.jacep.2020.07.016. Epub 2020 Aug 5.

Abstract

Objectives: This study aimed to characterize corrected QT (QTc) prolongation in a cohort of hospitalized patients with coronavirus disease-2019 (COVID-19) who were treated with hydroxychloroquine and azithromycin (HCQ/AZM).

Background: HCQ/AZM is being widely used to treat COVID-19 despite the known risk of QT interval prolongation and the unknown risk of arrhythmogenesis in this population.

Methods: A retrospective cohort of COVID-19 hospitalized patients treated with HCQ/AZM was reviewed. The QTc interval was calculated before drug administration and for the first 5 days following initiation. The primary endpoint 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 who received concomitant HCQ/AZM, the mean QTc increased from 443 ± 25 ms to a maximum of 473 ± 40 ms (87 [21%] patients had a QTc ≥500 ms). Factors associated with QTc prolongation ≥500 ms 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 in which 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 patients with COVID-19 treated with HCQ/AZM. Several clinical factors were associated with greater QTc prolongation. Changes in QTc were not associated with increased risk of death.

Keywords: COVID-19; QT prolongation; azithromycin; hydroxychloroquine; torsades de pointes.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects*
  • Azithromycin / adverse effects*
  • Body Mass Index
  • COVID-19 / epidemiology
  • COVID-19 Drug Treatment*
  • Comorbidity
  • Creatinine / blood
  • Drug Therapy, Combination
  • Electrocardiography
  • Enzyme Inhibitors / adverse effects*
  • Female
  • Heart Failure / epidemiology
  • Hospitalization
  • Humans
  • Hydroxychloroquine / adverse effects*
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / epidemiology
  • Male
  • Middle Aged
  • Mortality
  • Proportional Hazards Models
  • Risk Factors
  • SARS-CoV-2
  • Troponin I / blood

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Troponin I
  • Hydroxychloroquine
  • Azithromycin
  • Creatinine