QT prolongation in a diverse, urban population of COVID-19 patients treated with hydroxychloroquine, chloroquine, or azithromycin

J Interv Card Electrophysiol. 2020 Nov;59(2):337-345. doi: 10.1007/s10840-020-00822-x. Epub 2020 Jul 11.

Abstract

Purpose: Hydroxychloroquine, chloroquine, and azithromycin have been used for treatment of COVID-19, but may cause QT prolongation. Minority populations are disproportionately impacted by COVID-19. This study evaluates the risk of QT prolongation and subsequent outcomes after administration of these medications in largely underrepresented minority COVID-19 patients.

Methods: We conducted an observational study on hospitalized COVID-19 patients in the Montefiore Health System (Bronx, NY). We examined electrocardiograms (ECG) pre/post-medication initiation to evaluate QTc, HR, QRS duration, and presence of other arrhythmias.

Results: One hundred five patients (mean age 67 years; 44.8% F) were analyzed. The median time from the first dose of any treatment to post-medication ECG was 2 days (IQR: 1-3). QTc in men increased from baseline (440 vs 455 ms, p < 0.001), as well as in women (438 vs 463 ms, p < 0.001). The proportion of patients with QT prolongation increased significantly (14.3% vs 34.3%, p < 0.001) even when adjusted for electrolyte abnormalities. The number of patients whose QTc > 500 ms was significantly increased after treatment (16.2% vs. 4.8%, p < 0.01). Patients with either QTc > 500 ms or an increase of 60 ms had a higher frequency of death (47.6% vs. 22.6%, p = 0.02) with an odds ratio of 3.1 (95% CI: 1.1-8.7). Adjusting for race/ethnicity yielded no significant associations.

Conclusions: Hydroxychloroquine, chloroquine, and/or azithromycin were associated with QTc prolongation but did not result in fatal arrhythmias. Our findings suggest that any harm is unlikely to outweigh potential benefits of treatment. Careful risk-benefit analyses for individual patients should guide the use of these medications. Randomized control trials are necessary to evaluate their efficacies.

Keywords: Azithromycin; COVID-19; Chloroquine; Hydroxychloroquine; QT; SARS-CoV-2.

Publication types

  • Observational Study

MeSH terms

  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Antimalarials / administration & dosage
  • Antimalarials / adverse effects*
  • Azithromycin / administration & dosage
  • Azithromycin / adverse effects*
  • COVID-19
  • Chloroquine / administration & dosage
  • Chloroquine / adverse effects
  • Coronavirus Infections / diagnosis
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / epidemiology
  • Electrocardiography / methods*
  • Female
  • Follow-Up Studies
  • Hospitalization / statistics & numerical data
  • Humans
  • Hydroxychloroquine / administration & dosage
  • Hydroxychloroquine / adverse effects
  • Incidence
  • Long QT Syndrome / chemically induced*
  • Long QT Syndrome / diagnostic imaging
  • Long QT Syndrome / drug therapy
  • Long QT Syndrome / epidemiology
  • Male
  • Middle Aged
  • Pandemics / prevention & control
  • Pandemics / statistics & numerical data
  • Pneumonia, Viral / diagnosis
  • Pneumonia, Viral / drug therapy*
  • Pneumonia, Viral / epidemiology
  • Risk Assessment
  • Sex Distribution
  • Urban Population

Substances

  • Antimalarials
  • Hydroxychloroquine
  • Azithromycin
  • Chloroquine