Experience with Hydroxychloroquine and Azithromycin in the COVID-19 Pandemic: Implications for QT Interval Monitoring

Authors:
  • ARArchana Ramireddy
    Archana Ramireddy
  • HCHarpriya Chugh
    Harpriya Chugh
  • KRKyndaron Reinier
    Kyndaron Reinier
  • JEJoseph Ebinger
    Joseph Ebinger
  • EPEunice Park
    Eunice Park
  • MTMichael Thompson
    Michael Thompson
  • ECEugenio Cingolani
    Eugenio Cingolani
  • SCSusan Cheng
    Susan Cheng
  • EMEduardo Marban
    Eduardo Marban
  • CAChristine M. Albert
    Christine M. Albert
  • SCSumeet S. Chugh
    Sumeet S. Chugh
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Abstract
Background: Despite a paucity of clinical evidence, hydroxychloroquine and azithromycin are being administered widely to patients with verified or suspected COVID-19. Both drugs may increase risk of lethal arrhythmias associated with QT interval prolongation. Methods: We performed a case series of COVID-19 positive/suspected patients admitted between 2/1/2020 and 4/4/2020 who were treated with azithromycin, hydroxychloroquine or a combination. We evaluated baseline and post-medication QT interval (QTc, Bazett’s) using 12-lead ECGs. Critical QTc prolongation was defined as: a) maximum QTc ≥500 ms (if QRS 0.14). Changes in QTc were highest with the combination compared to either drug, with many-fold greater prolongation with the combination vs. azithromycin alone (17±39 vs. 0.5±40 ms, p=0.07). No patients manifested torsades de pointes. Conclusions: Overall, 12% of patients manifested critical QTc interval prolongation, and traditional risk indices failed to flag these patients. With the drug combination, QTc prolongation was several-fold higher compared to azithromycin alone. The balance between uncertain benefit and potential risk when treating COVID-19 patients with these drugs should be carefully assessed prior to use.
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