Assessing QT interval in COVID-19 patients:safety of hydroxychloroquine-azithromycin combination regimen

Andrea Bernardini, Giuseppe Ciconte, Gabriele Negro, Roberto Rondine, Valerio Mecarocci, Tommaso Viva, Francesca Santini, Carlo de Innocentiis, Luigi Giannelli, Ewa Witkowska, Emanuela Teresina Locati, Serenella Castelvecchio, Massimiliano M Marrocco-Trischitta, Gabriele Vicedomini, Lorenzo Menicanti, Carlo Pappone

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Hydroxychloroquine (HCQ) and azithromycin (AZT) have been proposed for COVID-19 treatment. Data available in the literature reported a potential increased risk of fatal arrhythmias under these therapies. The aim of this study was to assess the effects of these drugs on QT interval and outcome in a COVID-19 population.

METHOD: A total of 112 consecutive COVID-19 patients were included in this analysis and were divided in 3 groups according to the receiving therapeutic regimens: 19 (17%) patients in Group 1 (no treatment), 40 (36%) in Group 2 (HCQ only), 53 (47%) in Group 3 (HCQ/AZT).

RESULTS: A prolonged QTc interval was found in 61% of patients treated with HCQ alone or in combination with AZT, but only 4 (4%) patients showed a QTc > 500 ms. HCQ/AZT combination determined a greater increase of QTc duration compared to the other two strategies (Group 3 452 ± 26.4 vs Group 2 436.3 ± 28.4 vs Group 1 424.4 ± 24.3 ms, respectively; p < 0.001). Multivariate analysis demonstrated that HCQ/AZT combination (OR 9.02, p = 0.001) and older age (OR 1.04, p = 0.031) were independent predictors of QTc prolongation. The risk increased with age (incremental utility analysis p = 0.02). Twenty patients (18%) died, and no cardiac arrest neither arrhythmic fatalities were documented.

CONCLUSIONS: The HCQ/AZT combination therapy causes a significantly increase of QT interval compared to HCQ alone. Older patients under such regimen are at higher risk of experiencing QT prolongation. The use of such drugs may be considered as safe relating to arrhythmic risk in the treatment of COVID-19 patients as no arrhythmic fatalities occurred.

Original languageEnglish
Pages (from-to)242-248
Number of pages7
JournalInternational Journal of Cardiology
Publication statusPublished - Feb 1 2021


  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents/administration & dosage
  • Antimalarials/administration & dosage
  • Azithromycin/administration & dosage
  • COVID-19/chemically induced
  • Drug Therapy, Combination
  • Electrocardiography/drug effects
  • Female
  • Follow-Up Studies
  • Humans
  • Hydroxychloroquine/administration & dosage
  • Long QT Syndrome/diagnosis
  • Male
  • Middle Aged
  • Patient Safety
  • Retrospective Studies

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