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. 2021 Feb 1:324:242-248.
doi: 10.1016/j.ijcard.2020.09.038. Epub 2020 Sep 19.

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

Andrea Bernardini  1 , Giuseppe Ciconte  1 , Gabriele Negro  1 , Roberto Rondine  1 , Valerio Mecarocci  1 , Tommaso Viva  2 , Francesca Santini  1 , Carlo de Innocentiis  1 , Luigi Giannelli  1 , Ewa Witkowska  1 , Emanuela Teresina Locati  1 , Serenella Castelvecchio  3 , Massimiliano M Marrocco-Trischitta  4 , Gabriele Vicedomini  1 , Lorenzo Menicanti  3 , Carlo Pappone  5
Affiliations

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

Andrea Bernardini et al. Int J Cardiol. .

Abstract

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.

Keywords: Age; Azithromycin; COVID-19; ECG; Hydroxychloroquine; QT interval.

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Conflict of interest statement

Declaration of Competing Interest None.

Figures

Fig. 1
Fig. 1
Box plot analysis showing differences in QTc interval among the groups (left panel). Group 3 patients had a longer QTc interval compared to the other groups. Right panel shows incremental utility analysis between age and drug therapy and the risk of prolonged QT.
Fig. 2
Fig. 2
Kaplan-Meier analysis demonstrating patients' survival according to the treatment strategy.
See this image and copyright information in PMC

References

    1. Huang C., Wang Y., Li X., Ren L., Zhao J., Hu Y., Zhang L., Fan G., Xu J., Gu X., Cheng Z., Yu T., Xia J., Wei Y., Wu W., Xie X., Yin W., Li H., Liu M., Xiao Y., Gao H., Guo L., Xie J., Wang G., Jiang R., Gao Z., Jin Q., Wang J., Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497–506. doi: 10.1016/S0140-6736(20)30183-5. - DOI - PMC - PubMed
    1. WHO Director-General's Opening Remarks at the Media Briefing on COVID-19 - 11 March 2020. 2020. https://www.who.int/dg/speeches/detail/who-director-general-s-opening-re...
    1. Shi Y., Yu X., Zhao H., Wang H., Zhao R., Sheng J. Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan. Crit. Care. 2020;24:108. doi: 10.1186/s13054-020-2833-7. - DOI - PMC - PubMed
    1. Zheng Y.-Y., Ma Y.-T., Zhang J.-Y., Xie X. COVID-19 and the cardiovascular system. Nat. Rev. Cardiol. 2020;17:259–260. doi: 10.1038/s41569-020-0360-5. - DOI - PMC - PubMed
    1. Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323:1239–1242. doi: 10.1001/jama.2020.2648. - DOI - PubMed

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