Title
QTc prolongation in COVID-19 patients treated with hydroxychloroquine, chloroquine, azithromycin, or lopinavir/ritonavir: A systematic review and meta-analysis
Date Issued
01 June 2021
Access level
open access
Resource Type
review
Author(s)
Publisher(s)
John Wiley and Sons Ltd
Abstract
Purpose: Hydroxychloroquine, chloroquine, azithromycin, and lopinavir/ritonavir are drugs that were used for the treatment of coronavirus disease 2019 (COVID-19) during the early pandemic period. It is well-known that these agents can prolong the QTc interval and potentially induce Torsades de Pointes (TdP). We aim to assess the prevalence and risk of QTc prolongation and arrhythmic events in COVID-19 patients treated with these drugs. Methods: We searched electronic databases from inception to September 30, 2020 for studies reporting peak QTc ≥500 ms, peak QTc change ≥60 ms, peak QTc interval, peak change of QTc interval, ventricular arrhythmias, TdP, sudden cardiac death, or atrioventricular block (AVB). All meta-analyses were conducted using a random-effects model. Results: Forty-seven studies (three case series, 35 cohorts, and nine randomized controlled trials [RCTs]) involving 13 087 patients were included. The pooled prevalence of peak QTc ≥500 ms was 9% (95% confidence interval [95%CI], 3%–18%) and 8% (95%CI, 3%–14%) in patients who received hydroxychloroquine/chloroquine alone or in combination with azithromycin, respectively. Likewise, the use of hydroxychloroquine (risk ratio [RR], 2.68; 95%CI, 1.56–4.60) and hydroxychloroquine + azithromycin (RR, 3.28; 95%CI, 1.16–9.30) was associated with an increased risk of QTc prolongation compared to no treatment. Ventricular arrhythmias, TdP, sudden cardiac death, and AVB were reported in <1% of patients across treatment groups. The only two studies that reported individual data of lopinavir/ritonavir found no cases of QTc prolongation. Conclusions: COVID-19 patients treated with hydroxychloroquine/chloroquine with or without azithromycin had a relatively high prevalence and risk of QTc prolongation. However, the prevalence of arrhythmic events was very low, probably due to underreporting. The limited information about lopinavir/ritonavir showed that it does not prolong the QTc interval.
Start page
694
End page
706
Volume
30
Issue
6
Language
English
OCDE Knowledge area
Farmacología, Farmacia
Sistema cardiaco, Sistema cardiovascular
Subjects
DOI
Scopus EID
2-s2.0-85103564874
PubMed ID
Source
Pharmacoepidemiology and Drug Safety
ISSN of the container
10538569
Sources of information:
Directorio de Producción Científica
Scopus