tetano
Editor, Senior Moderator
Pharmacoepidemiol Drug Saf
. 2021 Mar 26.
doi: 10.1002/pds.5234. Online ahead of print.
QTc prolongation in COVID-19 patients treated with Hydroxychloroquine, Chloroquine, Azithromycin, or Lopinavir/Ritonavir: A systematic review and meta-analysis
Carlos Diaz-Arocutipa[SUP] 1 2 3 [/SUP], Ana Bra?ez-Condorena[SUP] 3 4 [/SUP], Adrian V Hernandez[SUP] 1 5 [/SUP]
Affiliations
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 ?500ms, peak QTc change ?60ms, 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) involving 13087 patients were included. The pooled prevalence of peak QTc ?500ms was 9% (95%CI [95% confidence interval], 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.
Keywords: COVID-19; QTc interval; Torsades de Pointes; sudden cardiac death; ventricular arrhythmias.
. 2021 Mar 26.
doi: 10.1002/pds.5234. Online ahead of print.
QTc prolongation in COVID-19 patients treated with Hydroxychloroquine, Chloroquine, Azithromycin, or Lopinavir/Ritonavir: A systematic review and meta-analysis
Carlos Diaz-Arocutipa[SUP] 1 2 3 [/SUP], Ana Bra?ez-Condorena[SUP] 3 4 [/SUP], Adrian V Hernandez[SUP] 1 5 [/SUP]
Affiliations
- PMID: 33772933
- DOI: 10.1002/pds.5234
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 ?500ms, peak QTc change ?60ms, 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) involving 13087 patients were included. The pooled prevalence of peak QTc ?500ms was 9% (95%CI [95% confidence interval], 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.
Keywords: COVID-19; QTc interval; Torsades de Pointes; sudden cardiac death; ventricular arrhythmias.