QTc prolongation in COVID-19 patients treated with hydroxychloroquine, chloroquine, azithromycin, or lopinavir/ritonavir: A systematic review and meta-analysis.
Identifieur interne : 000181 ( Main/Corpus ); précédent : 000180; suivant : 000182QTc prolongation in COVID-19 patients treated with hydroxychloroquine, chloroquine, azithromycin, or lopinavir/ritonavir: A systematic review and meta-analysis.
Auteurs : Carlos Diaz-Arocutipa ; Ana Bra Ez-Condorena ; Adrian V. HernandezSource :
- Pharmacoepidemiology and drug safety [ 1099-1557 ] ; 2021.
English descriptors
- KwdEn :
- Azithromycin (administration & dosage), Azithromycin (adverse effects), COVID-19 (diagnosis), COVID-19 (drug therapy), COVID-19 (epidemiology), Chloroquine (administration & dosage), Chloroquine (adverse effects), Humans (MeSH), Hydroxychloroquine (administration & dosage), Hydroxychloroquine (adverse effects), Long QT Syndrome (chemically induced), Long QT Syndrome (diagnosis), Long QT Syndrome (epidemiology), Lopinavir (administration & dosage), Lopinavir (adverse effects), Observational Studies as Topic (methods), Ritonavir (administration & dosage), Ritonavir (adverse effects).
- MESH :
- chemical , administration & dosage : Azithromycin, Chloroquine, Hydroxychloroquine, Lopinavir, Ritonavir.
- chemical , adverse effects : Azithromycin, Chloroquine, Hydroxychloroquine, Lopinavir, Ritonavir.
- chemically induced : Long QT Syndrome.
- diagnosis : COVID-19, Long QT Syndrome.
- drug therapy : COVID-19.
- epidemiology : COVID-19, Long QT Syndrome.
- methods : Observational Studies as Topic.
- Humans.
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.
DOI: 10.1002/pds.5234
PubMed: 33772933
Links to Exploration step
pubmed:33772933Le document en format XML
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<author><name sortKey="Diaz Arocutipa, Carlos" sort="Diaz Arocutipa, Carlos" uniqKey="Diaz Arocutipa C" first="Carlos" last="Diaz-Arocutipa">Carlos Diaz-Arocutipa</name>
<affiliation><nlm:affiliation>Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Peru.</nlm:affiliation>
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<affiliation><nlm:affiliation>Programa de Atención Domiciliaria - EsSalud, Lima, Peru.</nlm:affiliation>
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<affiliation><nlm:affiliation>Asociación para el Desarrollo de la Investigación Estudiantil en Ciencias de la Salud (ADIECS), Lima, Peru.</nlm:affiliation>
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<author><name sortKey="Bra Ez Condorena, Ana" sort="Bra Ez Condorena, Ana" uniqKey="Bra Ez Condorena A" first="Ana" last="Bra Ez-Condorena">Ana Bra Ez-Condorena</name>
<affiliation><nlm:affiliation>Asociación para el Desarrollo de la Investigación Estudiantil en Ciencias de la Salud (ADIECS), Lima, Peru.</nlm:affiliation>
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<affiliation><nlm:affiliation>Facultad de Medicina de San Fernando, Universidad Nacional Mayor de San Marcos, Lima, Peru.</nlm:affiliation>
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<author><name sortKey="Hernandez, Adrian V" sort="Hernandez, Adrian V" uniqKey="Hernandez A" first="Adrian V" last="Hernandez">Adrian V. Hernandez</name>
<affiliation><nlm:affiliation>Vicerrectorado de Investigación, Universidad San Ignacio de Loyola, Lima, Peru.</nlm:affiliation>
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<affiliation><nlm:affiliation>Health Outcomes, Policy, and Evidence Synthesis (HOPES) Group, University of Connecticut School of Pharmacy, Storrs, Connecticut, USA.</nlm:affiliation>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">QTc prolongation in COVID-19 patients treated with hydroxychloroquine, chloroquine, azithromycin, or lopinavir/ritonavir: A systematic review and meta-analysis.</title>
<author><name sortKey="Diaz Arocutipa, Carlos" sort="Diaz Arocutipa, Carlos" uniqKey="Diaz Arocutipa C" first="Carlos" last="Diaz-Arocutipa">Carlos Diaz-Arocutipa</name>
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<affiliation><nlm:affiliation>Programa de Atención Domiciliaria - EsSalud, Lima, Peru.</nlm:affiliation>
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<affiliation><nlm:affiliation>Asociación para el Desarrollo de la Investigación Estudiantil en Ciencias de la Salud (ADIECS), Lima, Peru.</nlm:affiliation>
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<author><name sortKey="Bra Ez Condorena, Ana" sort="Bra Ez Condorena, Ana" uniqKey="Bra Ez Condorena A" first="Ana" last="Bra Ez-Condorena">Ana Bra Ez-Condorena</name>
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<author><name sortKey="Hernandez, Adrian V" sort="Hernandez, Adrian V" uniqKey="Hernandez A" first="Adrian V" last="Hernandez">Adrian V. Hernandez</name>
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<term>Azithromycin (adverse effects)</term>
<term>COVID-19 (diagnosis)</term>
<term>COVID-19 (drug therapy)</term>
<term>COVID-19 (epidemiology)</term>
<term>Chloroquine (administration & dosage)</term>
<term>Chloroquine (adverse effects)</term>
<term>Humans (MeSH)</term>
<term>Hydroxychloroquine (administration & dosage)</term>
<term>Hydroxychloroquine (adverse effects)</term>
<term>Long QT Syndrome (chemically induced)</term>
<term>Long QT Syndrome (diagnosis)</term>
<term>Long QT Syndrome (epidemiology)</term>
<term>Lopinavir (administration & dosage)</term>
<term>Lopinavir (adverse effects)</term>
<term>Observational Studies as Topic (methods)</term>
<term>Ritonavir (administration & dosage)</term>
<term>Ritonavir (adverse effects)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Azithromycin</term>
<term>Chloroquine</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Azithromycin</term>
<term>Chloroquine</term>
<term>Hydroxychloroquine</term>
<term>Lopinavir</term>
<term>Ritonavir</term>
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<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Long QT Syndrome</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>COVID-19</term>
<term>Long QT Syndrome</term>
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<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term>
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<term>Long QT Syndrome</term>
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<front><div type="abstract" xml:lang="en"><p><b>PURPOSE</b>
</p>
<p>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.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>METHODS</b>
</p>
<p>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.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>RESULTS</b>
</p>
<p>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.</p>
</div>
<div type="abstract" xml:lang="en"><p><b>CONCLUSIONS</b>
</p>
<p>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.</p>
</div>
</front>
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<Abstract><AbstractText Label="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.</AbstractText>
<AbstractText Label="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.</AbstractText>
<AbstractText Label="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.</AbstractText>
<AbstractText Label="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.</AbstractText>
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<AffiliationInfo><Affiliation>Programa de Atención Domiciliaria - EsSalud, Lima, Peru.</Affiliation>
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<AffiliationInfo><Affiliation>Facultad de Medicina de San Fernando, Universidad Nacional Mayor de San Marcos, Lima, Peru.</Affiliation>
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