Effects on QT interval of hydroxychloroquine associated with ritonavir/darunavir or azithromycin in patients with SARS-CoV-2 infection.
Identifieur interne : 001118 ( Main/Corpus ); précédent : 001117; suivant : 001119Effects on QT interval of hydroxychloroquine associated with ritonavir/darunavir or azithromycin in patients with SARS-CoV-2 infection.
Auteurs : Luigi Moschini ; Marco Loffi ; Valentina Regazzoni ; Giuseppe Di Tano ; Elisa Gherbesi ; Gian Battista DanziSource :
- Heart and vessels [ 1615-2573 ] ; 2021.
English descriptors
- KwdEn :
- Aged (MeSH), Anti-Bacterial Agents (adverse effects), Anti-Bacterial Agents (therapeutic use), Azithromycin (adverse effects), Azithromycin (therapeutic use), COVID-19 (drug therapy), COVID-19 (epidemiology), Darunavir (adverse effects), Darunavir (therapeutic use), Electrocardiography (drug effects), Enzyme Inhibitors (therapeutic use), Female (MeSH), Humans (MeSH), Hydroxychloroquine (therapeutic use), Long QT Syndrome (chemically induced), Long QT Syndrome (physiopathology), Male (MeSH), Middle Aged (MeSH), Ritonavir (adverse effects), Ritonavir (therapeutic use), SARS-CoV-2 (MeSH).
- MESH :
- chemical , adverse effects : Anti-Bacterial Agents, Azithromycin, Darunavir, Ritonavir.
- chemical , therapeutic use : Anti-Bacterial Agents, Azithromycin, Darunavir, Enzyme Inhibitors, Hydroxychloroquine, Ritonavir.
- chemically induced : Long QT Syndrome.
- drug effects : Electrocardiography.
- drug therapy : COVID-19.
- epidemiology : COVID-19.
- physiopathology : Long QT Syndrome.
- Aged, Female, Humans, Male, Middle Aged, SARS-CoV-2.
Abstract
INTRODUCTION
Most of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc).
OBJECTIVE
To evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals.
METHODS
At the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ. Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy. We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group).
RESULTS
A significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days. The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001). One patient per group suffered a malignant ventricular arrhythmia.
CONCLUSION
Hydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days. The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time.
DOI: 10.1007/s00380-020-01671-4
PubMed: 32676695
PubMed Central: PMC7364290
Links to Exploration step
pubmed:32676695Le document en format XML
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Cremona, Viale Concordia 1, 26100, Cremona, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Di Tano, Giuseppe" sort="Di Tano, Giuseppe" uniqKey="Di Tano G" first="Giuseppe" last="Di Tano">Giuseppe Di Tano</name><affiliation><nlm:affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Gherbesi, Elisa" sort="Gherbesi, Elisa" uniqKey="Gherbesi E" first="Elisa" last="Gherbesi">Elisa Gherbesi</name><affiliation><nlm:affiliation>Università degli Studi di Milano, Via Festa del Perdono 7, 20122, Milano, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Danzi, Gian Battista" sort="Danzi, Gian Battista" uniqKey="Danzi G" first="Gian Battista" last="Danzi">Gian Battista Danzi</name><affiliation><nlm:affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy. 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sortKey="Loffi, Marco" sort="Loffi, Marco" uniqKey="Loffi M" first="Marco" last="Loffi">Marco Loffi</name><affiliation><nlm:affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Regazzoni, Valentina" sort="Regazzoni, Valentina" uniqKey="Regazzoni V" first="Valentina" last="Regazzoni">Valentina Regazzoni</name><affiliation><nlm:affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Di Tano, Giuseppe" sort="Di Tano, Giuseppe" uniqKey="Di Tano G" first="Giuseppe" last="Di Tano">Giuseppe Di Tano</name><affiliation><nlm:affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Gherbesi, Elisa" sort="Gherbesi, Elisa" uniqKey="Gherbesi E" first="Elisa" last="Gherbesi">Elisa Gherbesi</name><affiliation><nlm:affiliation>Università degli Studi di Milano, Via Festa del Perdono 7, 20122, Milano, Italy.</nlm:affiliation></affiliation></author><author><name sortKey="Danzi, Gian Battista" sort="Danzi, Gian Battista" uniqKey="Danzi G" first="Gian Battista" last="Danzi">Gian Battista Danzi</name><affiliation><nlm:affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy. gbdanzi@gmail.com.</nlm:affiliation></affiliation></author></analytic><series><title level="j">Heart and vessels</title><idno type="eISSN">1615-2573</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged (MeSH)</term><term>Anti-Bacterial Agents (adverse effects)</term><term>Anti-Bacterial Agents (therapeutic use)</term><term>Azithromycin (adverse effects)</term><term>Azithromycin (therapeutic use)</term><term>COVID-19 (drug therapy)</term><term>COVID-19 (epidemiology)</term><term>Darunavir (adverse effects)</term><term>Darunavir (therapeutic use)</term><term>Electrocardiography (drug effects)</term><term>Enzyme Inhibitors (therapeutic use)</term><term>Female (MeSH)</term><term>Humans (MeSH)</term><term>Hydroxychloroquine (therapeutic use)</term><term>Long QT Syndrome (chemically induced)</term><term>Long QT Syndrome (physiopathology)</term><term>Male (MeSH)</term><term>Middle Aged (MeSH)</term><term>Ritonavir (adverse effects)</term><term>Ritonavir (therapeutic use)</term><term>SARS-CoV-2 (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Azithromycin</term><term>Darunavir</term><term>Ritonavir</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Anti-Bacterial Agents</term><term>Azithromycin</term><term>Darunavir</term><term>Enzyme Inhibitors</term><term>Hydroxychloroquine</term><term>Ritonavir</term></keywords><keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Long QT Syndrome</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Electrocardiography</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="epidemiology" xml:lang="en"><term>COVID-19</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Long QT Syndrome</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>SARS-CoV-2</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><b>INTRODUCTION</b></p><p>Most of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc).</p></div><div type="abstract" xml:lang="en"><p><b>OBJECTIVE</b></p><p>To evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals.</p></div><div type="abstract" xml:lang="en"><p><b>METHODS</b></p><p>At the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ. Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy. We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group).</p></div><div type="abstract" xml:lang="en"><p><b>RESULTS</b></p><p>A significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days. The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001). One patient per group suffered a malignant ventricular arrhythmia.</p></div><div type="abstract" xml:lang="en"><p><b>CONCLUSION</b></p><p>Hydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days. The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time.</p></div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32676695</PMID><DateCompleted><Year>2021</Year><Month>01</Month><Day>13</Day></DateCompleted><DateRevised><Year>2021</Year><Month>01</Month><Day>13</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1615-2573</ISSN><JournalIssue CitedMedium="Internet"><Volume>36</Volume><Issue>1</Issue><PubDate><Year>2021</Year><Month>Jan</Month></PubDate></JournalIssue><Title>Heart and vessels</Title><ISOAbbreviation>Heart Vessels</ISOAbbreviation></Journal><ArticleTitle>Effects on QT interval of hydroxychloroquine associated with ritonavir/darunavir or azithromycin in patients with SARS-CoV-2 infection.</ArticleTitle><Pagination><MedlinePgn>115-120</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1007/s00380-020-01671-4</ELocationID><Abstract><AbstractText Label="INTRODUCTION" NlmCategory="BACKGROUND">Most of the drugs associations that have been used to treat patients with SARS-CoV-2 infection increase the risk of prolongation of the corrected QT interval (QTc).</AbstractText><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">To evaluate the effects of an association therapy of hydroxychloroquine (HY) plus ritonavir/darunavir (RD) or azithromycin (AZ) on QTc intervals.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">At the beginning of COVID-19 pandemic patients admitted to our hospital were treated with the empiric association of HY/RD; one week later the therapeutic protocol was modified with the combination of HY/AZ. Patients underwent an ECG at baseline, then 3 and 7 days after starting therapy. We prospectively enrolled 113 patients (61 in the HY/RD group-52 in the HY/AZ group).</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">A significant increase in median QTc was reported after seven days of therapy in both groups: from 438 to 452 ms in HY/RD patients; from 433 to 440 ms in HY/AZ patients (p = 0.001 for both). 23 patients (21.2%) had a QTc > 500 ms at 7 days. The risk of developing a QTc > 500 ms was greater in patients with prolonged baseline QTc values (≥ 440 ms for female and ≥ 460 ms for male patients) (OR 7.10 (95% IC 1.88-26.81); p = 0.004) and in patients with an increase in the QTc > 40 ms 3 days after onset of treatment (OR 30.15 (95% IC 6.96-130.55); p = 0.001). One patient per group suffered a malignant ventricular arrhythmia.</AbstractText><AbstractText Label="CONCLUSION" NlmCategory="CONCLUSIONS">Hydroxychloroquine with both ritonavir/darunavir or azithromycin therapy significantly increased the QTc-interval at 7 days. The risk of developing malignant arrhythmias remained relatively low when these drugs were administered for a limited period of time.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Moschini</LastName><ForeName>Luigi</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Loffi</LastName><ForeName>Marco</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Regazzoni</LastName><ForeName>Valentina</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Di Tano</LastName><ForeName>Giuseppe</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gherbesi</LastName><ForeName>Elisa</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Università degli Studi di Milano, Via Festa del Perdono 7, 20122, Milano, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Danzi</LastName><ForeName>Gian Battista</ForeName><Initials>GB</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-0897-8006</Identifier><AffiliationInfo><Affiliation>Division of Cardiology, Ospedale di Cremona, Viale Concordia 1, 26100, Cremona, Italy. gbdanzi@gmail.com.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>07</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>Japan</Country><MedlineTA>Heart Vessels</MedlineTA><NlmUniqueID>8511258</NlmUniqueID><ISSNLinking>0910-8327</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D000900">Anti-Bacterial Agents</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D004791">Enzyme Inhibitors</NameOfSubstance></Chemical><Chemical><RegistryNumber>4QWG6N8QKH</RegistryNumber><NameOfSubstance UI="D006886">Hydroxychloroquine</NameOfSubstance></Chemical><Chemical><RegistryNumber>83905-01-5</RegistryNumber><NameOfSubstance UI="D017963">Azithromycin</NameOfSubstance></Chemical><Chemical><RegistryNumber>O3J8G9O825</RegistryNumber><NameOfSubstance UI="D019438">Ritonavir</NameOfSubstance></Chemical><Chemical><RegistryNumber>YO603Y8113</RegistryNumber><NameOfSubstance UI="D000069454">Darunavir</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000900" MajorTopicYN="N">Anti-Bacterial Agents</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="N">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017963" MajorTopicYN="N">Azithromycin</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086382" MajorTopicYN="N">COVID-19</DescriptorName><QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName><QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000069454" MajorTopicYN="N">Darunavir</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName><QualifierName UI="Q000187" MajorTopicYN="Y">drug effects</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004791" MajorTopicYN="N">Enzyme Inhibitors</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D006886" MajorTopicYN="N">Hydroxychloroquine</DescriptorName><QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008133" MajorTopicYN="N">Long QT Syndrome</DescriptorName><QualifierName UI="Q000139" MajorTopicYN="Y">chemically induced</QualifierName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D019438" MajorTopicYN="N">Ritonavir</DescriptorName><QualifierName UI="Q000009" MajorTopicYN="Y">adverse effects</QualifierName><QualifierName UI="Q000627" MajorTopicYN="N">therapeutic use</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D000086402" MajorTopicYN="N">SARS-CoV-2</DescriptorName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Azithromycin</Keyword><Keyword 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