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Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people.

Identifieur interne : 000259 ( Main/Exploration ); précédent : 000258; suivant : 000260

Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people.

Auteurs : Julia Hippisley-Cox [Royaume-Uni] ; Duncan Young [Royaume-Uni] ; Carol Coupland [Royaume-Uni] ; Keith M. Channon [Royaume-Uni] ; Pui San Tan [Royaume-Uni] ; David A. Harrison [Royaume-Uni] ; Kathryn Rowan [Royaume-Uni] ; Paul Aveyard [Royaume-Uni] ; Ian D. Pavord [Royaume-Uni] ; Peter J. Watkinson [Royaume-Uni]

Source :

RBID : pubmed:32737124

Descripteurs français

English descriptors

Abstract

BACKGROUND

There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.

METHODS

This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20-99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.

FINDINGS

Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.

INTERPRETATION

ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.


DOI: 10.1136/heartjnl-2020-317393
PubMed: 32737124
PubMed Central: PMC7509391


Affiliations:

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<term>Angiotensin-Converting Enzyme Inhibitors (therapeutic use)</term>
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<term>Critical Care (statistics & numerical data)</term>
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<term>Adulte (MeSH)</term>
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<term>Infections à coronavirus (épidémiologie)</term>
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<term>Jeune adulte (MeSH)</term>
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<term>Angleterre</term>
<term>Infections à coronavirus</term>
<term>Pneumopathie virale</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Adult</term>
<term>Aged</term>
<term>Aged, 80 and over</term>
<term>Betacoronavirus</term>
<term>Cohort Studies</term>
<term>Health Status</term>
<term>Humans</term>
<term>Middle Aged</term>
<term>Pandemics</term>
<term>Risk Factors</term>
<term>Socioeconomic Factors</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Betacoronavirus</term>
<term>Facteurs de risque</term>
<term>Facteurs socioéconomiques</term>
<term>Humains</term>
<term>Jeune adulte</term>
<term>Pandémies</term>
<term>Sujet âgé</term>
<term>Sujet âgé de 80 ans ou plus</term>
<term>État de santé</term>
<term>Études de cohortes</term>
</keywords>
</textClass>
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<front>
<div type="abstract" xml:lang="en">
<p>
<b>BACKGROUND</b>
</p>
<p>There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>METHODS</b>
</p>
<p>This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20-99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>FINDINGS</b>
</p>
<p>Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.</p>
</div>
<div type="abstract" xml:lang="en">
<p>
<b>INTERPRETATION</b>
</p>
<p>ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.</p>
</div>
</front>
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<DateCompleted>
<Year>2020</Year>
<Month>09</Month>
<Day>23</Day>
</DateCompleted>
<DateRevised>
<Year>2020</Year>
<Month>10</Month>
<Day>07</Day>
</DateRevised>
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<Journal>
<ISSN IssnType="Electronic">1468-201X</ISSN>
<JournalIssue CitedMedium="Internet">
<Volume>106</Volume>
<Issue>19</Issue>
<PubDate>
<Year>2020</Year>
<Month>10</Month>
</PubDate>
</JournalIssue>
<Title>Heart (British Cardiac Society)</Title>
<ISOAbbreviation>Heart</ISOAbbreviation>
</Journal>
<ArticleTitle>Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people.</ArticleTitle>
<Pagination>
<MedlinePgn>1503-1511</MedlinePgn>
</Pagination>
<ELocationID EIdType="doi" ValidYN="Y">10.1136/heartjnl-2020-317393</ELocationID>
<Abstract>
<AbstractText Label="BACKGROUND">There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.</AbstractText>
<AbstractText Label="METHODS">This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20-99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.</AbstractText>
<AbstractText Label="FINDINGS">Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.</AbstractText>
<AbstractText Label="INTERPRETATION">ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.</AbstractText>
<CopyrightInformation>© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.</CopyrightInformation>
</Abstract>
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<Author ValidYN="Y">
<LastName>Hippisley-Cox</LastName>
<ForeName>Julia</ForeName>
<Initials>J</Initials>
<Identifier Source="ORCID">0000-0002-2479-7283</Identifier>
<AffiliationInfo>
<Affiliation>Primary Care Health Sciences, University of Oxford, Oxford, UK Julia.Hippisley-Cox@phc.ox.ac.uk.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Young</LastName>
<ForeName>Duncan</ForeName>
<Initials>D</Initials>
<AffiliationInfo>
<Affiliation>Adult Intensive Care Unit, John Radcliffe Hospital, Oxford, UK.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Kadoorie Centre, University of Oxford, Oxford, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Coupland</LastName>
<ForeName>Carol</ForeName>
<Initials>C</Initials>
<AffiliationInfo>
<Affiliation>Division of Primary Care, School of Medicine, University of Nottingham, Nottingham, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Channon</LastName>
<ForeName>Keith M</ForeName>
<Initials>KM</Initials>
<AffiliationInfo>
<Affiliation>Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, John Radcliffe Hospital, University of Oxford, Oxford, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Tan</LastName>
<ForeName>Pui San</ForeName>
<Initials>PS</Initials>
<AffiliationInfo>
<Affiliation>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.</Affiliation>
</AffiliationInfo>
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<LastName>Harrison</LastName>
<ForeName>David A</ForeName>
<Initials>DA</Initials>
<Identifier Source="ORCID">0000-0002-9002-9098</Identifier>
<AffiliationInfo>
<Affiliation>Clinical Trials Unit, ICNARC, London, UK.</Affiliation>
</AffiliationInfo>
</Author>
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<LastName>Rowan</LastName>
<ForeName>Kathryn</ForeName>
<Initials>K</Initials>
<AffiliationInfo>
<Affiliation>Intensive Care National Audit and Research Centre ICNARC, London, UK.</Affiliation>
</AffiliationInfo>
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<LastName>Aveyard</LastName>
<ForeName>Paul</ForeName>
<Initials>P</Initials>
<AffiliationInfo>
<Affiliation>Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Pavord</LastName>
<ForeName>Ian D</ForeName>
<Initials>ID</Initials>
<AffiliationInfo>
<Affiliation>Respiratory Medicine Unit and Oxford Respiratory NIHR BRC Nuffield Department of MedicineNDM Research BuildingOld Road CampusUniversity of Oxford, Oxford, UK.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y">
<LastName>Watkinson</LastName>
<ForeName>Peter J</ForeName>
<Initials>PJ</Initials>
<Identifier Source="ORCID">0000-0003-1023-3927</Identifier>
<AffiliationInfo>
<Affiliation>Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, John Radcliffe Hospital, University of Oxford, Oxford, UK.</Affiliation>
</AffiliationInfo>
<AffiliationInfo>
<Affiliation>Nuffield Department of Clinical Neurosciences, Oxford NIHR BRC, University of Oxford, Oxford, UK.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<GrantList CompleteYN="Y">
<Grant>
<Acronym>WT_</Acronym>
<Agency>Wellcome Trust</Agency>
<Country>United Kingdom</Country>
</Grant>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic">
<Year>2020</Year>
<Month>07</Month>
<Day>31</Day>
</ArticleDate>
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<MedlineJournalInfo>
<Country>England</Country>
<MedlineTA>Heart</MedlineTA>
<NlmUniqueID>9602087</NlmUniqueID>
<ISSNLinking>1355-6037</ISSNLinking>
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<ChemicalList>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D057911">Angiotensin Receptor Antagonists</NameOfSubstance>
</Chemical>
<Chemical>
<RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D000806">Angiotensin-Converting Enzyme Inhibitors</NameOfSubstance>
</Chemical>
</ChemicalList>
<SupplMeshList>
<SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName>
<SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName>
</SupplMeshList>
<CitationSubset>AIM</CitationSubset>
<CitationSubset>IM</CitationSubset>
<CommentsCorrectionsList>
<CommentsCorrections RefType="CommentIn">
<RefSource>Heart. 2020 Oct;106(19):1461-1462</RefSource>
<PMID Version="1">32759292</PMID>
</CommentsCorrections>
<CommentsCorrections RefType="CommentIn">
<RefSource>Heart. 2020 Oct;106(19):1451-1453</RefSource>
<PMID Version="1">32928982</PMID>
</CommentsCorrections>
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<MeshHeadingList>
<MeshHeading>
<DescriptorName UI="D000328" MajorTopicYN="N">Adult</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000368" MajorTopicYN="N">Aged</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D057911" MajorTopicYN="N">Angiotensin Receptor Antagonists</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000806" MajorTopicYN="N">Angiotensin-Converting Enzyme Inhibitors</DescriptorName>
<QualifierName UI="Q000627" MajorTopicYN="Y">therapeutic use</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D000073640" MajorTopicYN="Y">Betacoronavirus</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D015331" MajorTopicYN="N">Cohort Studies</DescriptorName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000175" MajorTopicYN="N">diagnosis</QualifierName>
<QualifierName UI="Q000453" MajorTopicYN="Y">epidemiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D003422" MajorTopicYN="N">Critical Care</DescriptorName>
<QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D004739" MajorTopicYN="N" Type="Geographic">England</DescriptorName>
<QualifierName UI="Q000453" MajorTopicYN="N">epidemiology</QualifierName>
</MeshHeading>
<MeshHeading>
<DescriptorName UI="D006304" MajorTopicYN="N">Health Status</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D006760" MajorTopicYN="N">Hospitalization</DescriptorName>
<QualifierName UI="Q000706" MajorTopicYN="N">statistics & numerical data</QualifierName>
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<MeshHeading>
<DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
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<DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
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<DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName>
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<MeshHeading>
<DescriptorName UI="D055815" MajorTopicYN="N">Young Adult</DescriptorName>
</MeshHeading>
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<Keyword MajorTopicYN="Y">cardiac risk factors and prevention</Keyword>
<Keyword MajorTopicYN="Y">diabetes</Keyword>
<Keyword MajorTopicYN="Y">epidemiology</Keyword>
<Keyword MajorTopicYN="Y">hypertension</Keyword>
<Keyword MajorTopicYN="Y">primary care</Keyword>
</KeywordList>
<CoiStatement>Competing interests: JHC reports grants from National Institute for Health Research Biomedical Research Centre, Oxford, grants from John Fell Oxford University Press Research Fund, grants from Cancer Research UK (CR-UK) grant number C5255/A18085, through the Cancer Research UK Oxford Centre, grants from the Oxford Wellcome Institutional Strategic Support Fund (204826/Z/16/Z), during the conduct of the study; personal fees and other from ClinRisk Ltd (until 2019) outside the submitted work; and JH is an unpaid director of QResearch, a not-for-profit organisation which is a partnership between the University of Oxford and EMIS Health who supply the QResearch database used for this work. PW reports grants from National Institute for Health Research Biomedical Research Centre, Oxford and the Wellcome Trust (grant number is 221514/Z/20/Z), during the conduct of the study; grants from Sensyne Health, personal fees from Sensyne Health, outside the submitted work. PST reports consulting with AstraZeneca and Duke-NUS outside the submitted work. IDP reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Aerocrine, personal fees from Almirall, personal fees from Novartis, personal fees from GlaxoSmithKline, personal fees from Genentech, personal fees from Regeneron, Teva, Chiesi, Sanofi, Circassia, Knopp, grants from NIHR, outside the submitted work. DY, CC, PA, DAH, KR, KC have nothing to disclose.</CoiStatement>
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