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dc.contributor.author
Russmann, Stefan
dc.contributor.author
Rahmany, Ali
dc.contributor.author
Niedrig, David
dc.contributor.author
Hatz, Karl-Dietrich
dc.contributor.author
Ludin, Katja
dc.contributor.author
Burden, Andrea
dc.contributor.author
Englberger, Lars
dc.contributor.author
Backhaus, Roland
dc.contributor.author
Serra, Andreas
dc.contributor.author
Béchir, Markus
dc.date.accessioned
2021-04-12T07:06:05Z
dc.date.available
2020-12-01T08:05:06Z
dc.date.available
2020-12-01T12:29:23Z
dc.date.available
2021-04-12T07:06:05Z
dc.date.issued
2021-05
dc.identifier.issn
0031-6970
dc.identifier.issn
1432-1041
dc.identifier.other
10.1007/s00228-020-03050-4
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/453857
dc.identifier.doi
10.3929/ethz-b-000453857
dc.description.abstract
Purpose The antiplatelet prodrug clopidogrel is bioactivated by the polymorphic enzyme CYP2C19. Prospective clinical studies demonstrated an association between CYP2C19 loss of function (LoF) variants and an increased risk of thrombotic events under clopidogrel, but pharmacogenetic (PGx) testing is not frequently implemented in clinical practice. We report our experience with PGx-guided clopidogrel therapy with particular regard to clinically relevant patient management changes. Methods We conducted an observational study analyzing patients that underwent PGx testing for clopidogrel therapy at two Swiss hospitals. Primary outcome was the proportion of patients with clinically relevant PGx-based management recommendations and their implementation. The association of recurrent ischemic events under clopidogrel with CYP2C19 LoF variants and other factors was explored in a multivariate case-control analysis. Results Among 56 patients undergoing PGx testing, 18 (32.1%) were classified as CYP2C19 intermediate or poor metabolizers. This resulted in 17 recommendations for a change of antiplatelet therapy, which were implemented in 12 patients (70.1%). In the remaining five patients, specific reasons for non-implementation could be identified. Recurrent ischemic events under clopidogrel were associated with LoF variants (OR 2.2, 95% CI 0.3–14.4) and several cardiovascular risk factors. Associations were not statistically significant in our small study, but plausible and in line with estimates from large prospective studies. Conclusion PGx-guided clopidogrel therapy can identify patients with an elevated risk of ischemic events and offer evidence-based alternative treatments. Successful implementation in clinical practice requires a personalized interdisciplinary service that evaluates indications and additional risk factors, provides specific recommendations, and proactively follows their implementation.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Springer
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Pharmacogenetics
en_US
dc.subject
CYP2C19
en_US
dc.subject
Clopidogrel
en_US
dc.subject
Cardiology
en_US
dc.subject
Clinical pharmacology
en_US
dc.title
Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2020-11-26
ethz.journal.title
European Journal of Clinical Pharmacology
ethz.journal.volume
77
en_US
ethz.journal.issue
5
en_US
ethz.journal.abbreviated
Eur J Clin Pharmacol
ethz.pages.start
709
en_US
ethz.pages.end
716
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Berlin
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::09633 - Burden, Andrea / Burden, Andrea
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::09633 - Burden, Andrea / Burden, Andrea
en_US
ethz.date.deposited
2020-12-01T08:05:17Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2021-04-12T07:06:20Z
ethz.rosetta.lastUpdated
2022-03-29T06:29:00Z
ethz.rosetta.versionExported
true
ethz.COinS
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