Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice
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PHARMACOGENETICS
Implementation and management outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in clinical practice Stefan Russmann 1,2,3,4 & Ali Rahmany 1,3,4 & David Niedrig 1,5 & Karl-Dietrich Hatz 6 & Katja Ludin 7 & Andrea M. Burden 4 & Lars Englberger 8 & Roland Backhaus 9 & Andreas Serra 2 & Markus Béchir 3 Received: 14 September 2020 / Accepted: 17 November 2020 # The Author(s) 2020
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 evidencebased 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. Keywords Pharmacogenetics . CYP2C19 . Clopidogrel . Cardiology . Clinical pharmacology
* Stefan Russmann [email protected] 1
drugsafety.ch, Seestrasse 221, 8700 Küsnacht, Switzerland
2
Institute of Internal Medicine and Nephrology, Clinic Hirslanden, Zurich, Switzerland
3
Center for Internal Medicine, Clinic Hirslanden, Aarau, Switzerland
4
Pharmaceutical Sciences, Swiss Federal Institute of Technology Zurich (ETHZ), Zurich, Switzerland
5
Hospital Pharmacy, Clinic Hirslanden, Zurich, Switzerland
6
INTLAB AG, Zurich, Switzerland
7
Labor Risch, Mocelular Genetics, Berne, Switzerland
8
Cardiac Surgery, Clinic Hirslanden, Aarau, Switzerland
9
Stroke Center and Clinic for Neurology, Clinic Hirsla
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