Real-World Implementation of CYP2C19 Pharmacogenetic Testing in Clopidogrel-Treated Patients: Insights from French Clinical Data

Real-World Implementation of CYP2C19 Pharmacogenetic Testing in Clopidogrel-Treated Patients: Insights from French Clinical Data | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Real-World Implementation of CYP2C19 Pharmacogenetic Testing in Clopidogrel-Treated Patients: Insights from French Clinical Data Alexandre Maes, Laura Gosselin, Aude Triquenot, Julien Bourgain, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9314427/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 10 You are reading this latest preprint version Abstract Clopidogrel is a highly prescribed antiplatelet prodrug that requires activation by CYP2C19. Loss-of-function variants, such as CYP2C19*2, may reduce its efficacy and increase the risk of cardiovascular events. This study aimed to evaluate the real-world implementation of CYP2C19 pharmacogenetic testing in patients treated with clopidogrel, using data from a French clinical data repository. Data were extracted from the EdSAN database, including patient demographics, prescribers, timing of testing, genotyping results and associated treatment changes. Of the 168 patients identified, 157 were included (mean age 72.4 years; male-to-female ratio 2.1). Neurologists were the main prescribers (95%). Testing was mainly carried out after the initiation of clopidogrel treatment. 62 patients carried a loss-of-function allele, which was frequently associated with a switch to lysine acetylsalicylate. These results highlight a gap between pharmacogenetic data and their implementation in routine clinical practice, which calls for earlier integration of CYP2C19 testing into therapeutic decision-making. Biological sciences/Computational biology and bioinformatics/Predictive medicine Health sciences/Risk factors clopidogrel pharmacogenetics CYP2C19 clinical data warehouse personalised medicine Figures Figure 1 1. Introduction Clopidogrel is a second generation antiplatelet drug and is one of the drugs most used to reduce the risk of myocardial infarction and stroke [ 1 ]. This drug has been on the market since 1997 and is on the World Health Organization essential medicine lists [ 2 ]. It is a thienopyridine prodrug that requires activation by hepatic biotransformation in cytochrome CYP2C19 to form an active metabolite that selectively and irreversibly inhibits platelet aggregation via inhibition of P2Y12 [ 3 , 4 ]. Some patients acquire clopidogrel resistance due to a CYP2C19 defect that is associated with a higher risk of relapse of cardiovascular disease [ 5 , 6 ]. Indeed in 2010, the Food and Drug Administration, in the product summary of clopidogrel, stated that pharmacogenetic testing of CYP2C19 could be used as an aid to assess therapeutic safety and to consider alternative strategies in patients with a predicted phenotype of clopidogrel resistance due to a CYP2C19 defect [ 7 , 8 ]. Moreover, a pharmacogenetic cause of resistance to clopidogrel was established with the demonstration of decreased CYP2C19 enzymatic activity due to certain genetic variants. This defect led to high platelet reactivity and predicted altered phenotype and decreased anti-aggregant effect [ 7 ]. The CYP2C19 *2 allele (NM_000769.4:c.332-23A > G, rs4244285) is the most frequent CYP2C19 loss-of-function allele in European populations, with CYP2C19 *2 allele frequencies of approximately 12% in Europeans, 15% in African Americans, and 30% in Asian populations [ 9 ]. A patient is considered as resistant to clopidogrel due to pharmacogenetic factors in the presence of at least one CYP2C19 *2 allele (heterozygous) with a predicted phenotype of Intermediate Metaboliser (IM), with an additional effect if both alleles are CYP2C19 *2 (homozygous) with a predicted phenotype of Poor Metaboliser (PM) [ 4 , 10 ]. Other pharmacogenetic variants exist according to geographical and ethnic factors ( CYP2C19*3; CYP2C19*17) , for example the prevalence of the CYP2C19*3 allele is higher in Asian populations [ 11 ]. Patients with resistant phenotypes treated with clopidogrel have a higher risk of thrombotic disease [ 12 ]. In addition to pharmacogenetic factors, interindividual variability in response to clopidogrel, such as drug-drug interactions and drugs that inhibit CYP2C19 , can also explain resistance to clopidogrel [ 13 ]. CYP2C19 gene testing associated with P2Y12 inhibitor prescription could be beneficial in the prevention of cardiovascular diseases in order to propose the most appropriate treatment [ 14 , 15 ]. However, indications for ordering CYP2C19 tests with clopidogrel are not clear in the medical literature [ 16 ]. Proper guidelines are needed on the best time to order CYP2C19 tests: before drug prescription or after drug prescription. In this context, the real-life setting of CYP2C19 testing and drug prescription is of primary interest in healthcare systems. Clinical Data Warehouses (CDW) can be useful to obtain a snapshot of clinicians’ use of CYP2C19 testing [ 17 ]. The aim of this study was to evaluate the real-world implementation of CYP2C19 pharmacogenetic testing in patients treated with clopidogrel and its impact on clinical decision-making, based on a specific query in a clinical data warehouse, in France [ 18 ]. 2. Materials and Methods Study design This was a retrospective single centre cohort. The database of the CDW of Rouen University Hospital was searched to identify patients who had CYP2C19 testing and clopidogrel prescription between February, 2015 and October, 2022 (15). The search query was: (clopidogrel OR Plavix OR (clopidogrel (INN OR Plavix)) AND " CYP2C19 " OR "P2C19" OR "2C19" OR "cytochrome C19"OR (" CYP2C19 "OR "P2C19" OR "2C19" OR "cytochrome C19"~3). Patients and physician prescribers Patients and physicians were anonymised in the CDW. The following data were collected in an excel spreadsheet based on the study of Electronic Medical Records (EMR): characteristics of patients and physicians, indications for CYP2C19 testing, results of CYP2C19 testing, and therapeutic changes associated with CYP2C19 testing. Data collection and analysis were performed by two operators (AM and JW). Genotyping methods Pharmacogenetic testing was performed for the pharmacogenetic variant CYP2C19*2 (rs4244285) according to the standard operating procedure in our laboratory, based on TaqMan Polymerase Chain Reaction method [4]. Briefly, genomic DNA from whole blood was isolated using a QIAamp® DNA Blood Mini Kit (QIAGEN, Les Ulis, France) according to the manufacturer's instructions. CYP2C19 genotyping for rs4244285 G>A ( CYP2C19*2 ) was carried out by TaqMan® allelic discrimination assays (C__25986767_70) on an ABI PRISM 7000 Sequence Detection System (Applied Biosystems). Direct sequencing was used to validate internal quality controls corresponding to genomic DNA of each genotype. Amplification of sequences containing the target alleles was conducted using the following pairs of primers: forward 5′-TCTCTTGTCAGAATTTTCTTTCTCAA-3′/reverse 5′-TGAATCACAAATACGCAAGCA-3′ for the *2 allele. The wild-type form of the gene lacking *2 allele is represented by CYP2C19*1 [19]. The results of pharmacogenetic tests are delivered to clinicians via the laboratory informatics system and paper reports. Study Characteristics Patients Patients’ demographics, age and sex were evaluated. Physician prescribers The characteristics of physicians relative to ordering CYP2C19 tests were evaluated. CYP2C19 testing Patients were classified in NM (normal metabolisers), associated with CYP2C19*1/*1 , i.e. normal metabolisation of clopidogrel and optimal clopidogrel antiplatelet effect, intermediate metabolisers (IM) associated with CYP2C19*1/*2, i.e. subnormal metabolisation of clopidogrel, poor metabolisers (PM) associated with CYP2C19*2/*2, i.e. decreased metabolisation of clopidogrel. Patients with IM and PM status are CYP2C19 loss-of-function carriers, leading to clopidogrel resistance and consequently absence of clopidogrel antiplatelet effect. Timing indications The timing of the CYP2C19 test relative to the first clopidogrel prescription (before/after) was evaluated: (i) before clopidogrel prescription and (ii) after clopidogrel prescription. Therapeutic changes Therapeutic changes associated with CYP2C19 tests ( CYP2C19 *1/*2 plus CYP2C19 *2/*2) were evaluated. Statistical analysis Results are described as absolute values [min-max] and percentages. Chi-2 test was performed otherwise. 3. Results Patients Among 168 patients identified in the CDW, 157 patients were included in the study (figure 1). Eleven patients were not included because the results of CYP2C19 tests were not recorded in the EMR. The mean age of patients was 72.4 years [min = 46; max= 98]. The sex ratio was 2.1. The EMR of all patients were analysed, comprising 1994 reports, i.e., 11.9 reports per patient [min = 1; max = 145]. Among the 157 patients included, eight patients had other cardiovascular diseases than stroke, 128 patients had a CYP2C19 test after clopidogrel prescription, i.e. for stroke relapse on clopidogrel and 21 patients had a CYP2C19 test before clopidogrel prescription. Physician prescribers Among 128 of the 157 patients included, CYP2C19 tests were ordered by neurologists. For the remaining 29 patients, tests were ordered by physicians in the departments of geriatrics, hepato-gastro-enterology, vascular medicine, surgery, and internal medicine. CYP2C19 testing The results of CYP2C19 testing were: (i) 82 CYP2C19*1/*1 genotypes (NM), (ii) 51 CYP2C19*1/*2 genotypes (IM), (iii) 8 CYP2C19*2/*2 genotypes (PM) (Table 1). For 8 patients, who were tested for CYP2C19 genetics and who had an EMR, no result was retrieved. Only CYP2C19* 1 and CYP2C19* 2 alleles were identified in the study population; no CYP2C19*3 or CYP2C19* 17 alleles were observed. Thus, of the 141 patients for whom CYP2C19 results were available, 62 had CYP2C19 loss-of-function (Table 1). Among them, 59 patients had a stroke and 3 patients had other cardiovascular diseases. Of note, 5 patients were NM status and 3 patients were IM status in the group “Patients with other cardiovascular diseases” (Figure 1). Table 1 Results of CYP2C19 testing CYP2C19 testing Number CYP2C19*1/*1 87 CYP2C19*1/*2 54 CYP2C19*2/*2 8 Not retrieved 8 Total 157 Timing indications Among 128 of the 157 patients, CYP2C19 testing was ordered after clopidogrel prescription (Table 2). Among these 128 patients, 120 patients were on clopidogrel monotherapy, and 8 patients were on dual antiplatelet therapy (DAPT). Among 21 of the 157 patients, CYP2C19 testing was ordered before clopidogrel prescription. Among these 21 patients, 17 patients were on another antiplatelet such as lysine acetylsalicylate or aspirin, and 4 patients had clopidogrel for secondary prevention after a first stroke. 8 patients were not categorized in genotyping groups (Not retrieved). No difference was found between groups for the distribution of patients with NM, IM and PM based on the timing of CYP2C19 testing (Chi-2 test performed). Table 2 Timing indications among stroke patients according to results of CYP2C19 testing CYP2C19 testing CYP2C19*1/*1 CYP2C19*1/*2 CYP2C19*2/*2 Not retrieved Timing indications Before clopidogrel prescription 12(57.1%) 6(28.5%) 1(4.8%) 2(9.5%) 21 (14.1%) After clopidogrel prescription 70 (54.6%) 45(35.2%) 7(5.5%) 6(4.7%) 128 (85.9%) Total 149 (100%) 82 51 8 8 Therapeutic changes Among the 62 patients with CYP2C19 loss-of-function (Tables 1 and 2), 43 patients were switched to single antiplatelet therapy with lysine acetylsalicylate, 5 patients were switched to DAPT, and 3 patients were switched to anticoagulant. In a patient, the type of medication changed was not retrieved (other) (Table 3). Among the 82 patients with NM status, therapeutic changes were made for 69 of them, including 30 patients who were switched from clopidogrel to lysine acetylsalicylate, 24 were maintained on clopidogrel, 4 had DAPT, 1 was switched to an anticoagulant, 1 was switched from coumarin + aspirin to clopidogrel, and in 22 patients therapeutic changes were not retrieved. Table 3 Therapeutic changes in carriers of loss-of-function CYP2C19 CYP2C19 testing CYP2C19*1/*2 CYP2C19*2/*2 Total Therapeutic changes Maintenance of clopidogrel 4 0 4 Switch to aspirin or lysine acetylsalicylate 38 5 43 DAPT 4 1 5 Switch to anticoagulant 3 0 3 Other 0 1 1 NR (not retrieved) 5 1 6 Total 54 8 62 4. Discussion In our study, patients were predominantly over 70-year-old and mostly male. Neurologists were the main prescribers. Approximately four out of five patients had CYP2C19 testing after clopidogrel prescription. Around 40% of patients had a loss-of-function CYP2C19 allele ( CYP2C19*1/2 and CYP2C19*2/*2 ), associated with clopidogrel resistance. Therapeutic changes, with a switch of clopidogrel to lysine acetylsalicylate, were made for around 70% of carriers with loss-of-function CYP2C19 . Scientific evidence supports the clinical implementation of CYP2C19 testing before initiation of clopidogrel treatment as an effective approach for guiding early antiplatelet drug modifications in cardiovascular diseases. The positive impact of such measures has already been demonstrated for patients with high-risk acute coronary syndrome [ 20 ] and guidelines are starting to be published [ 21 – 23 ]. In our academic hospital, the results of CYP2C19 genotyping are accessible through the laboratory information system. Direct proposals for CYP2C19 testing linked to clopidogrel prescription via clinical decision support systems could accelerate the uptake of testing. A strength of our study is the real-life study of CYP2C19 testing associated with clopidogrel prescription. This provides a snapshot of CYP2C19 testing and clopidogrel since the test was set up in our academic hospital in 2015. The study sheds light on prescribers' profiles and their use of CYP2C19 testing in clopidogrel prescription. Another strength of this study lies in the fact that patients on clopidogrel with CYP2C19 loss-of-function face a significant risk of adverse reactions due to a lack of CYP2C19 testing. In our study, most carriers of CYP2C19 loss-of-function who were on clopidogrel were switched to single antiplatelet therapy when a CYP2C19*2 allele was detected. The main limitation of our study was the low number of CYP2C19 genetic tests performed. Factors contributing to this low number included the absence of clinical practice guidelines for CYP2C19 genetics for clopidogrel and the lack of reimbursement of CYP2C19 testing in France, which are barriers to implementing these tests. Despite the high prescription numbers of clopidogrel in France (300,000 patients annually), fewer than 500 patients had CYP2C19 testing for antiplatelet therapy in 2022, according to the Agence de Biomedicine[ 24 ] [ 25 ]. Several solutions could facilitate CYP2C19 testing: (i) pharmacist-led ordering could improve CYP2C19 testing [ 26 ], (ii) educating physicians in CYP2C19 testing and (iii) implementing point-of-care CYP2C19 testing at the bedside, enabling quicker therapeutic adjustments [ 27 ]. Our study could contribute to evidence-based public health decisions aimed at preventive interventions in clopidogrel treatment, emphasising the need for preemptive CYP2C19 testing in patients treated with clopidogrel. Conclusion Among perspectives, we need to integrate CYP2C19 genetic data in EMR with a clinical decision support system to aid efficient clopidogrel prescription based on CYP2C19 testing [ 28 ]. Clear European multidisciplinary clinical practice guidelines must position pharmacogenetics of CYP2C19 for the benefit of patients with stroke and other cardiovascular diseases. Declarations Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request, subject to institutional and ethical restrictions. Supplementary Information: The online version contains supplementary material available Acknowledgments: The authors are grateful to Nikki Sabourin-Gibbs, CHU Rouen, for her help in editing the manuscript. Author Contribution: Conceptualization: Alexandre Maes, Laura Gosselin, Aude Triquenot, Julien Bourgain,Stéfan Darmoni, Julien Grosjean, Fabien Lamoureux, Julien Wils; Methodology: Alexandre Maes, Julien Wils, with support from Laura Gosselin; Formal analysis and investigation: Alexandre Maes, with validation by Julien Wils; Writing – original draft preparation: Alexandre Maes; Writing – review and editing: Julien Wils; Resources: Alexandre Maes, Laura Gosselin, Aude Triquenot, Julien Bourgain,Stéfan Darmoni, Julien Grosjean, Fabien Lamoureux, Julien Wils; Supervision: Julien Wils. All authors critically reviewed the manuscript and approved the final version. Competing Interests: The authors have no competing interests to declare that are relevant to the content of this article. Human ethics approval: The study used data retrieved from the local CDW. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9314427","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":620369900,"identity":"96688b00-1e26-46de-85d5-f5496c38ff88","order_by":0,"name":"Alexandre Maes","email":"data:image/png;base64,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","orcid":"https://orcid.org/0009-0006-2873-928X","institution":"CHU Rouen Normandie","correspondingAuthor":true,"prefix":"","firstName":"Alexandre","middleName":"","lastName":"Maes","suffix":""},{"id":620369901,"identity":"6c2b528e-94b4-40b6-8dd4-138eac92bd41","order_by":1,"name":"Laura Gosselin","email":"","orcid":"","institution":"CHU Rouen Normandie","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Gosselin","suffix":""},{"id":620369902,"identity":"eb901de1-e5a2-4891-9875-90c76110694e","order_by":2,"name":"Aude Triquenot","email":"","orcid":"","institution":"CHU Rouen Normandie","correspondingAuthor":false,"prefix":"","firstName":"Aude","middleName":"","lastName":"Triquenot","suffix":""},{"id":620369903,"identity":"6941f2a3-8918-4785-abf1-7b559adba241","order_by":3,"name":"Julien Bourgain","email":"","orcid":"","institution":"CHU Rouen Normandie","correspondingAuthor":false,"prefix":"","firstName":"Julien","middleName":"","lastName":"Bourgain","suffix":""},{"id":620369904,"identity":"04be49a9-e5d4-4850-a341-b20e441b07b0","order_by":4,"name":"Stéfan Darmoni","email":"","orcid":"","institution":"CHU Rouen Normandie","correspondingAuthor":false,"prefix":"","firstName":"Stéfan","middleName":"","lastName":"Darmoni","suffix":""},{"id":620369905,"identity":"c484e688-1484-4154-9bfd-b0238a3678b7","order_by":5,"name":"Julien Grosjean","email":"","orcid":"","institution":"CHU Rouen Normandie","correspondingAuthor":false,"prefix":"","firstName":"Julien","middleName":"","lastName":"Grosjean","suffix":""},{"id":620369906,"identity":"e02e7b90-0986-4e5d-a272-25f43e31829c","order_by":6,"name":"Fabien Lamoureux","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Fabien","middleName":"","lastName":"Lamoureux","suffix":""},{"id":620369907,"identity":"b1600e79-1ea5-4979-b7e2-fb2a346b0370","order_by":7,"name":"Julien Wils","email":"","orcid":"","institution":"CHU Rouen Normandie","correspondingAuthor":false,"prefix":"","firstName":"Julien","middleName":"","lastName":"Wils","suffix":""}],"badges":[],"createdAt":"2026-04-03 15:25:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9314427/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9314427/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107255724,"identity":"cf716b8d-0e2c-4b5c-92f1-b964ce8b6ce5","added_by":"auto","created_at":"2026-04-19 12:11:41","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":74210,"visible":true,"origin":"","legend":"\u003cp\u003eFlow-chart of patients with \u003cem\u003eCYP2C19\u003c/em\u003e testing and clopidogrel prescription\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9314427/v1/437e1cd23b8d6b6ce5988c21.png"},{"id":107482446,"identity":"0e475e28-48b0-4ca4-81b9-accfd7b7d61d","added_by":"auto","created_at":"2026-04-22 02:23:35","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":430097,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9314427/v1/6a91805d-187c-4377-a9e5-79089e281a52.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Real-World Implementation of CYP2C19 Pharmacogenetic Testing in Clopidogrel-Treated Patients: Insights from French Clinical Data","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eClopidogrel is a second generation antiplatelet drug and is one of the drugs most used to reduce the risk of myocardial infarction and stroke [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This drug has been on the market since 1997 and is on the World Health Organization essential medicine lists [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. It is a thienopyridine prodrug that requires activation by hepatic biotransformation in cytochrome \u003cem\u003eCYP2C19\u003c/em\u003e to form an active metabolite that selectively and irreversibly inhibits platelet aggregation via inhibition of P2Y12 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Some patients acquire clopidogrel resistance due to a \u003cem\u003eCYP2C19\u003c/em\u003e defect that is associated with a higher risk of relapse of cardiovascular disease [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Indeed in 2010, the Food and Drug Administration, in the product summary of clopidogrel, stated that pharmacogenetic testing of \u003cem\u003eCYP2C19\u003c/em\u003e could be used as an aid to assess therapeutic safety and to consider alternative strategies in patients with a predicted phenotype of clopidogrel resistance due to a \u003cem\u003eCYP2C19\u003c/em\u003e defect [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Moreover, a pharmacogenetic cause of resistance to clopidogrel was established with the demonstration of decreased \u003cem\u003eCYP2C19\u003c/em\u003e enzymatic activity due to certain genetic variants. This defect led to high platelet reactivity and predicted altered phenotype and decreased anti-aggregant effect [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The \u003cem\u003eCYP2C19\u003c/em\u003e*2 allele (NM_000769.4:c.332-23A\u0026thinsp;\u0026gt;\u0026thinsp;G, rs4244285) is the most frequent \u003cem\u003eCYP2C19\u003c/em\u003e loss-of-function allele in European populations, with \u003cem\u003eCYP2C19\u003c/em\u003e*2 allele frequencies of approximately 12% in Europeans, 15% in African Americans, and 30% in Asian populations [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. A patient is considered as resistant to clopidogrel due to pharmacogenetic factors in the presence of at least one \u003cem\u003eCYP2C19\u003c/em\u003e*2 allele (heterozygous) with a predicted phenotype of Intermediate Metaboliser (IM), with an additional effect if both alleles are \u003cem\u003eCYP2C19\u003c/em\u003e*2 (homozygous) with a predicted phenotype of Poor Metaboliser (PM) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Other pharmacogenetic variants exist according to geographical and ethnic factors (\u003cem\u003eCYP2C19*3; CYP2C19*17)\u003c/em\u003e, for example the prevalence of the \u003cem\u003eCYP2C19*3\u003c/em\u003e allele is higher in Asian populations [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Patients with resistant phenotypes treated with clopidogrel have a higher risk of thrombotic disease [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In addition to pharmacogenetic factors, interindividual variability in response to clopidogrel, such as drug-drug interactions and drugs that inhibit \u003cem\u003eCYP2C19\u003c/em\u003e, can also explain resistance to clopidogrel [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. \u003cem\u003eCYP2C19\u003c/em\u003e gene testing associated with P2Y12 inhibitor prescription could be beneficial in the prevention of cardiovascular diseases in order to propose the most appropriate treatment [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. However, indications for ordering \u003cem\u003eCYP2C19\u003c/em\u003e tests with clopidogrel are not clear in the medical literature [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Proper guidelines are needed on the best time to order \u003cem\u003eCYP2C19\u003c/em\u003e tests: before drug prescription or after drug prescription. In this context, the real-life setting of \u003cem\u003eCYP2C19\u003c/em\u003e testing and drug prescription is of primary interest in healthcare systems. Clinical Data Warehouses (CDW) can be useful to obtain a snapshot of clinicians\u0026rsquo; use of \u003cem\u003eCYP2C19\u003c/em\u003e testing [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe aim of this study was to evaluate the real-world implementation of CYP2C19 pharmacogenetic testing in patients treated with clopidogrel and its impact on clinical decision-making, based on a specific query in a clinical data warehouse, in France [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis was a retrospective single centre cohort. The database of the CDW of Rouen University Hospital was searched to identify patients who had \u003cem\u003eCYP2C19\u003c/em\u003e testing and clopidogrel prescription between February, 2015 and October, 2022 (15). The search query was: (clopidogrel OR Plavix OR (clopidogrel (INN OR Plavix)) AND \u0026quot;\u003cem\u003eCYP2C19\u003c/em\u003e\u0026quot; OR \u0026quot;P2C19\u0026quot; OR \u0026quot;2C19\u0026quot; OR \u0026quot;cytochrome C19\u0026quot;OR (\u0026quot;\u003cem\u003eCYP2C19\u003c/em\u003e\u0026quot;OR \u0026quot;P2C19\u0026quot; OR \u0026quot;2C19\u0026quot; OR \u0026quot;cytochrome C19\u0026quot;~3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients and physician prescribers\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients and physicians were anonymised in the CDW. The following data were collected in an excel spreadsheet based on the study of\u0026nbsp;Electronic Medical Records (EMR): characteristics of patients and physicians, indications\u0026nbsp;for \u003cem\u003eCYP2C19\u003c/em\u003e testing, results of \u003cem\u003eCYP2C19\u003c/em\u003e testing, and therapeutic changes associated with \u003cem\u003eCYP2C19\u003c/em\u003e testing. Data collection and analysis were performed by two operators (AM and JW).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGenotyping methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePharmacogenetic testing was performed for the pharmacogenetic variant \u003cem\u003eCYP2C19*2\u003c/em\u003e (rs4244285) according to the standard operating procedure in our laboratory, based on TaqMan Polymerase Chain Reaction method [4]. Briefly, genomic DNA from whole blood was isolated using a QIAamp\u0026reg; DNA Blood Mini Kit (QIAGEN, Les Ulis, France) according to the manufacturer\u0026apos;s instructions. \u003cem\u003eCYP2C19\u003c/em\u003e genotyping for rs4244285 G\u0026gt;A (\u003cem\u003eCYP2C19*2\u003c/em\u003e) was carried out by TaqMan\u0026reg; allelic discrimination assays (C__25986767_70) on an ABI PRISM 7000 Sequence Detection System (Applied Biosystems). Direct sequencing was used to validate internal quality controls corresponding to genomic DNA of each genotype. Amplification of sequences containing the target alleles was conducted using the following pairs of primers: forward 5\u0026prime;-TCTCTTGTCAGAATTTTCTTTCTCAA-3\u0026prime;/reverse 5\u0026prime;-TGAATCACAAATACGCAAGCA-3\u0026prime; for the \u003cem\u003e*2\u003c/em\u003e allele. The wild-type form of the gene lacking *2 allele is represented by \u003cem\u003eCYP2C19*1\u003c/em\u003e [19].\u003c/p\u003e\n\u003cp\u003eThe results of pharmacogenetic tests are delivered to clinicians via the laboratory informatics system and paper reports.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy Characteristics\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatients\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients\u0026rsquo; demographics, age and sex were evaluated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePhysician prescribers\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The characteristics of physicians relative to ordering \u003cem\u003eCYP2C19\u003c/em\u003e tests were evaluated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCYP2C19 testing\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients were classified in NM (normal metabolisers), associated with \u003cem\u003eCYP2C19*1/*1\u003c/em\u003e, \u003cem\u003ei.e.\u003c/em\u003e normal metabolisation of clopidogrel and optimal clopidogrel antiplatelet effect, intermediate metabolisers (IM) associated with \u003cem\u003eCYP2C19*1/*2,\u003c/em\u003e \u003cem\u003ei.e.\u003c/em\u003e subnormal metabolisation of clopidogrel, poor metabolisers (PM) associated with \u003cem\u003eCYP2C19*2/*2,\u003c/em\u003e \u003cem\u003ei.e.\u003c/em\u003e decreased metabolisation of clopidogrel.\u003c/p\u003e\n\u003cp\u003ePatients with IM and PM status are \u003cem\u003eCYP2C19\u003c/em\u003e loss-of-function carriers, leading to clopidogrel resistance and consequently absence of clopidogrel antiplatelet effect.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTiming indications\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe timing of the \u003cem\u003eCYP2C19\u003c/em\u003e test relative to the first clopidogrel prescription (before/after) was evaluated: (i) before clopidogrel prescription and (ii) after clopidogrel prescription.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTherapeutic changes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTherapeutic changes associated with \u003cem\u003eCYP2C19\u003c/em\u003e tests (\u003cem\u003eCYP2C19\u003c/em\u003e*1/*2 plus \u003cem\u003eCYP2C19\u003c/em\u003e*2/*2) were evaluated.\u003c/p\u003e\n\u003cp id=\"_Toc142471694\"\u003eStatistical\u0026nbsp;analysis\u003c/p\u003e\n\u003cp\u003eResults are described as absolute values [min-max] and percentages. Chi-2 test was performed otherwise.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003ePatients\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong 168 patients identified in the CDW, 157 patients were included in the study (figure 1). Eleven patients were not included because the results of \u003cem\u003eCYP2C19\u003c/em\u003e tests were not recorded in the EMR. The mean age of patients was 72.4 years [min = 46; max= 98]. The sex ratio was 2.1. The EMR of all patients were analysed, comprising 1994 reports, \u003cem\u003ei.e.,\u003c/em\u003e 11.9 reports per patient [min = 1; max = 145]. Among the 157 patients included, eight patients had other cardiovascular diseases than stroke, 128 patients had a \u003cem\u003eCYP2C19\u003c/em\u003e test after clopidogrel prescription, \u003cem\u003ei.e.\u0026nbsp;\u003c/em\u003efor stroke relapse on clopidogrel and 21 patients had a \u003cem\u003eCYP2C19\u003c/em\u003e test before clopidogrel prescription.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePhysician prescribers\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Among 128 of the 157 patients included, \u003cem\u003eCYP2C19\u003c/em\u003e tests were ordered by neurologists. For the remaining 29 patients, tests were ordered by physicians in the departments of geriatrics, hepato-gastro-enterology, vascular medicine, surgery, and internal medicine.\u003c/p\u003e\n\u003cp\u003eCYP2C19 testing\u003c/p\u003e\n\u003cp\u003eThe results of CYP2C19 testing were: (i) 82 \u003cem\u003eCYP2C19*1/*1\u003c/em\u003e genotypes (NM), (ii) 51 \u003cem\u003eCYP2C19*1/*2\u003c/em\u003e genotypes (IM), (iii) 8 \u003cem\u003eCYP2C19*2/*2\u003c/em\u003e genotypes (PM) (Table 1). For 8 patients, who were tested for CYP2C19 genetics and who had an EMR, no result was retrieved. Only \u003cem\u003eCYP2C19*\u003cem\u003e1 and\u0026nbsp;\u003c/em\u003eCYP2C19*\u003cem\u003e2 alleles were identified in the study population; no CYP2C19*3 or\u0026nbsp;\u003c/em\u003eCYP2C19*\u003cem\u003e17 alleles were observed.\u003c/em\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThus, of the 141 patients for whom \u003cem\u003eCYP2C19\u003c/em\u003e results were available, 62 had CYP2C19 loss-of-function (Table 1). Among them, 59 patients had a stroke and 3 patients had other cardiovascular diseases. Of note, 5 patients were NM status and 3 patients were IM status in the group \u0026ldquo;Patients with other cardiovascular diseases\u0026rdquo; (Figure 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Results of \u003cem\u003eCYP2C19\u003c/em\u003e testing\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"528\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 41.0985%;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19\u003c/em\u003e testing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 58.9015%;\"\u003e\n \u003cp\u003eNumber\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41.0985%;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19*1/*1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58.9015%;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41.0985%;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19*1/*2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58.9015%;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41.0985%;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19*2/*2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58.9015%;\"\u003e\n \u003cp\u003e8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41.0985%;\"\u003e\n \u003cp\u003eNot retrieved\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58.9015%;\"\u003e\n \u003cp\u003e8\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 41.0985%;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58.9015%;\"\u003e\n \u003cp\u003e157\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp id=\"_Toc142471698\"\u003eTiming indications\u003c/p\u003e\n\u003cp\u003eAmong 128 of the 157 patients, \u003cem\u003eCYP2C19\u003c/em\u003e testing was ordered after clopidogrel prescription (Table 2). Among these 128 patients, 120 patients were on clopidogrel monotherapy, and 8 patients were on dual antiplatelet therapy (DAPT).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong 21 of the 157 patients, \u003cem\u003eCYP2C19\u003c/em\u003e testing was ordered before clopidogrel prescription. Among these 21 patients, 17 patients were on another antiplatelet such as lysine acetylsalicylate or aspirin, and 4 patients had clopidogrel for secondary prevention after a first stroke. 8 patients were not categorized in genotyping groups (Not retrieved).\u003c/p\u003e\n\u003cp\u003eNo difference was found between groups for the distribution of patients with NM, IM and PM based on the timing of \u003cem\u003eCYP2C19\u003c/em\u003e testing (Chi-2 test performed).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Timing indications among stroke patients according to results of \u003cem\u003eCYP2C19\u003c/em\u003e testing\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"516\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 389px;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19\u003c/em\u003e testing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19*1/*1\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19*1/*2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19*2/*2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003eNot retrieved\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003eTiming indications\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 102px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003eBefore clopidogrel prescription\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 102px;\"\u003e\n \u003cp\u003e12(57.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 98px;\"\u003e\n \u003cp\u003e6(28.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 98px;\"\u003e\n \u003cp\u003e1(4.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 91px;\"\u003e\n \u003cp\u003e2(9.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e21 (14.1%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003eAfter clopidogrel prescription\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 102px;\"\u003e\n \u003cp\u003e70 (54.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 98px;\"\u003e\n \u003cp\u003e45(35.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 98px;\"\u003e\n \u003cp\u003e7(5.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 91px;\"\u003e\n \u003cp\u003e6(4.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003e128 (85.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 127px;\"\u003e\n \u003cp\u003eTotal 149 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 102px;\"\u003e\n \u003cp\u003e82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTherapeutic changes\u003c/p\u003e\n\u003cp\u003eAmong the 62 patients with \u003cem\u003eCYP2C19\u003c/em\u003e loss-of-function (Tables 1 and 2), 43 patients were switched to single antiplatelet therapy with lysine acetylsalicylate, 5 patients were switched to DAPT, and 3 patients were switched to anticoagulant. In a patient, the type of medication changed was not retrieved (other) (Table 3).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong the 82 patients with NM status, therapeutic changes were made for 69 of them, including 30 patients who were switched from clopidogrel to lysine acetylsalicylate, 24 were maintained on clopidogrel, 4 had DAPT, 1 was switched to an anticoagulant, 1 was switched from coumarin + aspirin to clopidogrel, and in 22 patients therapeutic changes were not retrieved.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Therapeutic changes in carriers of loss-of-function \u003cem\u003eCYP2C19\u003c/em\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"596\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 157px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 343px;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19\u003c/em\u003e testing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19*1/*2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 158px;\"\u003e\n \u003cp\u003e\u003cem\u003eCYP2C19*2/*2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003eTherapeutic changes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 158px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 96px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003eMaintenance of clopidogrel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 185px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 158px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003eSwitch to aspirin or lysine acetylsalicylate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 185px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 158px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003eDAPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 185px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 158px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003eSwitch to anticoagulant\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 185px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 158px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003eOther\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 185px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 158px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003eNR (not retrieved)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 185px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 158px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 157px;\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 185px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 158px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 96px;\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn our study, patients were predominantly over 70-year-old and mostly male. Neurologists were the main prescribers. Approximately four out of five patients had \u003cem\u003eCYP2C19\u003c/em\u003e testing after clopidogrel prescription. Around 40% of patients had a loss-of-function \u003cem\u003eCYP2C19\u003c/em\u003e allele (\u003cem\u003eCYP2C19*1/2\u003c/em\u003e and \u003cem\u003eCYP2C19*2/*2\u003c/em\u003e), associated with clopidogrel resistance. Therapeutic changes, with a switch of clopidogrel to lysine acetylsalicylate, were made for around 70% of carriers with loss-of-function \u003cem\u003eCYP2C19\u003c/em\u003e.\u003c/p\u003e \u003cp\u003eScientific evidence supports the clinical implementation of \u003cem\u003eCYP2C19\u003c/em\u003e testing before initiation of clopidogrel treatment as an effective approach for guiding early antiplatelet drug modifications in cardiovascular diseases. The positive impact of such measures has already been demonstrated for patients with high-risk acute coronary syndrome [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and guidelines are starting to be published [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In our academic hospital, the results of \u003cem\u003eCYP2C19\u003c/em\u003e genotyping are accessible through the laboratory information system. Direct proposals for \u003cem\u003eCYP2C19\u003c/em\u003e testing linked to clopidogrel prescription via clinical decision support systems could accelerate the uptake of testing.\u003c/p\u003e \u003cp\u003eA strength of our study is the real-life study of \u003cem\u003eCYP2C19\u003c/em\u003e testing associated with clopidogrel prescription. This provides a snapshot of \u003cem\u003eCYP2C19\u003c/em\u003e testing and clopidogrel since the test was set up in our academic hospital in 2015. The study sheds light on prescribers' profiles and their use of \u003cem\u003eCYP2C19\u003c/em\u003e testing in clopidogrel prescription.\u003c/p\u003e \u003cp\u003eAnother strength of this study lies in the fact that patients on clopidogrel with \u003cem\u003eCYP2C19\u003c/em\u003e loss-of-function face a significant risk of adverse reactions due to a lack of \u003cem\u003eCYP2C19\u003c/em\u003e testing. In our study, most carriers \u003cem\u003eof CYP2C19\u003c/em\u003e loss-of-function who were on clopidogrel were switched to single antiplatelet therapy when a \u003cem\u003eCYP2C19*2\u003c/em\u003e allele was detected.\u003c/p\u003e \u003cp\u003eThe main limitation of our study was the low number of \u003cem\u003eCYP2C19\u003c/em\u003e genetic tests performed. Factors contributing to this low number included the absence of clinical practice guidelines for \u003cem\u003eCYP2C19\u003c/em\u003e genetics for clopidogrel and the lack of reimbursement of \u003cem\u003eCYP2C19\u003c/em\u003e testing in France, which are barriers to implementing these tests. Despite the high prescription numbers of clopidogrel in France (300,000 patients annually), fewer than 500 patients had \u003cem\u003eCYP2C19\u003c/em\u003e testing for antiplatelet therapy in 2022, according to the Agence de Biomedicine[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral solutions could facilitate \u003cem\u003eCYP2C19\u003c/em\u003e testing: (i) pharmacist-led ordering could improve \u003cem\u003eCYP2C19\u003c/em\u003e testing [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], (ii) educating physicians in \u003cem\u003eCYP2C19\u003c/em\u003e testing and (iii) implementing point-of-care \u003cem\u003eCYP2C19\u003c/em\u003e testing at the bedside, enabling quicker therapeutic adjustments [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eOur study could contribute to evidence-based public health decisions aimed at preventive interventions in clopidogrel treatment, emphasising the need for preemptive \u003cem\u003eCYP2C19\u003c/em\u003e testing in patients treated with clopidogrel.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAmong perspectives, we need to integrate \u003cem\u003eCYP2C19\u003c/em\u003e genetic data in EMR with a clinical decision support system to aid efficient clopidogrel prescription based on \u003cem\u003eCYP2C19\u003c/em\u003e testing [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Clear European multidisciplinary clinical practice guidelines must position pharmacogenetics of \u003cem\u003eCYP2C19\u003c/em\u003e for the benefit of patients with stroke and other cardiovascular diseases.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available from the corresponding author upon reasonable request, subject to institutional and ethical restrictions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary Information:\u0026nbsp;\u003c/strong\u003eThe online version contains supplementary material available\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e The authors are grateful to Nikki Sabourin-Gibbs, CHU Rouen, for her help in editing the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution:\u003c/strong\u003e\u0026nbsp; Conceptualization: Alexandre Maes, Laura Gosselin, Aude Triquenot, Julien Bourgain,St\u0026eacute;fan Darmoni, Julien Grosjean, Fabien Lamoureux, Julien Wils; Methodology: Alexandre Maes, Julien Wils, with support from Laura Gosselin; Formal analysis and investigation: Alexandre Maes, with validation by Julien Wils; Writing \u0026ndash; original draft preparation: Alexandre Maes; Writing \u0026ndash; review and editing: Julien Wils; Resources: Alexandre Maes, Laura Gosselin, Aude Triquenot, Julien Bourgain,St\u0026eacute;fan Darmoni, Julien Grosjean, Fabien Lamoureux, Julien Wils; Supervision: Julien Wils. All authors critically reviewed the manuscript and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e The authors have no competing interests to declare that are relevant to the content of this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman ethics approval:\u0026nbsp;\u003c/strong\u003eThe study used data retrieved from the local CDW. It was approved by the local ethics committee which stated that the research was outside of the field of the Jard\u0026eacute; Law (French Law regulating human research).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate:\u003c/strong\u003e Patient consent was waived due to the retrospective nature of the study and the use of anonymised data from the clinical data warehouse.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e Not applicable\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBeavers CJ, Naqvi IA. Clopidogrel. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Sept 7]. http://www.ncbi.nlm.nih.gov/books/NBK470539/. Accessed 7 Sept 2023\u003c/li\u003e\n\u003cli\u003eWHO Model Lists of Essential Medicines [Internet]. 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Clinical Pharmacogenetics Implementation Consortium Guideline for \u003cem\u003eCYP2C19\u003c/em\u003e Genotype and Clopidogrel Therapy: 2022 Update. Clin Pharmacol Ther. 2022;112:959\u0026ndash;67. https://doi.org/10.1002/cpt.2526\u003c/li\u003e\n\u003cli\u003eIonova Y, Ashenhurst J, Zhan J, Nhan H, Kosinski C, Tamraz B, et al. CYP2C19 Allele Frequencies in Over 2.2 Million Direct-to-Consumer Genetics Research Participants and the Potential Implication for Prescriptions in a Large Health System. Clin Transl Sci. 2020;13:1298\u0026ndash;306. https://doi.org/10.1111/cts.12830\u003c/li\u003e\n\u003cli\u003eMao L, Jian C, Changzhi L, Dan H, Suihua H, Wenyi T, et al. Cytochrome CYP2C19 polymorphism and risk of adverse clinical events in clopidogrel-treated patients: a meta-analysis based on 23,035 subjects. Arch Cardiovasc Dis. 2013;106:517\u0026ndash;27. https://doi.org/10.1016/j.acvd.2013.06.055\u003c/li\u003e\n\u003cli\u003eCytochrome P450 2C19 Inhibitor - an overview | ScienceDirect Topics [Internet]. [cited 2023 Dec 18]. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/cytochrome-p450-2c19-inhibitor. Accessed 18 Dec 2023\u003c/li\u003e\n\u003cli\u003eRoden DM. Clopidogrel Pharmacogenetics - Why the Wait? N Engl J Med. 2019;381:1677\u0026ndash;8. https://doi.org/10.1056/NEJMe1911496\u003c/li\u003e\n\u003cli\u003eWang Y, Meng X, Wang A, Xie X, Pan Y, Johnston SC, et al. Ticagrelor versus Clopidogrel in CYP2C19 Loss-of-Function Carriers with Stroke or TIA. N Engl J Med. Massachusetts Medical Society; 2021;385:2520\u0026ndash;30. https://doi.org/10.1056/NEJMoa2111749\u003c/li\u003e\n\u003cli\u003eTAILOR-PCI: Genotype-guided Antiplatelet Therapy Post PCI Misses Mark [Internet]. Am. Coll. Cardiol. [cited 2026 Jan 21]. https://www.acc.org/Latest-in-Cardiology/Articles/2020/03/24/16/41/http%3a%2f%2fwww.acc.org%2fLatest-in-Cardiology%2fArticles%2f2020%2f03%2f24%2f16%2f41%2fsat-9am-TAILOR-PCI-Clinical-Implementation-Clopidogrel-Pharmacogenetics-acc-2020. Accessed 21 Jan 2026\u003c/li\u003e\n\u003cli\u003eMonnin P, Legrand J, Husson G, Ringot P, Tchechmedjiev A, Jonquet C, et al. PGxO and PGxLOD: a reconciliation of pharmacogenomic knowledge of various provenances, enabling further comparison. BMC Bioinformatics. 2019;20:139. https://doi.org/10.1186/s12859-019-2693-9\u003c/li\u003e\n\u003cli\u003ePressat-Laffouilh\u0026egrave;re T, Balay\u0026eacute; P, Dahamna B, Lelong R, Billey K, Darmoni SJ, et al. Evaluation of Doc\u0026rsquo;EDS: A French Semantic Search Tool to Query Health Documents from a Clinical Data Warehouse. BMC Med Inf Decis Mak. 2022;22:34,. https://doi.org/10.1186/s12911-022-01762-4.\u003c/li\u003e\n\u003cli\u003eLamoureux F, Duflot T, Woillard J-B, Metsu D, Pereira T, Compagnon P, et al. Impact of \u003cem\u003eCYP2C19\u003c/em\u003e genetic polymorphisms on voriconazole dosing and exposure in adult patients with invasive fungal infections. Int J Antimicrob Agents. 2016;47:124\u0026ndash;31. https://doi.org/10.1016/j.ijantimicag.2015.12.003\u003c/li\u003e\n\u003cli\u003eJiang M, You JHS. Review of Pharmacoeconomic Evaluation of Genotype-Guided Antiplatelet Therapy. Expert Opin Pharmacother. 2015;16:771-779,. https://doi.org/10.1517/14656566.2015.1013028.\u003c/li\u003e\n\u003cli\u003evan den Broek WWA, Ingraham BS, Pereira NL, Lee CR, Cavallari LH, Swen JJ, et al. Genotype-Guided Antiplatelet Therapy: JACC Review Topic of the Week. J Am Coll Cardiol. 2024;84:1107\u0026ndash;18. https://doi.org/10.1016/j.jacc.2024.06.038\u003c/li\u003e\n\u003cli\u003eDello Russo C, Frater I, Kuruvilla R, Lip S, O\u0026rsquo;Neill H, Burke K, et al. CYP2C19 genotype testing for clopidogrel: A guideline developed by the UK Centre of Excellence in Regulatory Science and Innovation in Pharmacogenomics (CERSI-PGx). Br J Clin Pharmacol [Internet]. [cited 2026 Jan 6];n/a. https://doi.org/10.1002/bcp.70370\u003c/li\u003e\n\u003cli\u003eClaassens DMF, Vos GJA, Bergmeijer TO, Hermanides RS, Hof AWJ van \u0026rsquo;t, Harst P van der, et al. A Genotype-Guided Strategy for Oral P2Y12 Inhibitors in Primary PCI. N Engl J Med. Massachusetts Medical Society; 2019;381:1621\u0026ndash;31. https://doi.org/10.1056/NEJMoa1907096\u003c/li\u003e\n\u003cli\u003edata.ansm.sante.fr [Internet]. [cited 2024 Feb 27]. https://data.ansm.sante.fr/. Accessed 27 Feb 2024\u003c/li\u003e\n\u003cli\u003eAgence de la biom\u0026eacute;decine [Internet]. [cited 2024 Oct 25]. https://www.agence-biomedecine.fr/. Accessed 25 Oct 2024\u003c/li\u003e\n\u003cli\u003eAlMukdad S, Elewa H, Arafa S, Al-Badriyeh D. Short- and Long-Term Cost-Effectiveness Analysis of CYP2C19 Genotype-Guided Therapy, Universal Clopidogrel, versus Universal Ticagrelor in Post-Percutaneous Coronary Intervention Patients in Qatar. Int J Cardiol. 2021;331:27-34,. https://doi.org/10.1016/j.ijcard.2021.01.044.\u003c/li\u003e\n\u003cli\u003eBaudhuin LM, Train LJ, Goodman SG, Lane GE, Lennon RJ, Mathew V, et al. Point of Care CYP2C19 Genotyping after Percutaneous Coronary Intervention. Pharmacogenomics J. 2022;22:303-307,. https://doi.org/10.1038/s41397-022-00278-4.\u003c/li\u003e\n\u003cli\u003ePereira NL, Rihal CS, So DYF, Rosenberg Y, Lennon RJ, Mathew V, et al. Clopidogrel Pharmacogenetics. Circ Cardiovasc Interv. 2019;12:007811,. https://doi.org/10.1161/CIRCINTERVENTIONS.119.007811.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-pharmacogenomics-journal","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tpj","sideBox":"Learn more about [The Pharmacogenomics Journal](http://www.nature.com/tpj/)","snPcode":"41397","submissionUrl":"https://mts-tpj.nature.com/cgi-bin/main.plex","title":"The Pharmacogenomics Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"clopidogrel, pharmacogenetics, CYP2C19, clinical data warehouse, personalised medicine","lastPublishedDoi":"10.21203/rs.3.rs-9314427/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9314427/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eClopidogrel is a highly prescribed antiplatelet prodrug that requires activation by CYP2C19. Loss-of-function variants, such as CYP2C19*2, may reduce its efficacy and increase the risk of cardiovascular events. This study aimed to evaluate the real-world implementation of CYP2C19 pharmacogenetic testing in patients treated with clopidogrel, using data from a French clinical data repository.\u003c/p\u003e \u003cp\u003eData were extracted from the EdSAN database, including patient demographics, prescribers, timing of testing, genotyping results and associated treatment changes. Of the 168 patients identified, 157 were included (mean age 72.4 years; male-to-female ratio 2.1). Neurologists were the main prescribers (95%). Testing was mainly carried out after the initiation of clopidogrel treatment. 62 patients carried a loss-of-function allele, which was frequently associated with a switch to lysine acetylsalicylate.\u003c/p\u003e \u003cp\u003eThese results highlight a gap between pharmacogenetic data and their implementation in routine clinical practice, which calls for earlier integration of CYP2C19 testing into therapeutic decision-making.\u003c/p\u003e","manuscriptTitle":"Real-World Implementation of CYP2C19 Pharmacogenetic Testing in Clopidogrel-Treated Patients: Insights from French Clinical Data","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 12:11:37","doi":"10.21203/rs.3.rs-9314427/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2026-05-06T16:03:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-05-06T12:41:23+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-21T15:31:52+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-04-16T19:54:47+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-13T16:36:25+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-04-09T13:42:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-09T12:56:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Pharmacogenomics Journal","date":"2026-04-08T15:50:42+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2026-04-07T09:26:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-03T15:23:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-pharmacogenomics-journal","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"tpj","sideBox":"Learn more about [The Pharmacogenomics Journal](http://www.nature.com/tpj/)","snPcode":"41397","submissionUrl":"https://mts-tpj.nature.com/cgi-bin/main.plex","title":"The Pharmacogenomics Journal","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"933fbab4-0427-417c-a530-34d60ad05a76","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"revise","date":"2026-05-06T16:03:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-05-06T12:41:23+00:00","index":2,"fulltext":"This content is not available."}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":66021149,"name":"Biological sciences/Computational biology and bioinformatics/Predictive medicine"},{"id":66021150,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-05-06T16:06:08+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 12:11:37","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9314427","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9314427","identity":"rs-9314427","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}