CYP2C19 defines clopidogrel response in patients undergoing percutaneous neurointervention procedure


Resumen del trabajo presentado al 5th Symposium on Biomedical Research: "Advances and Perspectives In Pharmacology, Drug Toxicity and Pharmacogenetics", celebrado en Madrid del 15 al 16 de marzo de 2018.[Introduction]: Clopidogrel is a widely prescribed thienopyridine prodrug which inhibits platelet aggregation. It is prescribed to prevent atherothrombotic and thromboembolic events in patients who are given a stent implant in carotid, vertebral or cranial arteries. CYP2C19 is the most studied enzyme involved in clopidogrel metabolism. The most common CYP2C19 no function polymorphisms (*2 and *3) have been associated with hyporesponse to clopidogrel, showing lower levels of the active metabolite. On the contrary, the presence of the increased function allele (*17) has demonstrated enhanced platelet inhibition and clopidogrel hyperresponse.[Methods]: This observational retrospective study assessed antiplatelet response and clinical events after clopidogrel treatment in patients who underwent percutaneous neurointervention, related to CYP2C19 metabolizer status (normal (NM), intermediate/poor (IM-PM) and ultra-rapid (UM); inferred from *2, *3 and *17 allele determination by real-time PCR).[Results]: One hundred twenty-three patients were analysed, of which 83% had cardiovascular risk factors. The most common type of intervention was angioplasty with stent. According to the aggregation value, 58.7% of the patients were responders to clopidogrel; moreover, 4.1% required dose reduction and 12.2% change of treatment. CYP2C19 IM-PM had higher aggregation value (201.1 vs 137.6 NM, 149.4 UM, p<0.05) and lower response rate (37.5% vs. 69.8% NM, 61.1% UM), along with higher treatment change rate (25% vs. 5.7% NM, 10.5% UM). Moreover, 20% of the patients suffered from a subsequent clinical event. The highest ischemic events incidence occurred in NM (11.3% vs. 6.3% IM, 10.5% UM; p=0.358) and haemorrhagic events in UM (13.2% vs. 0% IM and 3.8% NM; p=0.041). No differences found regarding ischemic events’ onset time, while haemorrhagic events’ frequency in UM was higher with shorter onset time (p=0.047). Additionally, 53% of the patients were receiving concomitant treatment with proton-pump inhibitors (PPIs), which showed significantly higher aggregation value when compared to those not receiving PPI concomitant treatment (178.1 vs. 134.4; p=0.009).[Conclusion]: CYP2C19 no function and increased function alleles defined clopidogrel response. CYP2C19 genotyping and platelet reactivity quantification help to determine whether a patient could be at risk of ischemic or haemorrhagic event. CYP2C19 UM patients have increased bleeding risk after percutaneous neurointervention. Therapeutic recommendations should include an alternative therapeutic option in IM-PM or UM patients.M. Saiz-Rodriguez was co-financed by Consejería de Educación, Juventud y Deporte from Comunidad de Madrid and Fondo Social Europeo. D. Koller is co-financed by the H2020 Marie Sklodowska-Curie Innovative Training Network 721236 grant.Peer reviewe

Similar works

Full text



Full text is not available time updated on 4/18/2019

This paper was published in Digital.CSIC.

Having an issue?

Is data on this page outdated, violates copyrights or anything else? Report the problem now and we will take corresponding actions after reviewing your request.