415 Correlation of Platelet Reactivity Testing and CYP2C19 Metabolizer Status in Patients Undergoing Endovascular Neurointervention. (1st April 2022)

• Record Type: Journal Article
• Authors: Benish, Alam; Lucke-Wold, Brandon; Laurent, Dimitri; Elchynski, Amanda; Cicali, Emily; Wiisanen, Kristin; Cavallari, Larissa; Hoh, Brian L.
• Is Part Of: Neurosurgery. Volume 68(2022)Supplement 1
• Page Start: 96
• Page End: 97
• Publication Date: 2022-04-01
• Subjects: Nervous system -- Surgery -- Periodicals; 617.48005
• DOI: 10.1227/NEU.0000000000001880_415
• Languages: English
• ISSNs: 0148-396X

Abstract

Abstract : INTRODUCTION: Dual-antiplatelet therapy (DAPT) is clinically indicated for patients undergoing endovascular procedures. Clopidogrel is the most commonly used P2Y12 inhibitor used for DAPT, and is a prodrug bioactivated by the CYP2C19 enzyme. Inferring platelet response can be done by genotyping CYP2C19 to determine metabolizer status. Patients with two functional alleles are considered normal metabolizers (NM), patients with one or two increased activity alleles are rapid (RM) or ultra-rapid metabolizers (UM), respectively, and patients with one or two loss-of-function (LOF) alleles are intermediate (IM) or poor metabolizers (PM), respectively. Another method of measuring antiplatelet response to clopidogrel is the VerifyNow Platelet assay (measured in platelet reactivity units [PRUs]), but the optimal range of PRUs in neuro-endovascular procedures has not yet been established. At UF Health, platelet reactivity testing is routine, but CYP2C19 genotyping is less frequent in patients undergoing these procedures. METHODS: Data were collected from the EMR patients who had a CYP2C19 genotype result ordered by the neurosurgical department. We assessed platelet reactivity tests and antiplatelet medication changes between different phenotype groups. Phenotypes included ultra-rapid, rapid, normal, intermediate and poor metabolizers. Patients were categorized as non-responders to clopidogrel if their platelet reactivity tests were >204 PRUs prior to medication change, hyper-responders if their platelet reactivity tests were <20 PRUs, and optimal responders if reactivity fell between 20-204 PRUs. RESULTS: 41 neurosurgical patients were genotyped. CYP2C19 phenotypes included ultra-rapid metabolizers (10%), rapid metabolizers (34%), normal metabolizers (37%), intermediate metabolizers (12%) and poor metabolizers (7%). Six patients had dose decreased to 75 mg QOD; 83% were hyper-responders. Three patients had their dose halved; 100% were hyper-responders. Four patients were switched to ticagrelor; 100% were clopidogrel non-responders. CONCLUSION: Patients who had their clopidogrel dose reduced were generally classified as hyper-responders based on platelet reactivity testing, and majority had increased CYP2C19 enzyme activity based on genotype. Of the non-responders who had a medication change to alternative P2Y12 therapy, majority had decreased CYP2C19 enzyme activity.