Association Between CYP2C19 Genotype and P2Y12 Reaction Units in Patients Receiving Clopidogrel After Acute Ischemic Stroke: A Prospective, Observational Study
PRUs appear to vary by CYP2C19 genotype in patients receiving DAPT after minor AIS or TIA, suggesting utility as a surrogate marker of clopidogrel nonresponse when genotyping is unavailable, and not associated with short‐term clinical outcomes.
Abstract
Recurrent stroke accounts for substantial morbidity and mortality worldwide, with up to 25% of ischemic strokes occurring in patients with prior strokes. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard for secondary prevention after minor acute ischemic stroke (AIS) or high‐risk transient ischemic attack (TIA). However, clopidogrel efficacy is reduced in carriers of cytochrome P450 2C19 (CYP2C19) loss‐of‐function (LOF) alleles. Although genotype‐guided DAPT has been shown to improve outcomes, the limited availability, high cost, and turnaround time of CYP2C19 genotyping constrain real‐world use. P2Y12 reaction units (PRUs) measured by the VerifyNow P2Y12 assay represent a potentially accessible alternative, but their relevance in the cerebrovascular population remains unclear.
Clopidogrel is first-line for secondary stroke prevention, but its effectiveness is affected by CYP2C19 genetic variation. An American Heart Association (AHA) scientific statement concluded that CYP2C19-guided P2Y12 inhibitor (P2Y12i) therapy is evidence-supported, though real-world application depends on implementatio...
D. M. Smith, Pamela Ramos Ramos, Shahrzad Ashena et al.· Clinical pharmacology and th...· 0 citations
Background Patient response to clopidogrel varies due to CYP2C19 genetic polymorphisms. Impaired metabolism has been linked to an increased risk of recurrent ischemic events. The purpose of this study was to examine CYP2C19 phenotypes and the impact on ADP aggregation in whole blood platelet aggregometry (WBPA) in pati...
Soumya Ravichandran, Cattien Phan, D. Meyer et al.· Clinical and applied thrombo...· 0 citations
BACKGROUND
Carriers of CYP2C19 loss-of-function alleles (LoFA) exhibit reduced metabolism of clopidogrel, potentially compromising the efficacy of dual antiplatelet therapy (DAPT) in acute ischemic stroke. We aimed to distinguish the impact of initial antiplatelet regimens from the discharge deescalation on functional...
Yu-Hsuan Wu, Chi-Sheng Wang, Kuo-Cheng Chang et al.· Journal of the American Hear...· 0 citations
The rationale and design of a genetic substudy aimed at clarifying the prognostic relevance of CYP2C19 genotype in AF patients undergoing PCI and informing the design of future genotype-guided antithrombotic trials are described.
S. Chiusolo, A. Verburg, C. Morizzo et al.· Bleeding Thrombosis and Vasc...· 0 citations
OBJECTIVE
Early neurological deterioration (END) is a common complication after acute ischemic stroke (AIS). Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is widely used in selected patients with minor ischemic stroke (MIS) to reduce early recurrent ischemic events. This study aimed to investigate the i...
Run-Hao Jiang, Li-Dong Ding, Jun Wang et al.· Neurological Research· 0 citations
Background.
The prevalence of clopidogrel resistance among patients with cardiovascular diseases (CVD) reaches 30–40 %, significantly increasing the risk of recurrent myocardial infarction (MI) and other thrombotic events. Genetic polymorphisms in CYP2C19 and ABCB1 account for up to 40 % of the variability in antipl...
K. S. Georgieva, S. Pavlova· Pharmacogenetics and Pharmac...· 0 citations
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