CYP2C19 Genotype and Platelet Inhibition by Clopidogrel in a Multiethnic Hawaiʻi Population
Jan Aurelio1, Jessica Wilson1, Sean Choi1, Reannon Suzuki1, Joo Won Choi2, Stacy Brown3
1University of Hawaii, John A. Burns School of Medicine, 2Department of Neurosciences, UC San Diego School of Medicine, 3The Queen's Medical Center, Neuroscience Institute
Objective:

To identify frequency of CYP2C19 loss-of-function (LOF) alleles in a multiethnic stroke population in Hawaiʻi.

Background:

The American Heart Association’s 2024 scientific statement highlights a paucity of data from diverse populations in P2Y12 inhibitor studies. Most data demonstrating associations between CYP2C19 LOF alleles and reduced clopidogrel efficacy are from studies of East Asian and White populations. Our institutional practice at the only Comprehensive Stroke Center serving the diverse state of Hawaiʻi includes routine CYP2C19 genotyping and measurement of P2Y12 inhibition using the VerifyNow-P2Y12 assay in ischemic stroke (IS)/Transient Ischemic Attack (TIA) patients treated with clopidogrel.

Design/Methods:

We conducted a single-center, retrospective study of adult patients admitted for IS/TIA between January 2021 and June 2023. Participants who underwent CYP2C19 genotyping and platelet reactivity units (PRU) measurement were included. Descriptive statistics were applied to examine group differences in CYP2C19 LOF and PRU across race/ethnicities, including Native Hawaiians, Pacific Islanders (NHPI), and Filipinos. Comparisons were performed using Pearson’s chi-square tests.

Results:

Among 596 IS/TIA patients with CYP2C19 genotype and PRU data (43.5% female, mean age 69.1 [SD = 14.4]), 34.1% of patients identified as East Asian, 25% as White, 18.1% as NHPI, and 14.8% as Filipino. Significantly higher proportions of poor/intermediate clopidogrel metabolism based on CYP2C19 genotype were identified among East Asians (63.5%), NHPIs (59.3%), and Filipinos (59.1%), relative to Whites (27.5%);  p<0.001. The same racial/ethnic groups had higher trending percentages of subtherapeutic PRU (PRU >180), though differences were not significant.

Conclusions:

NHPIs and Filipinos, like East Asian populations, may be at higher risk for clopidogrel inefficacy due to higher prevalence of CYP2C19 LOF alleles. Further analyses are indicated to examine relationships between CYP2C19 LOF and clinical outcomes in this multiethnic population.

10.1212/WNL.0000000000216133
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