Evidence map›Paper›PMID 42723528›Full record

Observational studyPharmacotherapy2026

Association Between CYP2C19 Genotype and P2Y12 Reaction Units in Patients Receiving Clopidogrel After Acute Ischemic Stroke: A Prospective, Observational Study.

Rachael M Stone, Annie Smith, Sonya Gunter, Andrew T Weko, Carter Gottschalk, Cheyenne Lee, Allison Ramsey, Miah Perch Weatherspoon, Bradford B Worrall

Abstract readObservational Study
In one paragraph

Observational study in Pharmacotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Rachael M StoneDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.ORCID https://orcid.org/0000-0001-7751-4948
Annie SmithDepartment of Pharmacy, University of Virginia Health, Charlottesville, Virginia, USA.
Sonya GunterDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Andrew T WekoDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Carter GottschalkDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Cheyenne LeeDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Allison RamseyDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Miah Perch WeatherspoonDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.
Bradford B WorrallDepartment of Neurology, University of Virginia School of Medicine, Charlottesville, Virginia, USA.

Funding

ACCP Foundation
6 · The paper itself

Abstract

backgroundRecurrent 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.

objectiveTo investigate the viability of PRUs as a surrogate biomarker for clopidogrel resistance, we aimed to assess the association of PRUs with CYP2C19 genotype, which has been previously proven as predictive of clinical outcomes in patients receiving DAPT after AIS.

methodsWe conducted a prospective observational study of adults with non-cardioembolic minor AIS or high-risk TIA treated with 21 days of DAPT between December 2021 and May 2023. PRUs were measured ≥ 12 h after a clopidogrel loading dose. The primary outcome was the group difference in PRUs by CYP2C19 LOF carrier status. Secondary outcomes included associations between high platelet reactivity (PRU ≥ 208), CYP2C19 genotype, and 30-day stroke recurrence.

resultsOf the 35 patients included in the primary analysis, 17% were CYP2C19 LOF carriers. Mean PRUs were significantly higher in LOF carriers (265 vs. 161; p < 0.01), and high platelet reactivity was more frequent among carriers (83% vs. 21%; p < 0.01) compared with noncarriers, respectively. Twenty-seven patients completed 30-day follow-up; 26% reported recurrent stroke symptoms, but neither CYP2C19 LOF status nor high platelet reactivity was associated. Post hoc application of the ABCD-GENE score did not improve prediction of high platelet reactivity or clinical outcomes.

conclusionsPRUs 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. However, PRUs were not associated with short-term clinical outcomes.

Indexed as

ClopidogrelCytochrome P-450 CYP2C19Ischemic StrokePlatelet Aggregation InhibitorsReceptors, Purinergic P2Y12AgedAspirinDrug ResistanceDual Anti-Platelet TherapyFemaleGenotypeHumansIschemic Attack, TransientMaleMiddle AgedProspective StudiesAspirinClopidogrelCYP2C19 protein, humanCytochrome P-450 CYP2C19Platelet Aggregation InhibitorsReceptors, Purinergic P2Y12clopidogrelcytochrome P‐450 CYP2C19pharmacogeneticsstroke

Identifiers

PMID42723528
PMCPMC13563196

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.