Objective:

Background:

Clopidogrel (Plavix) is an antiplatelet medication that requires conversion to an active drug through metabolic pathways in the liver using the CYP2C19 enzyme.

Design/Methods:

This retrospective cohort study included 586 patients admitted to a comprehensive stroke center in the USA from 1/1/2022 – 1/1/2024 with a P2Y12 enzyme activity assay. Patients were excluded from the analysis if they were non-compliant on-treatment (n=3) or were clopidogrel naïve and did not receive timely in-hospital clopidogrel treatment prior to the assay (n=211). Platelet inhibition assay results were expressed as P2Y12 platelet reaction units (PRUs); >194 PRUs were poor metabolizers (HTPR), and <194 PRUs were adequate metabolizers. Chi-square tests were used to compare metabolizer status by principal diagnosis, demographics (age, sex, race, comorbidities), laboratory findings (A1C, CRP, ALT, AST), and AIS stroke subtype.

Results:

The analysis population included 372 (63%) patients; most patients (n=284, 76%) were chronic clopidogrel users while 88 patients received therapeutic clopidogrel in-hospital. The most common principal diagnoses were cerebral aneurysm (42%) and AIS (32%). HTPR was identified in 50 patients (13%). Compared to adequate metabolizers, poor metabolizers were more likely to be Hispanic (10% vs. 2%, p=0.01), to have diabetes (34% vs. 16%, p<0.001), to have elevated alanine transaminase (ALT; 39% vs. 17%, p=0.01), and were less likely to be on dual antiplatelet therapy (46% vs. 69%, p=0.01). Diabetes was significantly associated with HTPR independent of ethnicity. In the subset of patients with AIS (n=119), similar trends were identified.

Conclusions:

Providers should be aware that patients with diabetes and those of Hispanic ethnicity are at higher risk for HTPR. These findings support greater use of personalized medicine, especially when prescribing medications with known discrepant activity.