A prospective study evaluating clopidogrel resistance among patients with ischemic cerebrovascular events across different ethnic groups in Israel.

Abstract

Introduction: Clopidogrel is commonly used for secondary prevention after ischemic cerebrovascular events, but substantial interindividual variability in pharmacodynamics response has been reported. Individuals demonstrating resistance to clopidogrel face a higher likelihood of recurrent ischemic events. This study evaluated clopidogrel responsiveness among Jewish and Arab patients treated within the same regional healthcare setting.

Methods: This prospective cohort included 102 patients with ischemic cerebrovascular events (acute ischemic stroke or transient ischemic attack) receiving clopidogrel for secondary prevention. Patients received either a loading dose (300 in 62 patients, 600 mg in 1 patient) followed by maintenance therapy or at least 7 days of 75 mg daily maintenance dosing (n = 39) prior to blood sampling. Platelet responsiveness was measured using the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay (PLT VASP/P2Y12, BioCytex, France). Patients were categorized according to VASP platelet reactivity index (PRI) as adequate responders (PRI <50%), intermediate responders (PRI 50%-69%), or patients with high residual platelet reactivity, operationally defined in this study as PRI ≥70%.

Results: The study included 102 enrolled patients, of whom 57 (55.9%) were Jewish and 45 (44.1%) were Arab. A valid VASP-PRI measurement was available for 101 patients (57 Jewish and 44 Arab); one Arab patient had no evaluable PRI measurement. Therefore, analyses of platelet reactivity were based on 101 patients The median PRI for all patients was 65.5 (49.1-80.3), with no statistically significant differences between Jewish and Arab (p = 0.251). Overall, 42.6% were classified as non-responders, 29.7% as partial responders, and only 27.7% demonstrated adequate platelet inhibition. Jewish patients were significantly older than Arab patients (p = 0.008), whereas Arab patients had a significantly higher BMI (p = 0.019). Other demographic and clinical features were similar across groups.

Conclusions: A high proportion of patients demonstrated elevated residual platelet reactivity according to the operational PRI threshold used in this study. No statistically significant ethnic difference in PRI was detected; however, the ethnic comparison was exploratory and the study was not powered to exclude modest between-group differences. Larger prospective studies incorporating CYP2C19 genotyping and longitudinal clinical outcomes are warranted.