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

Abstract

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. 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%. 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. 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.