Clopidogrel Resistance after Minor Ischemic Stroke or Transient Ischemic Attack is Associated with Radiological Cerebral Small-Vessel Disease

Background: The objective of this study was to compare nonresponders (NR) and responders (R) to clopidogrel with respect to presence of microvascular and macrovascular pathology in a cohort of patients with recent minor ischemic stroke (IS) or transient ischemic attack (TIA). Methods: Seventy-two patients treated with clopidogrel after IS or TIA were evaluated 1 month after onset. Platelet aggregation was measured by multiple electrode aggregometry (Multiplate). Nonresponse was defined according to recent consensus. The degree of cerebral small-vessel disease (cSVD) was evaluated on computed tomography scans of the brain using Fazekas scale for white matter changes. Carotid atherosclerosis was evaluated by ultrasound or computed tomography/magnetic resonance angiography. Results: Twenty-two percent of patients were NR. Moderate to extensive cSVD was more common for NR than R, 56% versus 25%, odds ratio 3.9 (1.2-12), P = .03. Correspondingly, 39% of patients with cSVD were NR versus 14% of patients with no or mild cSVD. No differences were found between NR and R in prevalence or severity of carotid atherosclerosis. NR had higher platelet aggregation response than R after stimulation with arachidonic acid or thrombin receptor-activating peptide, indicating a general platelet hyperreactivity. In a univariate analysis, hypertension, previous IS, glucose intolerance, pulse pressure above median, and presence of moderate to extensive cSVD were associated with the NR phenotype. Conclusions: Nonresponsiveness to clopidogrel after minor IS or TIA is associated with radiological cSVD but not with carotid atherosclerosis. Practice/implications: Measurement of platelet function is warranted in patients with cSVD. Larger studies on alternative or tailored antiplatelet treatment for these patients should be initiated.