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

Abstract

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.

• Authors: Annika Lundström, Håkan Wallén, Magnus von Arbin, Gun Jörneskog, Bruna Gigante, Karin Höeg Dembrower, Evaldas Laurencikas, Ann Charlotte Laska
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 24 Issue 10 Pg. 2348-57 (Oct 2015) ISSN: 1532-8511 [Electronic] United States
• PMID: 26303791 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Blood Glucose
• Platelet Aggregation Inhibitors
• Clopidogrel
• Ticlopidine

Topics

• Aged
• Blood Glucose
• Carotid Artery Diseases
• Cerebral Small Vessel Diseases (diagnosis, diagnostic imaging)
• Clopidogrel
• Cohort Studies
• Female
• Glomerular Filtration Rate
• Humans
• Ischemic Attack, Transient (drug therapy, metabolism)
• Male
• Middle Aged
• Neuroimaging
• Platelet Aggregation
• Platelet Aggregation Inhibitors (adverse effects)
• Radiography
• Statistics, Nonparametric
• Stroke (drug therapy, metabolism)
• Sweden
• Ticlopidine (adverse effects, analogs & derivatives)
• Ultrasonography