title: 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.
  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: Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. Electronic address: annika.lundstrom@ds.se.
authors: Annika
authors: A
authors: Lundström
authors: Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Håkan
authors: H
authors: Wallén
authors: Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Magnus
authors: M
authors: von Arbin
authors: Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Gun
authors: G
authors: Jörneskog
authors: Institute of Environmental Medicine, Unit of Cardiovascular Epidemiology, and Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Bruna
authors: B
authors: Gigante
authors: Division of Radiology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Karin
authors: K
authors: Höeg Dembrower
authors: Division of Radiology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Evaldas
authors: E
authors: Laurencikas
authors: Division of Internal Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
authors: Ann Charlotte
authors: AC
authors: Laska
mesh_terms: D000368:Aged; D001786:Blood Glucose; D002340:Carotid Artery Diseases; D059345:Cerebral Small Vessel Diseases / Q000175:diagnosis / Q000000981:diagnostic imaging*; D000077144:Clopidogrel; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D011859:Radiography; D018709:Statistics, Nonparametric; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism*; D013548:Sweden; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D014463:Ultrasonography
chemical_list: D001786:Blood Glucose; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Clopidogrel resistance; TIA; cerebral small-vessel disease; hypertension; ischemic stroke