title: Pathophysiologic, rather than laboratory-defined resistance drives aspirin failure in ischemic stroke.
abstract: BACKGROUND
  A significant proportion of ischemic strokes occur while using aspirin and therefore can be considered as clinical aspirin resistance. Apart from this clinical description, aspirin resistance can be defined by laboratory tests of in vitro platelet reactivity. The correlation between clinical and laboratory-defined resistance, however, is far from perfect, and the heterogenous nature of stroke pathophysiology might play a role in this discrepancy.
  
  
  METHODS
  The level of in vitro platelet inhibition by aspirin was prospectively evaluated using the VerifyNow Aspirin Assay (Accumetrics, San Diego, CA) in patients presenting with ischemic stroke while using aspirin (n = 78). Demographic and clinical features, including stroke etiology, were compared among patients with and without sufficient level of platelet inhibition and an additional set of patients suffering from stroke while not using aspirin (n = 257). Similar analyses were performed in a separate validation cohort.
  
  
  RESULTS
  Laboratory evidence of insufficient platelet inhibition was detected in 16 of 78 patients (21%) with clinical aspirin resistance. On the other hand, 30 patients (38%) had stroke etiologies well known to be inadequately responsive to aspirin therapy. Overall, laboratory-defined resistance by itself could be considered to be accountable for the ischemic event in only 15% of these patients. The corresponding figure was 9% in validation cohort. Patients with sufficient level of platelet inhibition were more likely to harbor an anticoagulant responsive etiology compared with aspirin naive patients (odds ratio, 2.0; P = .033).
  
  
  CONCLUSIONS
  Our findings highlight that laboratory aspirin resistance because of insufficient platelet inhibition is relatively uncommon, whereas pathophysiologic resistance, signifying the presence of etiologies that cannot be efficiently treated with aspirin treatment, is a major contributor of clinical resistance in ischemic stroke.
authors: Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors: Nergiz
authors: N
authors: Agayeva
authors: Department of Neurology, Faculty of Medicine, On Dokuz Mayis University, Samsun, Turkey.
authors: Levent
authors: L
authors: Gungor
authors: Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
authors: Mehmet Akif
authors: MA
authors: Topcuoglu
authors: Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. Electronic address: arsavaem@hotmail.com.
authors: Ethem Murat
authors: EM
authors: Arsava
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects*; D002545:Brain Ischemia / Q000209:etiology*; D015331:Cohort Studies; D004351:Drug Resistance; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D020521:Stroke / Q000150:complications / Q000188:drug therapy / Q000473:pathology
chemical_list: D010975:Platelet Aggregation Inhibitors; D001241:Aspirin
keywords: Antiplatelet agents; antiplatelet resistance; aspirin; ischemic stroke; stroke etiology