Ex vivo response to aspirin differs in stroke patients with single or recurrent events: a pilot study.
The dose of aspirin for secondary stroke prevention and the clinical meaning of ex vivo platelet abnormalities are debated. We assessed prospectively 39 noncardioembolic stroke patients in which 300 mg/day aspirin had proved effective (n=24) or ineffective (n=15) to prevent recurrent ischemic events. We evaluated platelet aggregation induced by arachidonic acid, adenosine diphosphate and epinephrine, and the sensitivity of platelets to increasing concentrations of the synthetic thromboxane mimetic U46619. Aggregation studies were repeated while subjects received 300 (study phase 1), and 600 (study phase 2) mg/day aspirin, respectively. Overall, arachidonic acid-induced platelet aggregation was less effectively inhibited during study phase 1 compared to phase 2. Arachidonic acid and epinephrine promoted a stronger platelet aggregation in aspirin nonresponders than in aspirin responders while taking 300 mg/day aspirin. On the other hand, 600 mg/day effectively inhibited platelet function in both clinical groups. A lower sensitivity to thromboxane receptors was also found during phase 1 of the study, although the response was similar between aspirin responders and nonresponders. This pilot study suggests that 300 mg/day aspirin is less effective than 600 mg/day to block the cyclooxygenase pathway in noncardioembolic stroke and, incomplete cyclooxygenase inhibition is associated with recurrent thromboembolic events despite adequate aspirin compliance. It is likely that patients could receive a more efficacious stroke prevention if the dose of aspirin is tailored to individual needs as reflected by laboratory findings.
Chamorro
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Neurology Service/IDIBAPS, Stroke Unit, Hospital Clínic, Villarroel 170, 08036, Barcelona, Spain. chamorro@medicina.ub.es
Escolar
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G
Revilla
M
M
Obach
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V
Vila
N
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Reverter
J C
JC
Ordinas
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D011446:Prospective Studies; D012008:Recurrence; D020521:Stroke / Q000188:drug therapy* / Q000503:physiopathology
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D001241:Aspirin