title: The basis for aspirin dosage in stroke prevention.
abstract: Many strokes are thought to develop as a consequence of platelet aggregation on areas of arterial endothelial damage, with subsequent embolism or thrombus formation. Aspirin prevents platelet adhesion and aggregation by inhibiting the formation of thromboxane A2 by platelets. This suggests that aspirin could be used to prevent stroke. However aspirin also inhibits endothelial formation of the anti-aggregatory substance prostacyclin, though probably only in a slightly higher dose than that just capable of inhibiting platelet aggregation. Consequently, too high an aspirin dose may defeat its purpose. The effect of aspirin on platelets lasts for as long as they survive, whereas the effects of aspirin on endothelium are shorter. Theoretical considerations suggest that aspirin, given in brief pulses just to reach platelet inhibitory concentrations in plasma, and administered at the maximum interval that will maintain inhibition of platelet aggregation, should offer the most favourable balance between altered platelet and altered endothelial function from the viewpoint of stroke prevention. Data are presented showing that rapid rather than slow or delayed release aspirin preparations are necessary to achieve suitable plasma aspirin concentration-time profiles in humans, and that a peak plasma aspirin concentration of around 1.2 mg/L is necessary in vivo to inhibit aggregability of previously untreated platelets.
authors: Department of Medicine, University of Queensland, Brisbane.
authors: R A
authors: RA
authors: Brandon
authors: M J
authors: MJ
authors: Eadie
mesh_terms: D001241:Aspirin / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D002542:Intracranial Embolism and Thrombosis / Q000517:prevention & control; D002546:Ischemic Attack, Transient / Q000517:prevention & control
chemical_list: D001241:Aspirin