What is the lowest dose of aspirin for maximum suppression of in vivo thromboxane production after a transient ischemic attack or ischemic stroke?
BACKGROUND
There is still worldwide disagreement about the optimal lowest dose of aspirin to be used in patients after a transient ischemic attack (TIA) or nondisabling stroke. We measured the urinary 11-dehydro-thromboxane-B(2) (uTXB(2)) excretion to compare the degree of suppression of in vivo platelet activation by various low doses of aspirin.


METHODS
60 patients were randomly allocated to treatment with either 30, 50, 75 or 325 mg of aspirin. All patients received a 413-mg loading dose of carbasalate calcium (equivalent to 325 mg of aspirin) on day 0. The study population was stratified into a subgroup with acute ischemic stroke (AIS; n = 20; onset of symptoms <48 h) and a subgroup with a recent TIA or minor stroke (TIA/mS; n = 40) with onset of symptoms beyond 30 days, but less than a year previously. Urine samples were collected on day 0, 1, 5, 11 and 28 in patients with AIS, and on day 0, 11 and 28 in the patients with a TIA/mS.


RESULTS
On day 28, mean uTXB(2) levels were 241, 130, 217 and 187 pmol/mmol creatinine in the four treatment groups (ANOVA, p = 0.43). In the AIS subgroup, uTXB(2) remained suppressed on days 5 and 11 in all except the patients with the lowest dose (mean uTXB(2) on days 5 and 11: 475 and 392 pmol/mmol creatinine; log-transformed ANOVA, p = 0.05).


CONCLUSIONS
In patients with a TIA or nondisabling stroke, a daily dose of 30 mg of aspirin provides sufficient suppression of thromboxane synthesis. No indication of a dose-effect relationship was found. However, whether such a low dose adequately suppresses thromboxane synthesis in patients with acute stroke is uncertain.
Dippel
Diederik W J
DW
Departments of Neurology and Hematology, Erasmus Medical Center, Rotterdam, The Netherlands. d.dippel@erasmusmc.nl
Van Kooten
Fop
F
Leebeek
Frank W G
FW
van Vliet
Huub H D M
HH
Mehicevic
Ajnira
A
Li
Simon S C
SS
Koudstaal
Peter J
PJ
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D012307:Risk Factors; D020521:Stroke / Q000628:therapy*; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000652:urine; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D013929:Thromboxane B2; C049235:11-dehydro-thromboxane B2; D001241:Aspirin