Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease.
OBJECTIVE
We investigated whether use of low-dose enteric-coated (EC) aspirin for secondary prevention of cardiovascular events has sufficient bioavailability to achieve complete platelet cyclooxygenase (COX) inhibition in all individuals.


BACKGROUND
Aspirin reduces cardiovascular morbidity and mortality in patients with pre-existing vascular disease; however, there is variability in the way individuals respond. Persistent normal platelet function despite therapy, referred to as "aspirin resistance," is associated with an increased risk of major cardiovascular events.


METHODS
We studied 131 stable cardiovascular patients between March and September 2002 who were taking 75 mg EC aspirin. Serum thromboxane (TX) B2 levels were assayed as a measure of COX activity. Mean arachidonic acid (AA)-induced platelet aggregation > or =20% was deemed evidence of persistent platelet activity and an incomplete aspirin response.


RESULTS
Patients of median age 63 years (61% men) were enrolled. Forty-four percent of patients had elevated serum TX B2 levels (>2.2 ng/ml). Arachidonic acid-induced platelet aggregation occurred more frequently in these patients (21% vs. 3%; p = 0.004). In all cases addition of exogenous aspirin during the assay abolished platelet aggregation. Patient weight and age were significant independent predictors of an incomplete response to EC aspirin (p = 0.025 and p < 0.001, respectively). These patients were also more likely to have a history of myocardial infarction (MI) (p = 0.038).


CONCLUSIONS
Many patients who are prescribed low-dose EC aspirin for secondary prevention of cardiovascular events have persistent uninhibited platelet COX activity. Younger and heavier patients and those with a previous MI are most likely to have an inadequate response to treatment.
Maree
Andrew O
AO
Department of Clinical Pharmacology, Royal College of Surgeons in Ireland, Dublin, Ireland.
Curtin
Ronan J
RJ
Dooley
Michelle
M
Conroy
Ronan M
RM
Crean
Peter
P
Cox
Dermot
D
Fitzgerald
Desmond J
DJ
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage* / Q000494:pharmacology; D001792:Blood Platelets / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008875:Middle Aged; D013608:Tablets, Enteric-Coated; D013929:Thromboxane B2 / Q000097:blood
D013608:Tablets, Enteric-Coated; D013929:Thromboxane B2; D001241:Aspirin