Summary
Aspirin is the most commonly used antiplatelet drug for prevention of ischaemic stroke.
In order to determine the prevalence and nature of aspirin failure, we studied 51
adults admitted with suspected ischaemic stroke and already prescribed daily aspirin.
Within 48 hours (h) of onset, blood and urine samples were collected to assess platelet
aggregation, activation and aspirin response by a range of methods. All tests were
then repeated on a second sample taken 24 h after witnessed administration of 75 mg
or 150 mg aspirin. At entry to the study, incomplete response to aspirin, measured
by arachidonic acid (AA)-stimulated platelet aggregation, was found in 43% of patients.
Following in-hospital aspirin administration, there was a significant decrease in
AA-aggregation (p=0.001) suggesting poor adherence to therapy prior to admission.
However, residual aggregation (10–15%) persisted in 11 subjects – suggesting alternative
causes. In incomplete responders on admission, platelet aggregation with adenosine
diphosphate (ADP) was significantly higher compared with responders (p<0.05) but there
were no significant differences in collagen aggregation, platelet fibrinogen binding
or P-selectin expression, plasma von Willebrand factor, fibrinogen, high-sensitivity
C-reactive protein, or the urinary metabolite, 11-dehydro-TxB2. Incomplete platelet
inhibition is common around the time of acute cerebrovascular ischaemic events in
patients prescribed aspirin. Up to 50% of these observations appear due to incomplete
adherence to aspirin therapy. Intervention studies are required to determine the clinical
relevance of measured platelet response to aspirin in terms of outcome, and the effectiveness
of improved pharmacotherapy for stroke prevention.
Keywords
Antiplatelet agents - aspirin resistance - platelet pharmacology - stroke prevention
