Dual antiplatelet therapy unmasks distinct platelet reactivity in patients with coronary artery disease.
BACKGROUND
Platelet-induced thrombosis is a major risk factor for recurrent ischemic events, although platelet function in patients with cardiovascular disease taking aspirin and clopidogrel is very poorly characterized. The aim of this study was to assess platelet reactivity in patients with cardiovascular disease taking aspirin and clopidogrel.


METHODS
We developed a rapid assay to measure platelet aggregation in response to arachidonic acid, collagen, adenosine diphosphate (ADP), epinephrine and thrombin receptor activating peptide (TRAP) in 80 healthy volunteers. We then recruited 200 consecutive patients from outpatient clinics and the cardiac catheterization laboratory and tested platelet function. Platelet aggregation induced by epinephrine is a marker of global platelet reactivity. We tested platelet function in 146 patients compliant with antiplatelet therapy. Platelet aggregation to epinephrine was divided into quartiles. The platelet response to the other agonists was analysed based on the response to epinephrine.


RESULTS
Platelet reactivity increased significantly across the quartiles in response to epinephrine in healthy volunteers and patients (P < 0.0001). A significant increase in response across quartiles was seen with all agonists in healthy volunteers (P < 0.001). In contrast, a significant increase in response across quartiles was only seen with ADP in patients (P < 0.0001). Hypertension, smoking and diabetes were significantly associated with increasing platelet reactivity to epinephrine (P < 0.05).


CONCLUSIONS
This study shows that platelet response differs between healthy volunteers and patients on dual antiplatelet therapy. In patients with cardiovascular disease, dual antiplatelet therapy unmasks a distinct type of platelet reactivity in response to epinephrine and ADP but not other agonists.
Peace
A J
AJ
Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland. apeace@rcsi.ie
Tedesco
A F
AF
Foley
D P
DP
Dicker
P
P
Berndt
M C
MC
Kenny
D
D
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology*; D016022:Case-Control Studies; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood* / Q000188:drug therapy; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010979:Platelet Function Tests; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin; D004837:Epinephrine