Combination antiplatelet therapy with aspirin and clopidogrel: the role of antecedent and concomitant doses of aspirin. An analysis of 711 patients.
BACKGROUND
Numerous randomized studies have shown that the combination of clopidogrel with aspirin yields better clinical outcomes than monotherapy in patients with acute vascular events. However, the impact of the aspirin dose on the antiplatelet potency of clopidogrel is unclear. We sought to compare the antiplatelet profile of aspirin 81 mg (n = 252) versus aspirin 325 mg (n = 459) before and during conventional clopidogrel loading (300 mg), and/or clopidogrel maintenance (75 mg/daily) therapy.


METHODS
Secondary post hoc analysis of an existing dataset consisting of 711 patients after coronary stenting (n = 601) and ischemic stroke (n = 110) treated previously with aspirin for at least 1 month, and then with aspirin + clopidogrel for at least 7 days was performed. Platelet assessments include conventional and whole blood aggregometry, rapid cartridge-based analyzers, and expression of platelet/endothelial cell adhesion molecule-1, P-selectin, and GPIIb/IIIa activity by flow cytometry measured before and after addition of clopidogrel.


RESULTS
There was a small but consistent yet non-significant trend towards more potent platelet inhibition with aspirin 325 mg compared to aspirin 81 mg for every platelet activation parameter before addition of clopidogrel. However, after loading and/or 1 week of chronic treatment with clopidogrel + aspirin, measured platelet parameters became very similar between the groups, and identical for collagen-induced aggregation and PFA-100 analyzer readings.


CONCLUSIONS
Before addition of clopidogrel, aspirin 325 mg has a tendency to provide stronger platelet inhibition than aspirin 81 mg. However, when clopidogrel and aspirin are used in combination, the higher aspirin dose does not translate into superior antiplatelet action. Given that the existing body of evidence supports the comparable efficacy and, particularly, superior safety of lower versus higher doses of aspirin, aspirin 81 mg should be the dose used in combination with clopidogrel.
Serebruany
Victor L
VL
HeartDrug Research Laboratories, Johns Hopkins University, Towson, MD 21204, USA. heartdrug@aol.com
Malinin
Alex I
AI
Atar
Dan
D
D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D015607:Stents; D020521:Stroke / Q000188:drug therapy; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin