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Abstracts from the British Society for Cardiovascular Research Spring Meeting 2009

Poster presentations

URINARY 11-DEHYDRO-THROMBOXANE B2 AS A MARKER OF THE ANTI-PLATELET EFFECTS OF CLOPIDOGREL OR ASPIRIN THERAPY IN HEALTHY MALE VOLUNTEERS

1P. C. J. Armstrong, 1A. A. Dhanji, 1A. T. Tucker, 2J. A. Mitchell, 1T. D. Warner. 1Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK, 2National Heart and Lung Institute, Imperial College London, London, UK

Background Activated platelets release large amounts of the cyclooxygenase-dependent product, thromboxane A2 (TxA2), and increased urinary levels of the TxA2 metabolite 11-dehydro-thromboxane B2 (Tx-M) appear positively associated with atherosclerotic disease. Anti-thrombotic doses of aspirin significantly lower these levels, and such measurements have been linked to risk determination of stroke, myocardial infarction and cardiovascular death. Consequently, Tx-M is considered a marker of both platelet activation and aspirin anti-platelet effectiveness. Clopidogrel is another important anti-platelet therapy, but no study has been conducted to determine its effects upon Tx-M levels.

Methods A small non-blinded trial of 16 healthy male volunteers assigned to seven days of standard anti-thrombotic aspirin (75 mg/day) or clopidogrel (75 mg/day) therapy. Blood and urine was collected before and on day 7 of treatment. Platelets were incubated with arachidonic acid (AA) (1 mM) to stimulate the acute production of TxA2 and serum TxB2 levels determined by radioimmunoassay. Urinary 11-dehydro-TxA2 metabolites were measured using a commercial ELISA.

Results Aspirin abolished AA-induced serum TxB2 production (n = 8, p⩽0.05) and caused a significant reduction in Tx-M levels (58±9%, n = 8, p⩽0.05). Clopidogrel inhibited AA-induced TxB2 production by 45±9% (n = 8, p⩽0.05) and urinary Tx-M levels by 59±11% (n = 8, p⩽0.05).

Conclusion Standard anti-thrombotic doses of clopidogrel and aspirin inhibit Tx-M to similar extents. This suggests that basal platelet activation and TxA2 production in vivo in healthy volunteers is associated with activation of ADP-dependent pathways. The strong effects of clopidogrel upon urinary Tx-M may also explain why addition of aspirin to clopidogrel is not always associated with increased anti-thrombotic …

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