Comparison of the effects of pretreatment with tirofiban, clopidogrel or both on the inhibition of platelet aggregation and activation in patients with acute coronary syndromes.

OBJECTIVE: We sought to compare platelet inhibition produced by three antiplatelet regimens.

METHODS AND RESULTS: Sixty NSTE-ACS patients undergoing coronary angiography treated with aspirin and enoxaparin were randomised to receive tirofiban 0.4 microg/kg/min over 30 min plus 0.15 microg/kg/min over 24 h (A), clopidogrel 600 mg (B), clopidogrel 300 mg plus tirofiban (C); blood samples were taken at baseline and 2, 6 and 24 h after the drug administration, and were analyzed by light transmission aggregometry and flow cytometry. Treatment with clopidogrel 600 mg significantly reduced P-selectin expression in comparison with tirofiban alone at all time points (group B vs. A: P < 0.0001). However tirofiban inhibited platelet aggregation significantly more than clopidogrel 600 mg during the first 6 h (group A vs. B: P < 0.0001), and the addition of clopidogrel 300 mg did not inhibit platelet aggregation any more than tirofiban alone throughout the 24 h (group C vs. A: P = NS). All of the changes over time within each group were highly significant (P < 0.0001).

CONCLUSIONS: Tirofiban leads to greater early inhibition of platelet aggregation but less suppression of P-selectin expression than clopidogrel 600 mg. The addition of clopidogrel to tirofiban does not add any anti-aggregatory effect, but reduces P-selectin expression, thus likely adding a significant biological and clinical protective effect and providing a rationale for the combined use of the two drugs.