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

J Thromb Thrombolysis. 2009 Jan;27(1):36-43. doi: 10.1007/s11239-007-0174-x. Epub 2007 Nov 30.

Abstract

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Aged
  • Animals
  • Clopidogrel
  • Drug Administration Schedule
  • Drug Synergism
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • P-Selectin / analysis
  • Platelet Activation / drug effects*
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Platelet Function Tests / methods
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Ticlopidine / administration & dosage
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use
  • Tirofiban
  • Tyrosine / administration & dosage
  • Tyrosine / analogs & derivatives*
  • Tyrosine / pharmacology
  • Tyrosine / therapeutic use

Substances

  • P-Selectin
  • Platelet Aggregation Inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Tyrosine
  • Clopidogrel
  • Tirofiban
  • Ticlopidine