Does clopidogrel increase the degree of platelet inhibition when a platelet glycoprotein IIb/IIIa inhibitor has been given? Insights from an optical platelet aggregometry study

Introduction: While the CURE trial demonstrated the benefits of clopidogrel in acute coronary syndromes, patients receiving glycoprotein IIb/IIIa antagonists were excluded. Given the frequent coadministration of these two medications, we sought to examine their interaction and their combined effect on platelet inhibition. Methods: Ten patients admitted to the hospital with stable or unstable angina underwent phlebotomy prior to, three hours and six hours after administration of a standard oral loading dose of clopidogrel. The samples were then treated in vitro with incremental concentrations of tirofiban (0, 10, 20, 40, 60, and 80 ng/mL), and optical platelet aggregometry was performed utilizing ADP and TRAP as agonists. We analyzed the combined effects of these agents using a mixed effects model with time and tirofiban concentration as fixed effects, and subject and timing of phlebotomy as random effects. Results: There was no evidence of additional inhibition of platelet aggregation due to clopidogrel regardless of the concentration of tirofiban or the study agonist (ADP 20 μM or iso-TRAP). Specifically, there was no difference in the tirofiban dose-response curves with either platelet agonist for any of the three time points (before, and three and six hours after, clopidogrel administration). Discussion: There is no evidence that the combination of clopidogrel and tirofiban achieves greater inhibition of platelet aggregation than tirofiban alone.