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.
BACKGROUND
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 muM 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).


CONCLUSIONS
There is no evidence that the combination of clopidogrel and tirofiban achieves greater inhibition of platelet aggregation than tirofiban alone.
Talreja
Deepak
D
Division of Cardiovascular Diseases, Mayo Clinic, W16, 200 First Street SW, Rochester, MN 55905, USA.
Lubbe
Dieter
D
Orford
James L
JL
Lennon
Ryan
R
DiBattiste
Peter M
PM
Berger
Peter B
PB
D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000097:blood / Q000188:drug therapy; D000077144:Clopidogrel; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013988:Ticlopidine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077144:Clopidogrel; D000077466:Tirofiban; D013988:Ticlopidine