Randomized COMparison of platelet inhibition with abciximab, tiRofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes: the COMPARE trial. Comparison Of Measurements of Platelet aggregation with Aggrastat, Reopro, and Eptifibatide.
BACKGROUND
The relative anti-aggregatory effects of currently prescribed platelet glycoprotein IIb/IIIa receptor antagonists during and after percutaneous coronary intervention for acute coronary syndromes have not been established.


RESULTS
We randomized 70 acute coronary syndrome patients undergoing percutaneous coronary intervention to receive abciximab, eptifibatide, or tirofiban at doses used in the Evaluation of Platelet IIb/IIIa Inhibitor for STENTing (EPISTENT), Platelet glycoprotein IIb/IIIa in Unstable angina Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet Receptor Inhibition in ischemic Syndrome Management in Patients Limited by Unstable Signs and symptoms (PRISM-PLUS)/Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trials, respectively. Platelet aggregation (PA) in response to 20 micro mol/L of adenosine diphosphate was measured with turbidimetric aggregometry in both D-phenylalanyl-L-prolyl-L-arginine chloromethylketone and citrate-anticoagulated blood early (15 and 30 minutes) and late (4, 12, and 18 to 24 hours) after drug initiation. At 15 and 30 minutes, PA was significantly less inhibited by the tirofiban-RESTORE regimen compared with abciximab (P=0.028) and eptifibatide regimens (P=0.0001). The abciximab regimen, however, showed increasingly varied anti-aggregatory effects during continued infusion for > or =4 hours. Citrate exaggerated ex vivo platelet inhibition after eptifibatide and tirofiban, but had the opposite effect on abciximab. Of all regimens evaluated, the eptifibatide regimen inhibited PA most consistently throughout both the early and late periods.


CONCLUSIONS
Currently recommended drug regimens to inhibit the platelet glycoprotein IIb/IIIa receptor have distinct pharmacodynamic profiles that might affect their relative efficacy in acute coronary syndromes and percutaneous coronary intervention.
Batchelor
Wayne B
WB
Tallahassee Heart and Vascular Institute, Tallahassee Memorial Healthcare, Tallahassee, Fla 32308, USA. batch002@earthlink.net
Tolleson
Thaddeus R
TR
Huang
Yao
Y
Larsen
Rhonda L
RL
Mantell
R Michael
RM
Dillard
Patricia
P
Davidian
Marie
M
Zhang
Daowen
D
Cantor
Warren J
WJ
Sketch
Michael H
MH
Ohman
E Magnus
EM
Zidar
James P
JP
Gretler
Daniel
D
DiBattiste
Peter M
PM
Tcheng
James E
JE
Califf
Robert M
RM
Harrington
Robert A
RA
D000077284:Abciximab; D000208:Acute Disease; D000368:Aged; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000789:Angina, Unstable / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D015906:Angioplasty, Balloon, Coronary; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D000925:Anticoagulants / Q000494:pharmacology; D019343:Citric Acid / Q000494:pharmacology; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000628:therapy; D000077542:Eptifibatide; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D010455:Peptides / Q000494:pharmacology* / Q000627:therapeutic use; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013577:Syndrome; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use
D000590:Amino Acid Chloromethyl Ketones; D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019343:Citric Acid; D014443:Tyrosine; D000077466:Tirofiban; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone; D000077542:Eptifibatide; D000077284:Abciximab