Pharmacodynamic profile of the direct thrombin antagonist bivalirudin given in combination with the glycoprotein IIb/IIIa antagonist eptifibatide.
BACKGROUND
Because of the adverse characteristics associated with heparin, direct antagonists of thrombin have been investigated as anticoagulants during percutaneous coronary interventions. However, the hematologic and clinical interactions between direct thrombin antagonists and inhibitors of platelet glycoprotein IIb-IIIa are incompletely explored.


METHODS
Forty-two patients who underwent elective percutaneous coronary intervention were randomized to receive a bivalirudin 1.0 mg/kg bolus followed by a 4-hour infusion at 2.5 mg/kg/h; a bivalirudin 0.75 mg/kg bolus followed by a 4-hour infusion at 1.75 mg/kg; or a heparin 60 U/kg bolus. All the patients also received eptifibatide, given as 2 sequential boluses of 180 microg/kg followed by a 2 microg/kg/min infusion for 18 to 24 hours, and aspirin.


RESULTS
After the bolus dose of the study drug, turbidimetric platelet aggregation in response to 5 micromol/L adenosine diphosphate increased in patients assigned to heparin but not those assigned to bivalirudin. After eptifibatide, platelet aggregation was eliminated in all 3 treatment groups. The effect of heparin and the effects of both bivalirudin regimens on the formation of thrombin antithrombin complexes and prothrombin fragment 1.2 were comparable. Neither agent affected the formation of platelet-monocyte complexes or expression of CD 63 lysosomal antigen. There were no major bleeding events, and a single non-Q-wave myocardial infarction (MI) occurred in a patient treated with bivalirudin.


CONCLUSIONS
These findings show the feasibility of combining the direct thrombin antagonist bivalirudin with a potent antagonist of platelet glycoprotein IIb-IIIa. Clinical trials are needed to assess the safety and efficacy of this combination.
Kleiman
Neal S
NS
Methodist DeBakey Heart Center, and Baylor College of Medicine, Houston, Tex, USA. nkleiman@bcm.tmc.edu
Klem
Jeffrey
J
Fernandes
Laura S
LS
Rubin
Howard
H
Challa
Sarma
S
Solomon
Stuart
S
Maresh
Kelly
K
Arora
Umesh
U
Klem
Elizabeth
E
Buergler
John
J
Mathew
Shiba
S
Browning
Adrianne
A
DeLao
Tim
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D005240:Feasibility Studies; D005260:Female; D006493:Heparin / Q000494:pharmacology*; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000494:pharmacology*
D000925:Anticoagulants; D000991:Antithrombins; D006629:Hirudins; D010446:Peptide Fragments; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins; D006493:Heparin; D000077542:Eptifibatide; C074619:bivalirudin