Key result
Bivalirudin inhibited thrombin-induced platelet activation more effectively than unfractionated heparin alone (1% vs 54% PAC-1 binding; P<0.05) or with eptifibatide.
Why the study?
Does bivalirudin reduce thrombin-induced platelet activation more effectively than unfractionated heparin alone or with eptifibatide in blood from patients with symptomatic coronary artery disease?
Does bivalirudin reduce thrombin-induced platelet activation more effectively than unfractionated heparin alone or with eptifibatide in blood from patients with symptomatic coronary artery disease?
Absolute Event Rate: 1% vs 54%
p-value: p=<0.05
In an in vitro model using blood from patients with coronary artery disease, bivalirudin inhibited thrombin-induced platelet activation more effectively than unfractionated heparin alone or in combination with eptifibatide.
Does not support changing antithrombotic regimens; leaves open whether superior in vitro inhibition improves CAD outcomes.
OBJECTIVES: The effects of antithrombotic agents on the activation of platelets by thrombin were determined in blood from patients (n=12) with symptomatic coronary artery disease. METHODS: Blood obtained immediately before cardiac catheterization was incubated in vitro with therapeutic concentrations of unfractionated heparin (1.2 and 2.0 U/ml) alone and in combination with eptifibatide (unfractionated heparin 1.2 U/ml+eptifibatide, 1.7 microg/ml) or bivalirudin (8 and 14 microg/ml). An activated clotting time was determined. Platelet activation was induced with thrombin (0, 5, 15, and 40 U/ml) and assessed with the use of flow cytometry. Fibrin polymerization was prevented by the peptide Gly-Pro-Arg-Pro. The activation of glycoprotein IIb-IIIa and surface expression of P-selectin were identified with antibodies (PAC-1 and anti-CD62). RESULTS: The activated clotting time was 258+/-13 s with 1.2 U/ml unfractionated heparin alone, 396+/-8 s with unfractionated heparin+eptifibatide, and 348+/-9 s with 8 microg/ml bivalirudin. The binding of PAC-1 (reflecting the potential to aggregate) was decreased most effectively by bivalirudin (percentage of platelets binding PAC-1 in response to 15 U/ml thrombin-unfractionated heparin=54+/-7%, unfractionated heparin+eptifibatide=12+/-4%, bivalirudin=1+/-0.3% of platelets, P<0.05 for bivalirudin compared with unfractionated heparin or unfractionated heparin+eptifibatide and unfractionated heparin+eptifibatide compared with unfractionated heparin). Bivalirudin prevented thrombin-induced surface expression of P-selectin more effectively than unfractionated heparin alone or unfractionated heparin+eptifibatide (percentage of platelets expressing P-selectin in response to 15 U/ml thrombin-unfractionated heparin alone=74+/-5%, unfractionated heparin+eptifibatide=53+/-7%, bivalirudin=1+/-0.3%, P<0.05 for bivalirudin compared with unfractionated heparin or unfractionated heparin+eptifibatide). CONCLUSION: Comparison between pharmacologic concentrations shown to be therapeutic demonstrated that bivalirudin inhibited thrombin-induced activation of platelets to a greater extent than unfractionated heparin alone or in combination with eptifibatide.
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Schneider et al. (2006) studied symptomatic coronary artery disease (n=12). Bivalirudin vs. Unfractionated heparin alone or in combination with eptifibatide was evaluated on Binding of PAC-1 in response to 15 U/ml thrombin (p=<0.05). Bivalirudin inhibited thrombin-induced platelet activation more effectively than unfractionated heparin alone (1% vs 54% PAC-1 binding; P<0.05) or with eptifibatide.
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