The Novel Antiplatelet Agent Revacept in Cardiovascular Medicine: The Promise of Efficacy Without Bleeding

Abstract

Percutaneous transluminal coronary angioplasty (PTCA) with or without vascular stenting is commonly used to treat coronary heart disease. However, restenosis occurs in 30-50% of patients undergoing simple balloon angioplasty and in 10-30% of patients who receive an intravascular stent. Collagen exposure at the vascular damage site leads to platelet adhesion and aggregation mainly via the activation of glycoprotein (GP) VI (a primary platelet collagen receptor), which contributes to the generation of thromboxane (TX) A 2 . It is produced from arachidonic acid by the activity of cyclooxygenase (COX)-1. TXA 2 is a potent mediator of platelet aggregation, vasoconstriction, and vascular smooth muscle cells (VSMC) proliferation and migration. In patients undergoing PTCA, an early increase of the systemic biosynthesis of TXA 2 occurs and is largely suppressed by low-dose Aspirin, a selective inhibitor of platelet COX-1. Thus, platelet activation and enhanced TXA 2 biosynthesis in response to vascular damage and collagen exposure is an early event which may contribute to restenosis. In this review, we report and discuss the evidence obtained in vivo and in vitro that the blockage of the interaction of platelet GPVI with injured vascular components, using novel antiplatelet agents such as Revacept, represents a safe strategy to mitigate vascular restenosis. Revacept, a dimeric fusion protein of the extracellular domain of GPVI and the human Fc-fragment, inhibits collagen-mediated platelet adhesion and subsequent aggregation at the site of vascular injury. Finally, the possible utility of this pharmacological approach in the prevention of tumor metastasis is discussed.

The Anti-Aggregative Potential of Resolvin E1 on Human Platelets

“…This leads to platelet activation and adhesion, which are necessary processes for clot formation and inhibition of bleeding in the damaged vessel [ 9 , 10 ]. GPVI is being investigated for new antiplatelet drugs due to the fact that treatment with GPVI inhibitors would not affect hemostasis and would not induce an increased risk of hemorrhagic complications with long-term antiplatelet therapy [ 9 , 11 ].…”