Off-target effects of glycoprotein IIb/IIIa receptor inhibitors

Abstract

Soon after identification of the platelet membrane glycoprotein (GP) IIb/IIIa, it has become a target of antiplatelet therapy. There are 3 intravenous GP IIb/IIIa receptor inhibitors, namely — eptifibatide, tirofiban and abciximab, used in the contemporary clinical practice, particularly in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). The aim of the current review is to summarize available knowledge concerning off-target effects of GP IIb/IIIa receptor inhibitors. All 3 drugs have similar antithrombotic properties, but differ with respect to pharmacodynamics, pharmacokinetics and off-target effects. Eptifibatide and tirofiban are highly specific GP IIb/IIIa receptor inhibitors, while abciximab is unselective and cross-reacts with integrin αυβ3 — a vitronectin receptor and leukocyte-associated integrin Mac-1. As a result of these interactions, abciximab seems to reduce the development of clinical restenosis, decrease infarct size, inhibit adhesion of monocytes to medical steel and modulate the inflammatory response. Intracoronary administration of abciximab provides higher drug concentration in the target area, increasing dose-dependent interactions with other integrins. Off-target effects of small molecule GP IIb/IIIa receptor inhibitors (i.e. eptifibatide and tirofiban) are predominantly connected with their suppressive influence on the inflammatory response. All in all, although GP IIb/IIIa receptor inhibitors are not recommended as a routine therapy during PCI, their antiplatelet properties and potential off-target effects may be beneficial in certain subsets of patients.