GP IIb/IIIa inhibitors

Two classes of drugs exist GP IIb/IIIa inhibitors that inhibit these platelet effects at the level of the glycoprotein (GP) IIb/IIIa receptor on the platelet surface membrane. The first group are the thienopyridines (clopidogrel and ticlopidine).

Current treatments for acute coronary syndromes including unstable angina and non-ST-elevation myocardial infarction now include agents aimed at inhibiting platelet activation, adhesion, and aggregation with fibrinogen cross-linking.

These GP IIb/IIIa inhibitors complex activation by inhibiting adenosine diphosphate (ADP) binding to the platelet receptor. These oral agents have a slower onset and longer-term treatment duration. The CURE, TARGET, CREDO, and STAIG trials have demonstrated a 21% to 46% improvement in primary cardiac end points attributed to the addition of a thienopyridine.

Significant benefits were demonstrated with the addition of clopidogrel to aspirin among patients undergoing percutaneous coronary interventions (PCI) (4.5 % versus 6.4% cardiovascular death, myocardial infarction, or urgent revascularization).

The second group of GP IIb/IIIa inhibitors are the direct GP IIb/IIIa antibodies or receptor antagonists (abciximab, tirofiban, and eptifibatide). These drugs inhibit the final pathway of platelet aggregation via fibrinogen cross-linking.

Abciximab is a monoclonal antibody with a high affinity for both activated and resting platelets, whereas eptifibatide and tirofiban are nonantibody receptor inhibitors with less affinity for resting platelets and much faster dissociation rates (shorter half-lives) than abciximab.

Meta-analysis of several large clinical trials (PRISM, PURSUIT, PARAGON, CAPTURE, and GUSTO-IV) has suggested only a modest 12% overall survival benefit attributable to the use of direct GP IIb/IIIa inhibitors when added to other therapeutics in acute coronary syndromes. Several subpopulations of high-risk patients, however, may have significantly improved outcome due to these agents.

These include patients receiving emergent percutaneous interventions (34% reduction in primary end points versus 7% without GP IIb/IIIa), patients with raised troponin levels (58% reduced mortality versus 5% increase), and diabetic patients, in whom the greatest increase in survival was demonstrated. Of interest to physicians is that women who receive GP IIb/IIIa inhibitors appear to have a 14% increase in combined end points as compared with men.

The American College of Cardiology and American Heart Association guidelines and the Seventh American College of Chest Physicians (ACCP) Consensus Conference on antithrombotic therapies suggest that the thienopyridines are as effective as aspirin alone and recommend clopidogrel as an alternative in patients with aspirin insensitivity because of its lower side effects.

It is preferable to delay giving clopidogrel to patients who may undergo coronary artery bypass graft surgery (CABG) because of excessive postoperative bleeding. GP IIb/IIIa inhibitors are of most benefit in patients undergoing or likely to undergo PCI and may be of little benefit in patients who do not receive PCI. Eptifibatide is used more often because it costs less and there is more experience with its dosing

Add Comment