Aspirin has stood the test of time over decades as the gold standard for relatively effective, safe, and inexpensive antiplatelet
therapy. However,
aspirin is only modestly effective in preventing arterial
thrombosis in certain settings, and it is virtually ineffective in others (for example, preventing
coronary restenosis after angioplasty). These observations have been the impetus for the development of more effective antiplatelet strategies, the rational basis of which is largely our understanding of normal platelet function. The most clinically effective
platelet inhibitors yet developed produce broad inhibition of platelet function by blockade of the final common pathway of aggregation, in which
fibrinogen binds to its platelet membrane receptor localized in the
glycoprotein (
Gp) IIb/ IIIa complex. The
Gp IIb/IIIa complex is a member of the family of
integrins, which are cell membrane receptors for adhesive
proteins. The binding of
fibrinogen to platelet
Gp IIb/IIIa occurs via a specific amino acid sequence,
arginine-glycine-aspartic acid. Effective antagonists of platelet
Gp IIb/IIIa function have included
monoclonal antibodies against
Gp IIb/IIIa,
peptide (
peptidomimetic) antagonists of
Gp IIb/IIIa, and nonpeptide (nonpeptide mimetic) antagonists of
Gp IIb/IIIa. The major risk of any antiplatelet strategy is the potential for
bleeding complications, since currently we do not understand the molecular distinction between protective hemostasis and pathologic
thrombosis.