CURRENT STATUS AND FUTURE DIRECTIONS IN ANTIPLATELET THERAPY

Platelets are the principal effectors of cellular hemostasis and key mediators in the pathogenesis of thrombosis A variety of membrane receptors determine platelet reactivity with numerous agonists and adhesive proteins, and therefore represent key targets for the development of antiplatelet drug therapies In this regard, several rapid-onset and rapid-offset reversible ADP antagonists ore in clinical development, including reversible oral and rapid-acting intravenous P2Y(12) receptor antagonists Novel inhibitors of platelet adhesion in early development target vWF-GPIb/IX and collagen-GPVI interactions Since platelet aggregation also plays Such a critical role in the pathogenesis of arterial thrombosis, more patent agents that interfere with platelet aggregation via other pathways (e g, the thrombin receptor) ore also under clinical investigation However, the molar limitation to treatment with multiple antiplatelet agents is the increased bleeding risk associated with the enhanced antiplatelet effect, as exemplified by the clinical conundrum in patients with acute coronary syndrome who may need to undergo coronary artery bypass graft Surgery Aspirin and clopidogrel irreversibly inhibit platelet function, with the maximal antiplatelet effect occurring after 3-5 days These limitations might be solved with the availability of rapid-onset and rapid-offset ADP antogonists One issue that deserves further discussion is the duration of therapy There is conflicting evidence from the MATCH and CARESS trials as to the optimal duration of antiplatelet therapy In cerebrovoscular disease For coronary artery disease, the CHARISMA trial foiled to show the benefit of long-term clopidogrel in the overall trial population, although the 80% of patients with clinically evident atherothrombosis experienced a modest reduction in the primary endpoint, and emerging data with drug-eluting stents suggest that dual antiplatelet therapy may be required even beyond 1 year Clearly, additional studies are necessary to evaluate optimal antiplatelet therapy combinations and duration of therapies to permit maximal benefit with minimum harm in patients with cardiovascular disease This review provides detailed Information on the clinically most useful antiplatelet agents from aspirin to clopidogrel to GPIIb/IIIa antagonists and beyond, as well as several classes of novel antiplatelet drugs in development