NEW DEVELOPMENTS IN ANTIPLATELET AND ANTITHROMBOTIC THERAPY

Several agents which inhibit platelet aggregation (aspirin, ticlopidin e, dipyridamole), and anticoagulants (vitamin K antagonists, unfractio nated heparin, low molecular weight heparins and heparinoids) are in c linical use. The search for more effective antiaggregating agents has resulted in the development of clopidogrel, a chemical analogue of tic lopidine with minimal bone-marrow suppressing effects, thromboxane syn thase inhibitors and receptor blockers, and antagonists of platelet re ceptor glycoproteins Ib and IIb/IIIa. In addition there is increasing therapeutic experience with chimeric monoclonal antibodies against the platelet receptors, glycoprotein IIb/IIIa, and to a minor extent, wit h synthetic peptides or non-peptide inhibitors against the same recept ors. Although new anticoagulants have become available their efficacy has only been tested in animal models of thrombosis: tissue factor pat hway inhibitor, factor Xa inhibitors (recombinant tick anticoagulant p eptide, antistasin, natural pentasaccharide and DX-9065), recombinant thrombomondulin and recombinant protein C have been tested in this man ner Considerable clinical progress has been made with direct thrombin inhibitors such as recombinant hirudin and hirulog which appear to be effective antithrombotic agents in patients. There is also clinical ex perience with argatroban, an arginine derivative which is a competitiv e antagonist to thrombin. However, PPACK, a tripeptide synthetic compo und which irreversibly blocks the active catalytic site of thrombin, h as not been investigated in the clinical setting.