Recent advances in anticoagulant therapy for acute coronary syndromes.
BACKGROUND
Despite major advances in the treatment of acute coronary syndromes (ACS), ischemic heart disease is still the leading cause of death in the industrialized world. Although unfractionated heparin (UFH) has been the anticoagulant of choice in ACS treatments, both low-molecular-weight heparins and direct thrombin inhibitors are at least as effective as UFH in comparative clinical trials. UFH has been linked to a discontinuation rebound in thrombin generation, which is associated with greater ischemic end points than those with the direct thrombin inhibitor hirudin. Furthermore, UFH can increase platelet activation in ACS.


METHODS
This review summarizes the investigation of new molecular approaches to further improve clinical outcomes in ACS.


RESULTS
The more recently developed synthetic pentasaccharide Org31540/SR90107A provides potent antithrombotic activity through selective inhibition of Factor Xa by high-affinity binding to antithrombin III. Unlike UFH, the pentasaccharide does not bind platelet factor 4 and is not associated with platelet activation. New approaches to coronary thrombosis prevention/treatment that involve inhibition higher up the extrinsic coagulation pathway have been suggested. In view of its undesirable features, UFH may become obsolete with the advent of newer antithrombotic agents.


CONCLUSIONS
Applications for the pentasaccharide and other new anticoagulants await results from definitive, large-scale trials.
Topol
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Department of Cardiology, the Cleveland Clinic, Cleveland, OH 44195, USA. topole@ccf.org
D000925:Anticoagulants / Q000627:therapeutic use*; D000990:Antithrombin III / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006493:Heparin / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D024764:Hirudin Therapy; D006801:Humans; D009203:Myocardial Infarction / Q000517:prevention & control*; D009844:Oligosaccharides / Q000627:therapeutic use*; D013577:Syndrome
D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D009844:Oligosaccharides; C417062:SR 90107A-ORG 31540; D000990:Antithrombin III; D006493:Heparin