Circulation, Vol 90, 1522-1536, Copyright © 1994 by American Heart Association
J Lefkovits and EJ Topol
Currently used antithrombotics such as heparin have a number of potential
limitations that may be overcome by the new class of agents that directly
inhibit thrombin. These agents variously block the active catalytic and/or
the anion binding exosites of the thrombin molecule and are potent and
specific inhibitors of thrombin's many biological actions, as demonstrated
by in vitro and animal models of thrombosis. Preliminary data indicate that
the direct antithrombins are safe and efficacious in humans, and their use
in acute coronary syndromes and coronary angioplasty in place of heparin
has yielded promising early results. Phase III trials in these clinical
settings are currently under way. Newer antithrombotics that inhibit
thrombin generation and thrombin activity at various strategic points
within the coagulation cascade are also in the early stages of development.
ARTICLES
Direct thrombin inhibitors in cardiovascular medicine
Department of Cardiology, Cleveland Clinic Foundation, OH 44195.
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