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(Circulation. 2007;116:552-560.)
© 2007 American Heart Association, Inc.

Contemporary Reviews in Cardiovascular Medicine

Beyond Unfractionated Heparin and Warfarin

Current and Future Advances

Jack Hirsh, MD; Martin O’Donnell, MB; John W. Eikelboom, MBBS

From the Henderson Research Centre, Hamilton Health Sciences Corporation (J.H.), Department of Medicine, McMaster University (J.H., M.O., J.W.E.), and Thrombosis Service, Hamilton General Hospital, Hamilton Health Sciences Corporation (J.W.E.), Hamilton, Ontario, Canada.

Correspondence to John W Eikelboom, Thrombosis Service, Hamilton General Hospital, Hamilton Health Sciences Corporation and McMaster University, Hamilton, Ontario L8L 2X2, Canada. E-mail eikelbj@mcmaster.ca

Key Words: anticoagulants • heparin • mortality • myocardial infarction • bivalirudin • enoxaparin • fondaparinux

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
Anticoagulants are widely used by cardiologists. Unfractionated heparin (UFH) and coumarins were discovered more than 60 years ago, and for more than 40 years, they have been the sole anticoagulant drugs available to clinicians.^1,2 Now, in 2007, several new anticoagulants have been introduced, and many more are under clinical development. Will these new anticoagulants replace the established drugs, and if so, how will these new anticoagulants fit into the therapeutic armamentarium of the practicing cardiologist?

Both UFH and coumarins were in clinical use long before their mechanism of action was completely understood. Both were also discovered by chance: UFH from extracts of dog liver and coumarins from extracts of vegetable matter (spoiled sweet clover). Low-molecular-weight heparin (LMWH) was also discovered by chance in the late 1970s and early 1980s and was in clinical use for at least a decade before its mechanistic advantages over UFH were identified.³ In the quest for new anticoagulants, scientists often turned to extracting natural anticoagulants from hemophagic animals and insects and from snake venoms.⁴ Defibrinating enzymes, factor Xa inhibitors, and thrombin inhibitors were isolated, purified, and in some cases synthesized by recombinant techniques. Of these anticoagulants, recombinant hirudin (from leeches) and recombinant NAPC2 (from hookworm) have been tested clinically. A few new anticoagulants (thrombomodulin, activated protein C) are synthesized by recombinant techniques, but with advances in structure-based design, most new anticoagulants are small molecules designed specifically to block the activity of coagulation enzymes either by fitting into their catalytic pockets, like a key into a . . . [Full Text of this Article]

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