Semin Vasc Med 2003; 03(2): 095-096
DOI: 10.1055/s-2003-40680

Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Antiplatelet and Anticoagulant Agents in Cardiovascular Disease: Basic Research and Clinical Applications

Karsten Schrör, Meinrad Gawaz
  • Institut für Pharmakologie und Klinische Pharmakologie, UniversitätsKlinikum Düsseldorf, Düsseldorf, Germany, and Medizinische Klinik und Poliklinik, Klinikum rechts der Isar and Deutsches Herzzentrum, Technische Universität München, Munich, Germany
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18. Juli 2003 (online)

During the last decade, a number of important findings have been made in cardiovascular pharmacology, many of them in the area of antiplatelet and anticoagulant drugs. For example, clopidogrel was introduced as the first alternative to aspirin as an oral antiplatelet drug. GPIIb/IIIa-antagonists, the first antiintegrin-type compounds, were developed and are now an established means for prevention of platelet aggregation at particular high-risk of acute platelet-dependent thrombus formation. In the field of anticoagulants, low-molecular heparins became the drugs of choice in the prevention of deep venous thrombosis, and fondaparinux, the first synthetic pentasaccharide, was introduced. Importantly, fondaparinux is the first heparin-type anticoagulant that is a pure factor Xa antagonist and is unable to bind thrombin. Clinical experience will show this concept's effectiveness. Subsequent to hirudin, and some synthetic analogs, a completely new class of anticoagulants, namely oral thrombin inhibitors-such as ximelagatran-have been developed. Ximelagatran is about to successfully pass a number of phase III-clinical trials and soon might enter the market. Finally, oral factor Xa inhibitors are in the pipelines of many drug companies and might change the prescriptions of anticoagulants considerably, possibly eliminating coumarin derivatives, the true dinosaurs in the field.

Fresh insights into the pathophysiology of vascular thrombosis come from the increasing appreciation of tissue factor as the initiating event of thrombus formation subsequent to vascular injury. This has also resulted in the design of new pharmacotherapeutic concepts, addressing the inhibition of tissue factor-dependent thrombus formation, for example, by inhibition of factor VIIa. Tissue factor release appears to be particularly relevant to plaque rupture in acute coronary syndromes. In addition, any local inhibition of tissue factor release, i.e. activation of the extrinsic pathway of coagulation including generation of factor Xa, might not result in a general prolongation of bleeding time, the most significant side-effect of many other antithrombotics and antiplatelet agents. Time will show whether these concepts work and any new findings will markedly improve our understanding of local thrombus formation and its pharmacological management.

The guest editors of Seminars in Vascular Medicine are most grateful to the many fine scientists who have made major contributions to this issue. The work, as a whole, may be considered state-of-the-art knowledge on antiplatelet and antithrombotic drugs and is written for educational purposes; for persons wishing a deeper insight into the current knowledge and further developments in the area. We hope the reader finds this information interesting and, in addition to the authors, would like to extend our thanks to the Editor in Chief of Seminars in Vascular Medicine, Jan Jacques Michiels, for providing us with the opportunity to publish these articles.