Antithrombotic drugs in vascular medicine: a historical perspective.
Many new antithrombotic and antiplatelet drugs have been developed that have markedly improved prophylaxis and treatment of thrombotic diseases. Clopidogrel, a potent new antiplatelet compound, is the first clinical alternative to aspirin for long-term oral treatment and prevention of arterial thrombosis. Another new, exciting category of antiplatelet compounds is the GPIIb/IIIa-antagonists, the first antiintegrins in clinical use and the most potent inhibitors of platelet aggregation. Low molecular weight heparins (LMWHs) are the quantitatively dominating group of new antithrombotics, which has replaced unfractionated heparin for the prophylaxis and treatment of venous thromboembolism. Current clinical evidence suggests that LMWHs might replace unfractionated heparin for the treatment and prophylaxis of atherothrombotic complications in acute coronary syndromes in the near future. Fondaparinux is the first synthetic pentasaccharide and a selective inhibitor of factor Xa with exciting clinical data; it could become an alternative LMWH for prophylaxis of arterial and venous thromboembolism in high-risk patients. The field of oral thrombin inhibitors is still dominated by the coumarins. However, much effort is being undertaken to develop new orally active drugs from which ximelagatran is currently the leading compound with a predicted better safety and efficacy profile. Alternatively, inhibitors of factor VIIa might be of interest as well. Open questions include, in particular, the possible individualization of drug therapy in dependence on the kind of disturbed platelet function or blood hypercoagulability, respectively.
Schrör
Karsten
K
Institut für Pharmakologie und Klinische Pharmakologie, UniversitätsKlinikum Düsseldorf, Düsseldorf, Germany.
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use; D001792:Blood Platelets / Q000502:physiology; D000077144:Clopidogrel; D004730:Endothelium, Vascular / Q000503:physiopathology; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D013927:Thrombosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin