The new anticoagulants.
Currently, the anticoagulants available are limited to warfarin, heparin compounds, and direct thrombin inhibitors. Warfarin, the most commonly used outpatient anticoagulant, has significant shortcomings. There are numerous drug/drug and drug/food interactions, and there is difficulty in dosing for one-third of patients. Numerous new anticoagulants are undergoing testing. The meta-pentasaccharides use the core molecule of heparin and replace one or more of the sulphated groups. They are administered by subcutaneous injection, but they require only once per week dosing. Numerous studies have shown equivalents or superiority to warfarin in treatment for thromboembolic events. Direct thrombin inhibitors block thrombin (IIa) and are used mostly for heparin-induced thrombosis or during coronary interventions. However, there is an orally administered direct thrombin inhibitor, Dabigatran, which is undergoing phase III testing. It can be given without regard to weight, age, or gender with minimal drug interactions. This drug has been proven to be equivalent to low molecular weight heparin (LMWH) in deep venous thrombosis (DVT) prophylaxis and showed no excess bleeding. Another promising group of anticoagulants with numerous investigations underway are the direct X inhibitors. Most are excreted renally as opposed to hepatic clearance with intravenous or oral dosing. Numerous phase II studies have shown them to have equivalent or superior prophylaxis for DVT when compared with LMWH. Oral IXa inhibitors and an oral thrombin cofactor inhibitor are also under development. It is clear that in the near future, anticoagulants will be available that offer significant advantages when compared to those currently in use.
Stone
William M
WM
Divisions of Vascular Surgery, Mayo Clinic Arizona, Scottsdale Arizona 85054, USA. Stone.William@mayo.edu
Tonnessen
Britt H
BH
Money
Samuel R
SR
D000925:Anticoagulants / Q000494:pharmacology* / Q000627:therapeutic use*; D000990:Antithrombin III / Q000494:pharmacology / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D000069604:Dabigatran; D006801:Humans; D009844:Oligosaccharides / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D013917:Thrombin / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000494:pharmacology / Q000627:therapeutic use
D000925:Anticoagulants; D001562:Benzimidazoles; D009844:Oligosaccharides; D011725:Pyridines; D014859:Warfarin; C479958:idraparinux; D000990:Antithrombin III; D013917:Thrombin; D000069604:Dabigatran