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Anticoagulants

VTE prevention: shortcomings of current anticoagulants lead to underuse

While current anticoagulant drugs have been the mainstay of antithrombotic therapy for decades, many clinicians find these medications challenging to use.17 These challenges, combined with underappreciation of the degree of venous thromboembolic (VTE) risk in certain patients, have led to considerable underuse of preventive antithrombotic therapy in some countries. Observational studies reveal that fewer than half of the patients at high risk of VTE receive thromboprophylactic treatment.57, 90, 91

The ideal anticoagulant

A new anticoagulant that more closely meets the criteria for an ideal anticoagulant could improve the quality of care. Such an advance also might help overcome gaps between evidence-based treatment recommendations and clinical practice. Researchers are exploring new anticoagulant targets in an effort to develop medications with the following properties89, 92:
  • Administered orally, one tablet once daily
  • Highly effective in reducing venous thromboembolism
  • Predictable dose response and kinetics
  • Low rate of bleeding events
  • No routine coagulation monitoring required
  • Wide therapeutic window
  • No dose adjustment required
  • Little interaction with food or other drugs
  • Low, nonspecific plasma protein binding
  • Inhibition of both free and clot-bound coagulation factors

Current anticoagulants

The most widely used medications for treating thrombosis are heparins and vitamin K antagonists (VKAs). These medications have proven efficacy, but lack many properties of an ideal anticoagulant.
  • Heparins require parenteral administration with its attendant drawbacks — inconvenience and discomfort
  • VKAs can be administered orally, but have a narrow therapeutic window and a slow onset of action, along with unpredictable pharmacology. In addition, many foods and drugs interact with VKAs. As a result, periodic blood tests and frequent dose adjustments are necessary to maintain the optimal degree of anticoagulation
  • Currently, long-term use of single coagulation factor inhibitors are limited by the requirement for parenteral administration17, 88
Vitamin K Antagonists >
  • 17 - Turpie AG. Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol. 2007;27(6):1238-1247.
  • 57 - Cohen AT, Tapson VF, Bergmann JF, et al; ENDORSE Investigators. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008;371(9610):387-394.
  • 90 - Spencer FA, Emery C, Lessard D, et al. The Worcester Venous Thromboembolism study: a population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med. 2006;21(7):722-727.
  • 91 - Geerts WH, Heit JA, Clagett GP, et al. Prevention of venous thromboembolism. Chest. 2001;119(1 suppl):132S-175S.
  • 89 - Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis. 2008;25(1):52-60.
  • 92 - Hirsh J, O'Donnell M, Weitz JI. New anticoagulants. Blood. 2005;105(2):453-463.
  • 88 - Spyropoulos AC. Investigational treatments of venous thromboembolism. Expert Opin Investig Drugs. 2007;16(4):431-440.
Venous thromboembolism
A condition in which a blood clot (thrombus) forms in a vein, which in some cases then breaks free and enters the circulation as an embolus, finally lodging in and completely obstructing a blood vessel, e.g., in lungs causing a PE. The term encompasses both DVT and PE.
Coagulation factors
Group of plasma protein substances (Factor I to XIII) contained in the plasma, which act together to bring about blood coagulation.
Coagulation monitoring
Coagulation monitoring is practice of checking a specific coagulation parameter in order to adjust the dose. A precise adjustment of the drug intake allows the patient to stay within a defined therapeutic range, which is measured by prothrombin time or International Normalized Ratio (INR).
Parenteral
Not through the alimentary canal but rather by injection through another route.
Vitamin K
An essential cofactor in the carboxylation of glutamic residues on the procoagulant forms of Factors II, VII, IX, and X. This ultimately leads to increased formation of thrombin and fibrin.

More about Anticoagulants

From the Image Library

Micrograph: deep vein thrombosis Positive duplex ultrasound showing the popliteal vein Positive duplex ultrasound showing a common femoral vein clot See all Venous Thrombosis

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Did You Know?

Hospitalised patients and residents of nursing homes account for about 60% of all cases of VTE.11

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