New Approaches in Anticoagulation Therapy

Progress in the prevention and treatment of thromboembolic disease

The search for an ideal anticoagulant is motivated by the well-known shortcomings of currently available anticoagulants. Current therapies, such as heparins and vitamin K antagonists (VKAs), have a number of clinically relevant limitations contributing to underuse by clinicians worldwide.^{57, 89, 131}
{+}
Recently introduced anticoagulants target specific points in the coagulation cascade, unlike older therapies, which affect the activity of multiple clotting factors.^{95, 131}

Two newer oral anticoagulants, rivaroxaban and dabigatran etexilate, are currently approved in many countries. These agents are being prescribed for venous thromboembolism (VTE) prophylaxis in orthopaedic surgery. These novel oral medications have the potential to improve adherence with the anticoagulation regimen in the weeks following surgery. Also, the antiplatelet agent prasugrel, EMA-approved in patients with acute coronary syndrome (ACS) undergoing angioplasty, offers a new option to help prevent coronary reocclusion.²⁴⁵

One of the main goals of ongoing research is to develop medications with as many properties of an ideal anticoagulant as possible, including ^{89, 92}:

Administered orally, one tablet once daily
Highly effective antithrombotic action
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, non-specific plasma protein binding
Inhibition of both free and clot-bound coagulation factors

New anticoagulation targets

Novel compounds targeting a pivotal point in the coagulation cascade may significantly enhance venous thromboembolism (VTE) prevention.

Learn more about new anticoagulation targets.

New targets for platelet inhibition

Targeting new platelet membrane receptors may lead to more-effective antiplatelet therapy.

Learn more about new targets for platelet inhibition.

Article references

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.
89 - Haas S. New oral Xa and IIa inhibitors: updates on clinical trial results. J Thromb Thrombolysis. 2008;25(1):52-60.
131 - Ansell J. Factor Xa or thrombin: is factor Xa a better target? J Thromb Haemost. 2007;5(suppl 1):60-64.
95 - Mackman N. Triggers, targets and treatments for thrombosis. Nature. 2008;451(7181):914-918.
245 - National Institute for Health and Clinical Excellence. Final appraisal determination: Prasugrel for the treatment of acute coronary syndromes with percutaneous coronary intervention. London, England: National Clinical Guideline Centre; 2009.
92 - Hirsh J, O'Donnell M, Weitz JI. New anticoagulants. Blood. 2005;105(2):453-463.

Acute coronary syndrome: This is an umbrella term used to cover any group of clinical symptoms compatible with acute myocardial ischaemia (chest pain due to insufficient blood supply to the heart muscle that results from coronary artery disease). Acute coronary syndrome covers the spectrum of clinical conditions ranging from unstable angina to STEMI and NSTEMI.
Coagulation cascade: Series of reactions by which a small stimulus is amplified to produce rapid coagulation.
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).
Dabigatran: The active form of the prodrug dabigatran etexilate, an oral direct thrombin inhibitor.
Prophylaxis: The prevention of a disease or pathological condition.
Rivaroxaban: Oral, direct Factor Xa inhibitor.
Vitamin K antagonists: Vitamin K antagonists block the regeneration of the reduced form of vitamin K.
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.
Platelet: (Thrombocyte) Cell circulating in the blood that is involved in the cellular mechanisms of primary haemostasis leading to the formation of blood clots. When a blood vessel is injured, platelets gather at the site of injury and stick together to form a plug, thereby preventing blood loss.