Newer anticoagulants in 2009.
Several newer anticoagulants are under clinical development. Recently two of them, Dabigatran etexilate/Pradaxa. and Rivaroxaban/Xarelto obtained marketing authorization in Europe and Canada for the prevention of thromboembolic events following major orthopedic surgery such as total hip and knee replacement. The results of Phase III clinical studies in thromboprophylaxis in major orthopedic surgery are highlighted and discussed in detail. Ongoing Phase II and III clinical trials assess their efficacy in the secondary prevention and treatment of deep vein thrombosis and pulmonary embolism, and in the long-term prevention of stroke in patients with non-valvular atrial fibrillation and in combination with aspirin and clopidogrel in patients with acute coronary syndromes. Many other small antithrombotic molecules including a new generation of low molecular weight heparins, are currently in different stages of clinical development. In addition to being administered orally, the newer anticoagulant agents have a more balanced benefit/risk ratio and wider therapeutic window. They have a rapid onset of action, a predictable anticoagulant effect that does not require routine laboratory monitoring. They have minor food and drug interactions, including those with cytochrome P450 and P.gp. They are highly specific and targeted to a single coagulation factor, and could carry similar or less hemorrhagic risks compared to the older anticoagulant agents. Finally, they may be used in a broader variety of patients, especially the medically ill patients with advanced cancer, and the elderly without any dosage adjustment, regardless of the patient age, gender, body weight, or in patients with mild renal impairment. Their use in the general world will hopefully confirm the promising results of clinical trials.
Hotel Dieu University Hospital, 1, Place du Parvis Notre-Dame, 75181 Paris Cedex 04, France. mmsamama@aol.com
Meyer Michel
MM
Samama
Grigoris T
GT
Gerotziafas
D000284:Administration, Oral; D000925:Anticoagulants / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D065427:Factor Xa Inhibitors; D006801:Humans; D013917:Thrombin / Q000037:antagonists & inhibitors; D054556:Venous Thromboembolism / Q000188:drug therapy
D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D013917:Thrombin