New oral anticoagulants in development

被引:88
作者
Weitz, Jeffrey I. [1 ,2 ,3 ]
机构
[1] Henderson Res Ctr, Hamilton, ON L8V 1C3, Canada
[2] McMaster Univ, Dept Med, Hamilton, ON, Canada
[3] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON, Canada
关键词
Anticoagulants; arterial thromboembolism; direct factor Xa inhibitors; direct thrombin inhibitors; venous thromboembolism; FACTOR-XA INHIBITOR; DEEP-VEIN THROMBOSIS; NONVALVULAR ATRIAL-FIBRILLATION; RIVAROXABAN BAY 59-7939; TOTAL KNEE REPLACEMENT; TOTAL HIP-REPLACEMENT; VENOUS THROMBOEMBOLISM; DABIGATRAN ETEXILATE; DOUBLE-BLIND; ANTITHROMBOTIC THERAPY;
D O I
10.1160/TH09-07-0434
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although currently available anticoagulants are effective for the prevention and treatment of thromboembolic disorders, they have several drawbacks. Low-molecular-weight heparins and fondaparinux produce a predictable level of anticoagulation that obviates the need for coagulation monitoring, but they must be given parenterally, which renders them inconvenient for long-term use. Vitamin K antagonists, such as warfarin, are administered orally, but produce a variable anticoagulant response because genetic polymorphisms, dietary vitamin K intake and multiple drug-drug interactions affect their metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. This is burdensome for patients and physicians, and costly for the healthcare system. These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa and can be given in fixed doses without coagulation monitoring. This paper focuses on the new oral anticoagulants in the most advanced stages of development.
引用
收藏
页码:62 / 70
页数:9
相关论文
共 80 条
[31]   Rivaroxaban for thromboprophylaxis after orthopedic surgery:: Pooled analysis of two studies [J].
Fisher, William D. ;
Eriksson, Bengt I. ;
Bauer, Kenneth A. ;
Borris, Lars ;
Dahl, Ola E. ;
Gent, Michael ;
Haas, Sylvia ;
Homering, Martin ;
Huisman, Menno V. ;
Kakkar, Ajay K. ;
Kalebo, Peter ;
Kwong, Louis M. ;
Misselwitz, Frank ;
Turpie, Alexander G. G. .
THROMBOSIS AND HAEMOSTASIS, 2007, 97 (06) :931-937
[32]   Comparison of ximelagatran with warfarin for the prevention of venous thromboembolism after total knee replacement [J].
Francis, CW ;
Berkowitz, SD ;
Comp, PC ;
Lieberman, JR ;
Ginsberg, JS ;
Paiement, G ;
Peters, GR ;
Roth, AW ;
McElhattan, J ;
Colwell, CW .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (18) :1703-1712
[33]   Physician compliance with guidelines for deep-vein thrombosis prevention in total hip and knee arthroplasty [J].
Friedman, Richard J. ;
Gallus, Alexander S. ;
Cushner, Fred D. ;
FitzGerald, Gordon ;
Anderson, Frederick A., Jr. .
CURRENT MEDICAL RESEARCH AND OPINION, 2008, 24 (01) :87-97
[34]   Towards a standardization of thrombin generation assessment: The influence of tissue factor, platelets and phospholipids concentration on the normal values of Thrombogram-Thrombinoscope assay [J].
Gerotziafas G.T. ;
Depasse F. ;
Busson J. ;
Leflem L. ;
Elalamy I. ;
Samama M.M. .
Thrombosis Journal, 3 (1)
[35]   Oral Thrombin Inhibitor Dabigatran Etexilate vs North American Enoxaparin Regimen for Prevention of Venous Thromboembolism After Knee Arthroplasty Surgery [J].
Ginsberg, Jeffrey S. ;
Davidson, Bruce L. ;
Comp, Philip C. ;
Francis, Charles W. ;
Friedman, Richard J. ;
Hue, Michael H. ;
Lieberman, Jay R. ;
Muntz, James E. ;
Raskob, Gary E. ;
Clements, Mary L. ;
Hentel, Stefan ;
Schnee, Janet M. ;
Caprini, Joseph A. .
JOURNAL OF ARTHROPLASTY, 2009, 24 (01) :1-9
[36]   Meta-analysis: Antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation [J].
Hart, Robert G. ;
Pearce, Lesly A. ;
Aguilar, Maria I. .
ANNALS OF INTERNAL MEDICINE, 2007, 146 (12) :857-867
[37]   Apixaban, an oral direct factor Xa inhibitor, inhibits human clot-bound factor Xa activity in vitro [J].
Jiang, Xiaosui ;
Crain, Earl J. ;
Luettgen, Joseph M. ;
Schumacher, William A. ;
Wong, Pancras C. .
THROMBOSIS AND HAEMOSTASIS, 2009, 101 (04) :780-782
[38]   Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial [J].
Kakkar, Ajay K. ;
Brenner, Benjamin ;
Dahl, Ola E. ;
Eriksson, Bengt I. ;
Mouret, Patrick ;
Muntz, Jim ;
Soglian, Andrea G. ;
Pap, Akos F. ;
Misselwitz, Frank ;
Haas, Sylvia .
LANCET, 2008, 372 (9632) :31-39
[39]   Antithrombotic therapy for venous thromboembolic disease [J].
Kearon, Clive ;
Kahn, Susan R. ;
Agnelli, Giancarlo ;
Goldhaber, Samuel ;
Raskob, Gary E. ;
Comerota, Anthony J. .
CHEST, 2008, 133 (06) :454S-545S
[40]   Safety, pharmacodynamics, and pharmacokinetics of single doses of BAY 59-7939, an oral, direct factor Xa inhibitor [J].
Kubitza, D ;
Becka, M ;
Voith, B ;
Zuehlsdorf, M ;
Wensing, G .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2005, 78 (04) :412-421