TY - JOUR
T1 - Moving toward a more ideal anticoagulant
T2 - The oral direct thrombin and factor Xa inhibitors
AU - King, Christopher S.
AU - Holley, Aaron B.
AU - Moores, Lisa K.
PY - 2013/4
Y1 - 2013/4
N2 - Thromboembolic diseases are common. Heparins and the vitamin K antagonists have been the mainstay of therapy for >60 years, but both classes of agents have limitations. The "ideal" anticoagulant should be as effective and safe as heparin and vitamin K antagonists but should also be available in both a parenteral and an oral formulation, have predictable pharmacokinetics, and lack significant toxicities unrelated to the anticoagulant activity. Moreover, it should target a specific coagulation factor and have an antidote that leads to rapid reversal. There are now agents that fulfill some of these criteria. Here we review the pharmacology and effectiveness of the oral activated factor X inhibitors rivaroxaban and apixaban and the oral direct thrombin inhibitor dabigatran. These agents have undergone extensive phase 3 testing and are currently approved for various indications in the United States, Canada, or Europe. Rivaroxaban is approved in the United States for VTE prevention after major orthopedic surgery and for stroke prevention in atrial fibrillation and is approved in Europe and Canada for secondary prevention of VTE. Apixaban is currently under review by the US Food and Drug Administration for stroke prevention and is approved in Europe for VTE prevention following major orthopedic surgery. Dabigatran is approved in the United States for stroke prevention in nonvalvular atrial fibrillation and is being reviewed for secondary prevention of VTE.
AB - Thromboembolic diseases are common. Heparins and the vitamin K antagonists have been the mainstay of therapy for >60 years, but both classes of agents have limitations. The "ideal" anticoagulant should be as effective and safe as heparin and vitamin K antagonists but should also be available in both a parenteral and an oral formulation, have predictable pharmacokinetics, and lack significant toxicities unrelated to the anticoagulant activity. Moreover, it should target a specific coagulation factor and have an antidote that leads to rapid reversal. There are now agents that fulfill some of these criteria. Here we review the pharmacology and effectiveness of the oral activated factor X inhibitors rivaroxaban and apixaban and the oral direct thrombin inhibitor dabigatran. These agents have undergone extensive phase 3 testing and are currently approved for various indications in the United States, Canada, or Europe. Rivaroxaban is approved in the United States for VTE prevention after major orthopedic surgery and for stroke prevention in atrial fibrillation and is approved in Europe and Canada for secondary prevention of VTE. Apixaban is currently under review by the US Food and Drug Administration for stroke prevention and is approved in Europe for VTE prevention following major orthopedic surgery. Dabigatran is approved in the United States for stroke prevention in nonvalvular atrial fibrillation and is being reviewed for secondary prevention of VTE.
UR - http://www.scopus.com/inward/record.url?scp=84875977824&partnerID=8YFLogxK
U2 - 10.1378/chest.12-1362
DO - 10.1378/chest.12-1362
M3 - Article
AN - SCOPUS:84875977824
SN - 0012-3692
VL - 143
SP - 1106
EP - 1116
JO - Chest
JF - Chest
IS - 4
ER -