Newer anticoagulants in 2009

Abstract

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.

How I treat anticoagulated patients undergoing an elective procedure or surgery

“…10,12 In patients with renal function that is normal (CrCl Ͼ 80 mL/min) or mildly impaired (CrCl, 50-80 mL/min) dabigatran has an elimination half-life of 14-17 hours, 53 which implies that in such patients the last dabigatran dose should be given 3 days before surgery (ie, skip 4 doses). This period of interruption corresponds to 4-5 dabigatran half-lives (48-60 hours) which, in turn, corresponds to a minimal For personal use only.…”

Ionic Liquid Matrix for Direct UV-MALDI-TOF-MS Analysis of Dermatan Sulfate and Chondroitin Sulfate Oligosaccharides

“…19 A heparin pentasaccharide Arixtra (Fonda-parinux Sodium) is a drug administered for prophylaxis of deep vein thrombosis in surgical patients. 20 Danaparoid, a mixture of low-molecular-weight dermatan sulfate, chondroitin sulfate, and heparan sulfate, is also used as the anticoagulant and does not have a side effect of heparin-induced thrombocytopenia. 21 In addition to their anticoagulant properties, GAGs mediate a number of cell signaling events through their interactions with proteins.…”

Non‐adherence to new oral anticoagulants: a reason for concern during long‐term anticoagulation?

“…In a RCT that randomized thromboprophylaxis to aspirin and warfarin to mitral valve disease [13], the 5-year rate of embolic events was 14% for aspirin and 20% with warfarin (P = 0.187), but medication adherence was significantly lower with warfarin (42%) compared with aspirin (73%; P < 0.001). Most embolic events in the warfarin group (n = 24) occurred in nonadherent patients whose International Normalized Ratio (INR) was < 2.0, but the rate of events in adherent patients whose INR was within the therapeutic range was three times lower than with aspirin.Although our clinical experience with the new oral anticoagulants (NOACs) has been brief [16,17], it has led to some concerns mainly related to the lack of an antidote in cases of major bleeding [17] and to the concern that patients may have difficulty in remembering to take their medication without the requirement of blood monitoring. Consequently, if NOACs are not taken regularly, these new agents may become much less effective.…”

“…Although our clinical experience with the new oral anticoagulants (NOACs) has been brief [16,17], it has led to some concerns mainly related to the lack of an antidote in cases of major bleeding [17] and to the concern that patients may have difficulty in remembering to take their medication without the requirement of blood monitoring. Consequently, if NOACs are not taken regularly, these new agents may become much less effective.…”