fundamental study has remained the standard of care for more than 50 years, and it is hard to imagine any other single clinical study having as durable terbinex an impact on clinical practice and contributing to the saving of more lives. Although warfarin and related oral vitamin K antagonists have been a mainstay of medicine for the treatment and prophylaxis of thrombosis, indeed being the only oral anticoagulants for more than 50 years, warfarin is the drug we all love to hate. As Ansell et al summarized it, are challenging to use in clinical practice for the following reasons: they have a narrow therapeutic window, they exhibit considerable variability in dose response among patients due to genetic and other factors, they are subject to interactions with drugs and diet, their laboratory control is difficult to standardize, and maintenance of a therapeutic level of anticoagulation requires a good understanding of the pharmacokinetics and pharmacodynamics of warfarin and good patient communication.
2 Therefore, there has been a concerted effort on the part of the hematology and cardiology communities and the pharmaceutical industry Nepafenac to develop a new generation of oral anticoagulants that may offer the same or improved efficacy and safety without the unique challenges of warfarin. We are now seeing the fruits of that labor. New agents have been a major source of excitement, with numerous studies published in the past 5 years on the 3 leading new oral direct anticoagulants: dabigatran, rivaroxaban, and apixaban. There are also several additional promising braf inhibitor drugs in earlier stages of clinical development.
In this review, we focus on dabigatran, rivaroxaban, and apixaban and discuss the clinical trial results and the application of these agents. Some initial words of caution. For all the difficulties with warfarin, Clofarabine 123318-82-1 virtually every aspect of the drug is well known, including its mechanism of action and metabolism, a universally available tool for monitoring its therapeutic level, and widely available, highly effective reversal agents.2 Vitamin K, fresh frozen plasma, prothrombin complex concentrate, or recombinant factor VIIa have all been well validated for warfarin reversal, depending on the urgency of the situation.2 And although warfarin certainly is associated with a serious risk of bleeding, it is quite rare for patients to develop other noncoagulation related toxicities.
For the new direct anticoagulants to be widely adapted, they will need to be not only noninferior language or superior to warfarin for coagulation related safety and efficacy, but also comparably safe regarding the other realms of possible side effects. This is best illustrated by the recent negative experience with ximelagatran, the first oral direct thrombin inhibitor that was widely studied in humans. Despite the fact that ximelagatran was noninferior to enoxaparin/warfarin for the treatment of deep venous thrombosis, a critical increase in liver function abnormalities was observed in some patents,3 resulting in its withdrawal from therapeutic development in 2006 by AstraZeneca.Three new direct oral anticoagulants either have been recently approved by the US Food and Drug Administration or are the later stages of clinical trials. These are summarized in the Table.