[Old and new oral anticoagulants. Pharmacological perspective]

Oral anticoagulant therapy is changing. In several clinical settings, warfarin and acenocumarol remain the standard oral anticoagulants. However, in view of the limitations of vitamin K antagonists, resulting from its slow onset of pharmacological action, its narrow therapeutic window, its variable metabolism, dependent of citochrome P450, its multiple pharmacological and food interactions and its potential risk for hemorrhagic complications, the last years have witnessed the emergence of new pharmacological groups in oral anticoagulant therapy, that can overcome these problems. At present, pharmacological investigation is focused in the development of new non-peptide molecules, which can inhibit essential moments of the coagulation system (thrombin and factor Xa), with a predictable and consistent pharmacodynamic and pharmacokinetic pattern, administered orally. Of these compounds, three of them (dabigatran, rivaroxaban and apixaban) already have defined (or to be defined) therapeutic indications, built on large interventional phase III studies, while many others are in less advanced development phases. This review summarizes and discusses the pharmacology of warfarin/acenocumarol and of the new direct thrombin and factor Xa inhibitors, exemplifying similarities and stressing differences that help us justify out therapeutic options.