Publshed in The Journal of the American Society of Anesthesiologists 2 2015, Vol.122, 236-237. doi:10.1097/ALN.0000000000000541
Authors: Charles Marc Samama, M.D., Ph.D., F.C.C.P.; Jerrold H. Levy, M.D., F.A.H.A., F.C.C.M.
THE non–vitamin K antagonist K oral anticoagulants (NOACs) represent a major step forward as compared with low-molecular-weight heparins and vitamin K antagonists. Four active molecules are now available on the market. Only one direct thrombin inhibitor (anti-IIa agent) has been developed: dabigatran (Pradaxa®) from Boehringer-Ingelheim (Biberach, Germany). Three anti-Xa agents are now marketed: rivaroxaban (Xarelto®) from Bayer (Leverkusen, Germany) and Johnson & Johnson (New Brunswick, NJ), apixaban (Eliquis®) from the alliance BMS (Princeton, NJ) and Pfizer (New York, NY), and edoxaban (Lixiana®) from Daiichi-Sankyo (Parsippany, NJ).
Although efficacy of NOACs administration was reported in different clinical trials, several issues deserve our attention. Both pharmacokinetics and pharmacodynamics for these agents are associated with significant intra- and interindividual variabilities and a huge number of drug interactions, and elimination is significantly affected by renal function, which could be associated with significant variations in plasmatic concentrations and an increased bleeding risk. Although new tests become more readily available for monitoring, which include the diluted thrombin time for dabigatran (Hemoclot®; Hyphen BioMed, Neuville sur-Oise, France), and specific anti-Xa assays for other direct Xa inhibitors, ranges that allow an optimal balance between effective anticoagulation and lower bleeding risk still need to be better defined for these agents. Finally, although clinical trials are underway, no specific antidotes are yet available and leave prothrombin complex concentrates (PCCs) as the principal therapeutic option. These hemostatic agents have been tested with conflicting results in different animal models and healthy volunteers, but efficacy has only been reported in a few bleeding cases.