Biochemical and pharmacological differentiation of dabigatran, apixaban and rivaroxaban

Dabigatran (D), apixaban (A) and rivaroxaban (R) have been approved for various indications at specific dosages. This study was designed to compare the biochemical and pharmacologic profile of these drugs in a battery of standardized tests. Powdered forms of commercially available active D, A and R were dissolved at 250 ug/ml and diluted for various testing. Global anticoagulant assays, interactions with fibrinolytic agents, effect on thrombin anti-thrombin complex and prothrombin fragment F1.2 activation, thrombin generation studies using functional and immunologic methods, platelet aggregation, whole blood clotting studies and in vivo bleeding studies were carried out. In the global anticoagulant assays, D produced strong anticoagulant effects followed by R. A produced relatively weaker effects. In the thrombin generation assays D was a relatively weaker inhibitor in comparison to both A and R. None of these agents produced any inhibition of agonist induced aggregation except D which inhibited thrombin induced aggregation and activation responses in platelets. In the whole blood assays, each agent produced it's own profile. D was stronger than A and R. In the in vivo bleeding studies, D produced stronger effects in comparison to both A and R. The currently available new oral anticoagulant drugs exhibit distinct biochemical and pharmacologic profiles which may impact their safety and efficacy outcomes.