Warfarin Replacements: Good for Patients, Challenging for Laboratories

Warfarin's monopoly on oral anticoagulation therapy, as well as that of other vitamin K antagonists derived from coumarin, is over. Two new classes of drugs, oral direct thrombin inhibitors (DTI)2 and oral direct factor Xa inhibitors (DFXaI), are steadily obtaining regulatory approval for prevention of thromboembolic events in patients who have atrial fibrillation, undergo hip or knee replacement surgery, or require treatment of pulmonary emboli and deep vein thromboses. The results from an expanding list of large, well-conducted randomized clinical trials confirm the efficacy and safety of DTI and DFXaI drugs as noninferior or superior to standard prophylactic or therapeutic anticoagulation therapies (1). Presently, the US Food and Drug Administration (FDA) and regulatory agencies in other countries have approved one DTI (dabigatran etexilate, Pradaxa®) and two DFXaI (rivaroxaban, Xarelto®; apixaban, Eliquis®) for one or more indications, and clinical trials that were recently completed or are underway will likely bring more drugs in these two classes to market with approval for additional indications (2).