The approval of two new indications for Xarelto^® (rivaroxaban) in 2011 offers major benefits for both physicians and patients by providing effective anticoagulation within 2-4 hours of the first oral dose, and simplifying drug administration by eliminating the need for dose adaptation and anticoagulation monitoring¹.

Xarelto^® is a selective, reversible direct inhibitor of Factor Xa, which reaches maximum plasma concentration from between 30 minutes to 3 hours post-dose. Xarelto^® is the only single-drug solution newly approved for the treatment of deep vein thrombosis (DVT) and secondary prevention of DVT and pulmonary embolism (PE) in

adults. Moreover, the pharmacological effect of Xarelto^® is assured. Unlike warfarin, the pharmacological action of Xarelto^® is not subject to the same genetic polymorphisms that can complicate warfarin treatment and result in sub-therapeutic anticoagulation. Rather, Xarelto^® dosing is not influenced by patient age, sex, and weight¹. Dose adaptation and anticoagulation monitoring are not required.

Xarelto^® has already shown superior efficacy to enoxaparin in the prevention of venous thromboembolism (VTE) in adult patients undergoing elective knee or hip replacement^2;3. Since receiving approval for this indication in September 2008,

Xarelto^® has essentially replaced other prophylactic strategies in many orthopaedic units and is now the most widely prescribed new oral anticoagulant, having been used in more than one million adult patients worldwide. The Xarelto^® phase III clinical trial program comprises three pivotal studies: EINSTEIN DVT, EINSTEIN PE, and the EINSTEIN Extension study which evaluates the benefit-risk ratio of long-term treatment. Einstein DVT and EXT have recently been published in the New England Journal of Medicine. As concluded by the authors Xarelto^® "...offers a simple, single-drug approach to the short-term and continued treatment of venous thrombosis that may improve the benefit-to-risk profile of anticoagulation."¹

In the treatment of acute symptomatic DVT (EINSTEIN DVT, an open-label, randomized, event-driven, non-inferiority study), Xarelto^® was compared with subcutaneous enoxaparin followed by a vitamin K antagonist¹. Both cohorts of patients with acute, symptomatic DVT were treated for 3, 6, or 12 months (n = 3449). The primary efficacy outcome (recurrent VTE) occurred in 2.1% of patients receiving Xarelto^® compared with 3.0% of patients receiving the comparator regimen (p < 0.001) - figure 1. The risk of bleeding was similar in both treatment groups.

In the prevention of recurrent VTE (EINSTEIN EXT), patients who had previously received treatment for DVT were randomized to receive Xarelto^® or placebo for an additional 6 to 12 months (n = 1196)¹. Comparing the long-term primary efficacy outcomes, Xarelto^® had clear superiority in the prevention.

of recurrence of VTE (1.3% versus 7.1%, respectively; p < 0.001) - figure 2. These results amount to an 82% reduction in the rate of recurrence in the Xarelto^® group, albeit with a small risk of major bleeding (0.7%), with no fatal haemorrhages. This is a notable outcome given the intentions of the study's authors: "The purpose of the Continued Treatment Study was to explore the benefit-to-risk ratio when treatment with [Xarelto^®] is administered after 6 to 12 months of anticoagulation. At this time point, clinicians must often balance the long-term risks of recurrent VTE if anticoagulation is stopped against the burden and risks of on-going therapy."