New molecular entity: Rivaroxaban was FDA approved for prevention of deep vein thrombosis.
On July 1, 2011, FDA approved rivaroxaban oral tablets for the prevention of deep vein thrombosis (DVT) which may lead to pulmonary embolism (PE) in patients undergoing hip or knee replacement surgery. Rivaroxaban is an orally bioavailable factor Xa inhibitor that selectively blocks the active site of factor Xa. Activation of factor X via the intrinsic and extrinsic coagulation pathways plays an important role in blood coagulation.
Efficacy. Rivaroxaban's efficacy was established in 3 randomized, double-blind clinical studies enrolling more than 9,000 adults undergoing total hip or knee replacement surgery. In the first 2 studies (RECORD 1 and 2), patients undergoing elective hip replacement surgery were randomly assigned to receive 10 mg of rivaroxaban once daily starting 6 to 8 hours following wound closure or 40 mg enoxaparin once daily, starting 12 hours preoperatively. Rivaroxaban patients had a 71% and 76% (P<.001 for both) relative risk reduction in venous thromboembolism compared to those receiving enoxaparin. In the third study (RECORD 3), adults undergoing elective knee replacement surgery were randomly assigned to receive 10 mg of rivaroxaban 6 to 8 hours following wound closure or 40 mg enoxaparin 12 hours preoperatively. Rivaroxaban use resulted in a 48% risk reduction (P<.001) in VTE compared to enoxaparin.
Safety. In clinical trials, the most common adverse event (occurring in >5%) seen with rivaroxaban was bleeding, which could be serious or even fatal. In the 3 RECORD trials combined, 0.3% of patients developed a major bleed in the rivaroxaban groups compared to 0.2% in those receiving enoxaparin. Concomitant use of drugs affecting coagulation (eg, platelet aggregation inhibitors, other antithrombotic agents, fibrinolytic therapy, thienopyridines, and chronic use of non-steroidal anti-inflammatory drugs) can increase the risk of bleeding. As with other anticoagulants, epidural or spinal hematomas may occur in patients who are receiving neuraxial anesthesia or undergoing spinal puncture. Rivaroxaban is contraindicated in patients with active major bleeding.