Rivaroxaban (Xarelto) Has Arrived
In July 2011, FDA approved a second novel oral anticoagulant drug, rivaroxaban (Xarelto, Janssen Pharmaceuticals Inc). Rivaroxaban is the first oral, rapid acting, highly selective direct inhibitor of factor Xa dosed once daily for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF) and prevention of deep vein thrombosis in the setting of knee or hip replacement surgery. Inhibition of factor Xa interrupts the intrinsic and extrinsic coagulation pathways, inhibiting both thrombin formation and development of thrombi, but it does not inhibit thrombin (activated factor II), and has no effects on platelets.
For the stroke indication, FDA advisors focused primarily on data from ROCKET AF (NEJM 2010) trial conducted in AF patients at high risk for stroke. The trial met its primary end point of demonstrating noninferiority to warfarin for the composite primary end point of stroke or non-central nervous system embolism (P <.001). Rivaroxaban proved superior to warfarin in an analysis that compared “as-treated” patients (P = .015), but not in the intention-to-treat analysis (P = .117). In a subgroup analysis looking specifically at secondary stroke prevention, rivaroxaban was associated with a 13% lower risk of recurrent stroke or systemic embolism compared with warfarin.
Selected Rivaroxaban Drug Facts
Use In Specific Populations
Apixaban (Eliquis) Coming Soon
A third new, novel, orally-dosed anticoagulant drug, apixaban (Eliquis, Bristol-Myers Squibb/Pfizer), is approved in Europe, but not the United States, for the prevention of venous thromboembolic events in patients who have undergone elective hip or knee replacement surgery. Recently released preliminary details from the ARISTOTLE trial suggest that apixaban was noninferior to warfarin in the AF/stroke setting for prevention of stroke and systemic embolism. The trial enrolled over 18,000 AF patients to either a twice daily dose of apixaban 5 mg twice daily or doseadjusted warfarin. Approval of apixaban in the United States is expected during Fall 2011. When approved, apixaban would compete with dabigatran and rivaroxaban.
Mr. Brown is professor emeritus of clinical pharmacy and a clinical pharmacist at Purdue University College of Pharmacy, Nursing, and Health Sciences, Department of Pharmacy Practice, West Lafayette, Indiana. This column’s information is based on current studies and references, but it may be changed without notice with newer studies or with different patient populations.