TRIP

Xarelto: two new indications for oral anticoagulant

MIMS News, 2012

The direct oral factor Xa inhibitor, rivaroxaban (Xarelto), has been approved for two new indications.
In addition to the prevention of venous thromboembolism (VTE) following hip or knee replacement, (rivaroxaban) is now licensed for:
prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) and one or more risk factors (including congestive heart failure, hypertension, ≥75 years of age, diabetes mellitus and prior stroke or transient ischaemic attack);
treatment of deep vein thrombosis (DVT) and prevention of recurrent DVT and pulmonary embolism (PE) following an acute DVT.
Rivaroxaban (20mg once daily) was compared with dose-adjusted (target INR 2.5, range 2.0–3.0) in the pivotal randomised double-blind (n=14,264).
The primary efficacy endpoint (a composite of stroke and systemic embolism) occurred in 188 patients taking rivaroxaban (1.7% per year) compared with 241 in the warfarin group (2.2% per year); hazard ratio (HR) 0.79 from the per-protocol analysis (95% CI, 0.66–0.96; p<0.001 for non-inferiority).
Patients with renal impairment (CrCl 30–49ml/min; n=2950) were given a lower dose of rivaroxaban (15mg once daily) and in a displayed a similar treatment effect to that found in the overall trial.
The open-label non-inferiority (n=3449) investigated rivaroxaban in the treatment of acute symptomatic DVT.
Patients were randomised to receive rivaroxaban 15mg twice daily for 3 weeks then 20mg once daily for 3, 6 or 12 months (n=1731), or subcutaneous plus warfarin or (n=1718).
Rivaroxaban was equally efficacious as the active control in reduction of recurrent VTE (36 events [2.1%] versus 51 events [3.0%], respectively; HR 0.68; 95% CI, 0.44–1.04; p<0.001 for non-inferiority).
The EINSTEIN-Extension trial (n=1197) investigated the efficacy of rivaroxaban (20mg once daily) against placebo in the prevention of VTE recurrence, following treatment for DVT or PE.