The oral factor Xa inhibitor class shows promise for several indications requiring oral anticoagulant therapy. Rivaroxaban is the only oral factor Xa currently FDA approved in the U.S. and is approved for prevention of stroke in nonvalvular atrial fibrillation and venous thromboembolism (VTE) after major orthopedic surgery (hip or knee replacement).1 It has been found to be noninferior in the treatment of VTE compared to standard therapy with enoxaparin and oral vitamin K antagonists (VKA).2 Rivaroxaban and the oral factor Xa class offers many advantages over standard therapy for treatment of VTE and pulmonary embolism (PE), such as no regular dose adjustments, less monitoring, and avoiding injections.3,4 The investigators of the Einstein-PE study sought to determine the safety and efficacy of rivaroxaban in the initial and long-term treatment of PE when compared to traditional therapy of initial low molecular weight heparin (LMWH) and chronic oral VKA therapy.4
The Einstein-PE study was a multicenter, randomized, open-label trial of the efficacy and safety of rivaroxaban in patients with acute symptomatic PE compared to standard therapy of enoxaparin (1mg/kg twice daily) and an oral VKA (warfarin or acenocoumarol) for 3, 6 or 12 months as determined by the physician. Patients were enrolled if they had a confirmed acute symptomatic PE (with or without DVT). Exclusion criteria included a creatinine clearance 48>2.0 for two or more consecutive days. The oral VKA was adjusted to a therapeutic INR of 2.0-3.0. The primary efficacy and safety outcomes in the study were symptomatic recurrent VTE (fatal or non-fatal PE or VTE) and clinically relevant bleeding, respectively. Clinically relevant bleeding was the composite of major or clinically relevant nonmajor bleeding.4
The intention to treat analysis included 4,832 patients with similar baseline characteristics, including mean age of 57 years, weight 50-100kg for 83% of participants/group, and CrCl ≥ 80 mL/min for 64% of each group. Within the standard therapy group, median duration of enoxaparin therapy was 8 days and the percent of time INR was in therapeutic range was 62.7% (15.5% above 3.0 and 21.8% below 2.0). Adherence in the rivaroxaban group was greater than 80% for 94.2% of the participants. Actual occurrence of the primary efficacy outcome (recurrent VTE) occurred in 50 patients (2.1%) in the rivaroxaban group and 44 patients (1.8%) in the standard therapy group (p= 0.003 for noninferiority). There was no statistical difference between the groups for the primary safety outcome (first major or clinically relevant non-major bleed) with 274 (11.4%) events with standard therapy and 249 (10.3%) with rivaroxaban (p=0.23). More major bleeding occurred in the standard therapy group (2.2%) versus the rivaroxaban group (1.1%, p=0.003) with no difference in death between the groups. No difference was found in adverse events.4
The Einstein-PE trial demonstrated rivaroxaban to be as efficacious for treatment for symptomatic PE compared to standard therapy of enoxaparin and a VKA.4 Rivaroxaban offers advantages to current therapy with no injections, no monitoring and less drug-drug and ...