ORLANDO – The investigational oral anticoagulant rivaroxaban was not inferior to a combination of the low-molecular-weight heparin enoxaparin and a vitamin K antagonist for reducing risk of recurrent deep venous thromboembolism for up to 1 year, reported investigators with the EINSTEIN Acute DVT study.
In an open-label study, venous thromboembolism (VTE) or pulmonary embolism recurred in 2.1% of 1,731 patients randomized to rivaroxaban and in 3.0% of 1,718 patients randomized to enoxaparin (Lovenox) followed by either warfarin or acenocoumarol. The data were reported by Harry R. Büller, M.D., Ph.D., at the annual meeting of the American Society of Hematology and online in the New England Journal of Medicine (Dec. 4, 2010 [10.1056/NEJMoa1007903]).
Incidence of major bleeding or clinically relevant nonmajor bleeding was identical in the two groups, at 8.1%. Additionally, rivaroxaban, a factor Xa inhibitor in late-stage clinical development, was superior in efficacy to placebo in a randomized double-blind extension study in patients who had completed 6-12 months of thromboprophylaxis.
"This regimen of 15 mg [rivaroxaban] twice a day for the first 3 weeks followed by 20 mg for the remainder period provides clinicians and patients, I think, with an attractive and simple treatment option for venous thrombosis, not only in the acute phase, but also when prolonged treatment is indicated," Dr. Büller of the Academic Medical Center in Amsterdam, the Netherlands, said in a media briefing.
The EINSTEIN Acute-DVT trial compared oral rivaroxaban alone with enoxaparin followed by a vitamin K antagonist for prophylaxis of recurrent VTE or pulmonary embolism in 3,449 patients. Rivaroxaban was delivered orally 15 mg twice daily for 3 weeks, followed by 20 mg orally once daily for 3, 6, or 12 months. Duration of treatment was at the discretion of the treating physician at the time of randomization.
The EINSTEIN-extension study compared rivaroxaban with placebo in 1,197 patients who had completed 6-12 months of rivaroxaban in the EINSTEIN studies or 6-12 months of a vitamin K antagonist, either in the EINSTEIN studies or in routine care.
The primary efficacy end point for both studies was the incidence of recurrent VTE. The primary safety outcome for the acute DVT trial was major bleeding or clinically relevant minor bleeding. The major safety outcome in the extension trial was major bleeding.
In the acute trial, there were 36 VTE events in the rivaroxaban group, compared with 51 in the enoxaparin/vitamin K antagonist group (hazard ratio, 0.68; P less than .001). A total of 8.1% of patients in each group experienced a recurrent VTE.
In the continuation trial, there were 8 events among 602 patients (1.3%) treated with rivaroxaban, compared with 42 of 594 patients (7.1%) treated with the enoxaparin/vitamin K antagonist regimen (hazard ratio, 0.18; P less than .001). There were four nonfatal major bleeding events among patients treated with rivaroxaban, versus none in those who received placebo.
Both trials were sponsored by Bayer Schering Pharma and Ortho-McNeil.