A multicenter, randomized, double-blind trial of thromboprophylaxis efficacy has found that patients hospitalized with acute medical illness were less likely to develop deep vein thrombosis or thromboembolism when treated with oral rivaroxaban (Xarelto, Janssen Pharmaceuticals/Bayer HealthCare) for 35 days than those who were treated with subcutaneous enoxaparin for 10 days and oral placebo for 35 days. However, the patients treated with rivaroxaban experienced more bleeding events. The MAGELLAN study was published online Feb. 7 in the New England Journal of Medicine.
Between December 2007 and July 2010, MAGELLAN (Multi-Center, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban with Enoxaparin) randomized 8,101 patients of at least 40 years of age from 556 sites in 52 countries. One group received 10 mg of rivaroxaban daily for 35 days and the other group received 40 mg enoxaparin daily for 10 days and placebo for 35 days. The two groups were well-matched in terms of baseline characteristics, acute medical conditions and risk factors for developing thromboembolism.
Alexander T. Cohen, MD, of the King’s College Hospital in London, and colleagues excluded patients for various reasons including never receiving the medication, violation of good clinical practice standards and lack of adequate assessment of venous thromboembolism. The final cohort included 3,232 patients who received rivaroxaban and 3,271 patients who received enoxaparin and placebo.
The principal safety outcome was clinically relevant bleeding. The primary efficacy outcomes were a composite of asymptomatic proximal deep vein thrombosis, symptomatic distal or proximal deep-vein thrombosis, symptomatic nonfatal pulmonary embolism, or death related to venous thromboembolism through the first 10 days (day 10 analysis). The same factors were analyzed from the first day through day 35 (day 35 analysis). The researchers prespecified the day 10 analysis as the non-inferiority analysis and the day 35 analysis as the superiority analysis.
The day 10 analysis showed that patients experienced primary outcome events at equal rates (2.7 percent of the rivaroxaban group and 2.7 percent of the enoxaparin group); rivaroxaban met the non-inferiority criterion. The day 35 analysis revealed that 4.4 percent of the rivaroxaban group had a primary outcome event compared with 5.7 percent of the group that received enoxaparin and placebo; rivaroxaban met the criterion for superiority.
During the first 10 days, 2.8 percent of the patients receiving rivaroxaban experienced a safety event, compared with 1.2 percent of the patients receiving enoxaparin. The day 35 analysis revealed that 4.1 percent of the rivaroxaban group experienced a safety event, compared with 1.7 percent of the group that received enoxaparin. Five rivaroxaban patients and one patient in the enoxaparin group experienced fatal bleeding.
“The results of the current study support those from other studies that showed the efficacy of extended thromboprophylaxis but also the increased risk of bleeding,” the authors wrote. They suggested that further study is needed to identify the factors that influence bleeding risk in acutely ill people.
The authors noted that the inclusion of asymptomatic proximal deep vein thrombosis, identified by ultrasonography, may be a limitation of the study because it may have resulted in the treatment of asymptomatic disease, and because a number of patients either did not receive ultrasound exams or their ultrasonograms could not be properly assessed. “The extent to which the lack of data for these patients may have influenced the findings of the trial is not clear,” they acknowledged.
The study was funded by Bayer HealthCare Pharmaceuticals and Janssen Research and Development.