MAGELLAN Published: Rivaroxaban Reduces VTE Risk in Acutely Ill Patients

February 06, 2013

LONDON — The MAGELLAN trial, a study comparing the safety and effectiveness of the oral anticoagulant rivaroxaban (Xarelto, Bayer/Johnson & Johnson) against subcutaneous enoxaparin (Lovenox, Sanofi) in acutely ill patients, is now published in the February 7, 2013 issue of the New England Journal of Medicine [1].

First presented at the American College of Cardiology (ACC) 2011 Scientific Sessions by lead investigator Dr Alexander Cohen (King's College, London, UK) and reported by heartwire at that time, the study shows that rivaroxaban is noninferior to standard 10-day treatment with enoxaparin for the prevention of asymptomatic proximal or symptomatic venous thromboembolism (VTE) at day 10 and is superior to enoxaparin for the prevention of the same clinical events at day 35. For the superiority comparison, patients were treated with enoxaparin for 10 days followed by placebo to day 35.

There was a significantly increased risk of bleeding with rivaroxaban at day 10 and day 35, however. At day 10, the rate of clinically relevant bleeding was 2.8% in the rivaroxaban arm compared with 1.2% in the enoxaparin arm, a statistically significant difference. At day 35, the rate of clinically relevant bleeding was 4.1% in the rivaroxaban arm and 1.7% in the enoxaparin/placebo arm, a difference that was also statistically significant.

The primary efficacy and safety outcomes as reported at the 2011 ACC presentation in New Orleans, LA, are unchanged.

Patients With One or More Acute Medical Conditions

The MAGELLAN study randomized 8101 patients to 10 mg once daily of rivaroxaban for 35 days or the standard approved dose of enoxaparin (40 mg once daily by subcutaneous injection for 10 days). Patients included had one or more acute medical conditions, including infectious disease, heart failure, respiratory insufficiency, ischemic stroke, active cancer, or inflammatory/rheumatic diseases. The mean age of patients was 71 years, and approximately 20% had impaired renal function and 7% had active cancer (17% had a history of cancer).

The study's primary efficacy outcome was a composite of asymptomatic proximal deep vein thrombosis (DVT) (detected by ultrasonography), symptomatic DVT, symptomatic nonfatal pulmonary embolism (PE), and VTE-related death. The aim of the trial was to show noninferiority of rivaroxaban at 10 days and superiority at 35 days. This was achieved, with the primary outcome occurring in exactly the same percentage of patients in each group (2.7%) at day 10 and fewer patients in the rivaroxaban group at day 35 (4.4% vs 5.7%; p=0.02).

Rivaroxaban, a factor Xa inhibitor, is approved by the US Food and Drug Administration for the prevention of DVT in the setting of knee- and hip-replacement surgery. The indication for rivaroxaban in the orthopedic surgical setting is based on its performance in the three RECORD trials, in which it prevented VTE significantly better than enoxaparin with no increased bleeding risk. In November 2011, the FDA and European Commission each approved rivaroxaban for the treatment of patients with DVT and PE and for long-term treatment to prevent recurrence.

In addition, rivaroxaban was recently approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, but the FDA has declined to approve the drug for acute coronary syndromes, requesting missing data from the ATLAS ACS 2 TIMI 51 study. As a result, the company was issued a complete response letter and is working with the FDA to address the agency's questions.

The MAGELLAN study was funded by Bayer and Johnson & Johnson. Cohen reports serving on advisory boards for Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Pfizer, Portola, and Sanofi and receiving consulting fees, lecture fees, and payment for manuscript preparation and for the development of educational presentations from Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Johnson & Johnson, Mitsubishi Pharma, Pfizer, Portola, Sanofi, Schering Plough, and Takeda. Disclosures for the coauthors are listed in the paper.