NEW ORLEANS, LA—Rivaroxaban is non-inferior to enoxaparin in short-term use and superior in long-term use for the prevention of venous thromboembolism (VTE) in acutely ill medical patients, but demonstrates weaker safety outcomes, according to results of the MAGELLAN trial presented today at ACC.11, the American College of Cardiology’s 60th Annual Scientific Session.
The Phase 3, multinational MAGELLAN study evaluated the efficacy of oral rivaroxaban compared with subcutaneous enoxaparin for the prevention of VTE in 8,101 patients ≥40 years of age (median age 71 years) hospitalized for an acute medical condition (including acute heart failure, acute infectious disease, and acute respiratory insufficiency) plus a decreased level of mobility. Alexander T. Cohen, MD, MBBS, MSc, FRACP from King’s College Hospital, London, and colleagues evaluated the standard regimen of enoxaparin (10 days) in comparison to short-term (10 days) rivaroxaban. The study also looked at an extended treatment regimen of rivaroxaban (35 days) compared to enoxaparin (10 days) followed by placebo, as the optimal duration of VTE prophylaxis is unknown in this setting.
The study’s primary efficacy outcome was a composite of asymptomatic proximal DVT (detected by ultrasonography), symptomatic DVT, symptomatic non-fatal PE, and VTE-related death. The primary safety outcome was a composite of treatment-related major bleeding and clinically relevant non-major bleeding.
After a follow-up conducted at 10 days, the researchers found that the two drugs performed to the same level with regard to the primary efficacy outcome, with 2.7% of patients in both arms experiencing this endpoint (relative risk [RR] ratio=0.968, [0.713–1.334]; P=0.0025 for non-inferiority [one-sided]).
After a follow-up conducted at 35 days, rivaroxaban performed significantly better than enoxaparin followed by placebo, with 4.4% of modified intent-to-treat patients experiencing the primary efficacy outcome compared to 5.7%, respectively (HR=0.771, [0.618–0.962]; P=0.0211 for superiority [two-sided]. Absolute risk reduction was 1.3% and the relative risk reduction 22.9% with rivaroxaban therapy.
At Day 10, 1.2% of patients in the enoxaparin group experienced clinically relevant bleeding (major and non-major bleeding) compared with 2.8% of patients in the rivaroxaban group (RR=2.3; P< 0.0001). At 35 days, 1.7% of patients in the enoxaparin group experienced clinically relevant bleeding, compared to 4.1% of patients in the rivaroxaban group (RR=2.5; P<0.0001).
Dr. Cohen concluded today that a consistent net clinical benefit with rivaroxaban could not be established in the heterogeneous population studied. “As observed in previous studies in this area, we found an ongoing risk of VTE past the initial period of hospitalization or immobilization,” he said. “We did not see a consistently positive benefit-risk balance with rivaroxaban use, and thus further analysis is required to identify which groups of patients in MAGELLAN may derive benefit from thromboprophylaxis with rivaroxaban.”