Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients
What is the efficacy and safety of rivaroxaban administered for 35 days, as compared with enoxaparin administered for 10 days and followed by placebo, among hospitalized patients 40 years of age or older with reduced mobility and acute medical illness?
MAGELLAN (Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban With Enoxaparin) was a randomized, double-blind, active-comparator-controlled, multinational clinical trial (n = 8,101). The primary efficacy outcomes were the composite of asymptomatic proximal or symptomatic venous thromboembolism up to day 10 (noninferiority test) and up to day 35 (superiority test). The principal safety outcome was clinically relevant bleeding.
In the day 10 analysis, 78 of 2,938 patients (2.7%) in the rivaroxaban group and 82 of 2,993 patients (2.7%) in the enoxaparin group had a primary outcome event, with rivaroxaban meeting the prespecified criterion for noninferiority (relative risk [RR] with rivaroxaban, 0.97; 95% confidence interval [CI], 0.71-1.31; p = 0.003 for noninferiority). In the day 35 analysis, 131 of 2,967 patients (4.4%) in the group that received extended-duration rivaroxaban, as compared with 175 of 3,057 patients (5.7%) in the group that received enoxaparin followed by placebo, had a primary outcome event (RR with rivaroxaban, 0.77; 95% CI, 0.62-0.96; p = 0.02). Clinically relevant bleeding occurred in 111 of 3,997 patients (2.8%) in the rivaroxaban group and 49 of 4,001 patients (1.2%) in the enoxaparin group at day 10 (p < 0.001), and in 164 patients (4.1%) and 67 patients (1.7%) in the respective groups at day 35 (p < 0.001).
For the standard duration of thromboprophylaxis for hospitalized patients with acute medical illness, rivaroxaban was noninferior to enoxaparin. Rivaroxaban administered for an extended duration was superior to enoxaparin followed by placebo. Rivaroxaban was associated with an increased risk of clinically relevant bleeding both with standard and extended duration regimens.
This study demonstrates that while extended-duration rivaroxaban may be superior to enoxaparin, this is at the expense of an increased risk of clinically relevant bleeding. Ultimately and on balance, the prespecified analysis of net clinical benefit or harm did not show a benefit with rivaroxaban at either day 10 or day 35.
Keywords: Risk, Morpholines, Enoxaparin, Thiophenes, Venous Thromboembolism, Hemorrhage
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