February 8th, 2013

Xarelto Effective in Medically Ill Patients, But at High Bleeding Cost

The recent arrival of novel oral anticoagulants has provided important new options for treating and preventing venous thromboembolism (VTE). New indications for these drugs have been granted for patients with atrial fibrillation and for patients who have undergone orthopedic surgery. But an additional indication, for acutely ill medical patients at risk for VTE, does not appear likely in the near future, as a new trial published in the New England Journal of Medicine shows that one of these novel drugs, though effective at preventing VTE, also significantly increased bleeding risk.

In the Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban with Enoxaparin (MAGELLAN), first presented at the American College of Cardiology meeting in 2011, more than 8000 medically ill patients were randomized to subcutaneous enoxaparin for 10 days, followed by placebo for 25 days, or oral rivaroxaban (Xarelto, Johnson & Johnson) for 35 days.

In terms of efficacy, at 10 days rivaroxaban was found to be noninferior to enoxaparin; at 35 days it was found to be superior to enoxparin (for the first 10 days) and placebo:

  • By 10 days, the primary efficacy measure (a composite of asymptomatic proximal DVT, symptomatic DVT, symptomatic nonfatal PE, and VTE-related death) had occurred in 2.7% of patients in each group.
  • By 35 days, a primary outcome event had occurred in 4.4% of patients in the rivaroxaban group compared with 5.7% in the enoxaparin and placebo group (relative risk, 0.77; 95% CI, 0.62-0.96; P=0.02).

However, there were significantly more major or clinically relevant minor bleeding episodes in the rivaroxaban group at both day 10 and day 35:

  • At 10 days, clinically relevant bleeding occurred in 2.8% of rivaroxaban recipients versus 1.2% of enoxaparin recipients (RR, 2.3; P< 0.001).
  • At 35 days, clinically relevant bleeding occurred in 4.1% of patients in the rivaroxaban group versus 1.7%  of patients in the enoxaparin group (RR, 2.5; P<0.001).

Rivaroxaban is currently indicated in the U.S. for stroke reduction in patients with atrial fibrillation, for the treatment and prevention of recurrence of deep venous thrombosis and pulmonary embolism, and for DVT prophylaxis after orthopedic surgery. The FDA recently rejected an indication for the use of rivaroxaban in patients with acute coronary syndrome.

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