• Cardiology Clinical Trials
• Thrombotic Disorders

Rivaroxaban, a direct, specific, competitive factor Xa inhibitor that inhibits thrombin generation, is an effective treatment for venous thromboembolism (VTE). The Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep–Vein Thrombosis or Pulmonary Embolism trial [EINSTEIN PE; Buller HR et al. N Engl J Med 2012] reported data that showed that rivaroxaban was noninferior to standard therapy but had a superior bleeding profile in patients with pulmonary embolism (PE). Results were presented by Harry Roger Buller, MD, Academic Medical Center, Amsterdam, The Netherlands.

This was a multicenter, randomized, open–label, assessor–blind, event–driven, noninferiority trial that comprised patients with acute symptomatic PE with or without deep–vein thrombosis (DVT). Patients (n=4832) were randomized to receive open–label oral rivaroxaban 15 mg twice daily for 3 weeks, then 20 mg once daily, versus subcutaneous enoxaparin (1 mg/kg) twice daily for 5 days plus a vitamin K antagonist (VKA; acenocoumarol or warfarin), initiated within 48 hours of randomization. Enoxaparin was discontinued when the patient's international normalized ratio (INR) was ≥2.0 for 2 consecutive days after at least 5 days of enoxaparin treatment. INR was measured at least once a month and the dose of the VKA was adjusted to maintain an INR of 2.0 to 3.0. The study treatment duration was 3, 6, or 12 months, and patients were followed for 30 days post–treatment. The primary efficacy outcome was first recurrent VTE (defined as fatal or nonfatal PE or DVT). The principal safety outcome was the first major or nonmajor clinically relevant bleeding.

In this population of patients with acute symptomatic PE with or without DVT, rivaroxaban was noninferior to enoxaparin, followed by VKA for efficacy (2.1% vs 1.8%; HR, 1.12; 95% CI, 0.75 to 1.68; p=0.003 for a noninferiority margin of 2.0). Significantly fewer patients who were randomized to rivaroxaban had major bleeding compared with those who were treated with enoxaparin/VKA (1.1% vs 2.2%; HR, 0.49; 95% CI, 0.31 to 0.79; p=0.003). Major or nonmajor clinically relevant bleeding occurred in 10.3% of the rivaroxaban– versus 11.4% of enoxaparin/VKA–treated patients (HR, 0.90; 95% CI, 0.76 to 1.07; p=0.23). Primary efficacy and safety outcomes were similar between the two treatments, irrespective of age, body weight, gender, kidney function, and cancer. There was no difference in liver toxicity.

The investigators concluded that oral rivaroxaban, 15 mg twice daily for 3 weeks, followed by 20 mg once daily, provides patients and clinicians with a simple, single–drug approach for the acute and continued treatment of both DVT and PE, with a potential improvement in the benefit/risk profile.

• © 2012 MD Conference Express®