Oral, direct Factor Xa inhibitor rivaroxaban in patients with acute symptomatic deep vein thrombosis or pulmonary embolism (2012)


Treatment of acute symptomatic PE

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To compare rivaroxaban to standard anticoagulant therapy with enoxaparin and vitamin K antagonist (VKA) in the treatment of patients with acute symptomatic PE 

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Trial design

Randomized, open-label phase III non-inferiority study
Active treatment: rivaroxaban 15 mg p.o. twice daily for 3 weeks followed by rivaroxaban 20 mg once daily for 3, 6 or 12 months (n=2419)
Control treatment: enoxaparin 1.0 mg/kg s.c. twice daily for at least 5 days in combination with VKA; enoxaparin discontinued, if INR ≥2, VKA continued for 3, 6 or 12 months (n=2413)

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Primary efficacy endpoint: symptomatic recurrent VTE (defined as the composite of recurrent DVT or fatal or non-fatal PE)
Primary safety endpoint: composite of major and clinically relevant nonmajor bleeding
Secondary outcomes: major bleeding, all-cause mortality, vascular events (acute coronary syndrome, ischemic stroke, transient ischemic attack, or systemic embolism), and net clinical benefit (defined as the composite of the primary efficacy outcome and major bleeding)

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Trial participants

4832 patients with acute symptomatic PE with or without symptomatic DVT

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Efficacy outcome: 50 patients (2.1%) in the rivaroxaban group and 44 patients (1.8%) in the standard-therapy group experienced a symptomatic recurrent VTE (primary efficacy endpoint). The outcome of a net clinical benefit occurred in 83 patients (3.4%) treated with rivaroxaban and 96 patients (4.0%) in the standard-therapy group
Safety outcome: The primary safety endpoint, a first major and clinically relevant non-major bleeding episode, was observed in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group. Major bleeding occured in 1.1% and 2.2% of patients respectively

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Efficacy: The fixed dose regimen of rivaroxaban is at least as effective for the initial and long-term treatment of PE as the standard therapy with enoxaparin followed by a VKA
Safety: The bleeding rates were similar in the two study groups, with fewer major bleeding events in the rivaroxaban group

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The EINSTEIN-PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-1297

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Corresponding author

Harry R. Büller, MD, Department of Vascular Medicine, Academic Medical Center, F4-275, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands, h.r.buller@amc.uva.nl

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