EINSTEIN–Pulmonary Embolism (PE) Study - EINSTEIN–PE
The goal of the trial was to evaluate treatment of the oral direct factor Xa inhibitor, rivaroxaban, compared with standard therapy among patients with symptomatic pulmonary embolism (PE).
Rivaroxaban will reduce symptomatic recurrent venous thromboembolism.
- Patients with acute symptomatic PE with/without deep vein thrombosis
Number of enrollees:4,833
Duration of follow-up: approximately 9 months
Mean patient age: 58 years
Percentage female: 46%
- Treatment with low molecular weight heparin, unfractionated heparin, or fondaparinux for >48 hours or treatment with >1 dose of a vitamin K antagonist prior to randomization
- Performance of thrombectomy
- Placement of vena cava filter
- Use of fibrinolytic therapy
- Contraindication to any study medication
- Another indication for a vitamin K antagonist
- Renal insufficiency
- Significant liver disease
- Bacterial endocarditis
- Active bleeding or high risk for bleeding
- Systolic blood pressure >180 mm Hg
- Use of a cytochrome P-450 inhibitor
- Limited life expectancy
- Symptomatic recurrent venous thromboembolism, defined as fatal/nonfatal PE or deep vein thrombosis
- Major or clinically relevant nonmajor bleeding
Patients with symptomatic PE were randomized to rivaroxaban 15 mg twice daily for 3 weeks, then 20 mg daily (n = 2,420) versus usual care with enoxaparin 1 mg/kg twice daily, then a vitamin K antagonist with goal international normalized ratio (INR) 2-3 (n = 2,413).
Intended treatment duration of 3, 6, or 12 months was determined by the treating physician prior to randomization.
Low-dose aspirin <100 mg daily, clopidogrel 75 mg daily, or both were allowed; however, nonsteroidal anti-inflammatory drugs were discouraged.
Overall, 4,833 patients were randomized. The mean age was 58 years, and 46% were women. PE was unprovoked in 65%, due to recent surgery or trauma in 17%, immobilization in 16%, estrogen therapy in 9%, and active cancer in 5%. PE was extensive (multiple lobes) in 25% of patients. Intended treatment duration was 3 months in 5%, 6 months in 57%, and 12 months in 37%. The percentage of time that INR was in the therapeutic range was 63%. Mean study drug duration was 216 days.
The primary efficacy outcome, recurrent venous thromboembolism, occurred in 2.1% of the rivaroxaban group versus 1.8% of the usual care group (p for noninferiority = 0.003).
The primary safety outcome, major or clinically relevant nonmajor bleeding, occurred in 10.3% of the rivaroxaban group versus 11.4% of the usual care group (p = 0.23).
Major bleeding: 1.2% versus 2.2% (p = 0.003), respectively.
Net clinical benefit (venous thromboembolism plus major bleeding): 3.4% versus 4.0% (p = 0.28), major bleeding: 1.1% versus 2.2% (p = 0.003), respectively.
Among patients with acute symptomatic PE, the use of fixed-dose rivaroxaban was noninferior to usual care with enoxaparin/vitamin K antagonist in the prevention of recurrent venous thromboembolism. Bleeding was similar or slightly reduced with rivaroxaban. Rivaroxaban represents a simpler management approach to the treatment of acute PE.
The EINSTEIN–PE Investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;Mar 26:[Epub ahead of print].
Presented by Dr. Harry Buller at ACC.12 & ACC-i2 with TCT, Chicago, IL, March 24, 2012.
Keywords: Vitamin K, Neoplasms, Morpholines, Enoxaparin, Thiophenes, Pulmonary Embolism, Estrogens, Venous Thromboembolism, Venous Thrombosis, Factor Xa
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