"Rivaroxaban versus Standard Therapy for Pulmonary Embolism Treatment". The New England Journal of Medicine. 2012. ClinicalTrials.gov number, NCT00439777.
Links to original sources: Wiki Journal Post Full Journal Article
Does rivaroxaban, an oral factor Xa inhibitor, offer a safe and effective single-drug approach to the treatment of pulmonary embolism compared to standard therapy with enoxaparin followed by vitamin K antagonist?
Rivaroxaban provides similar protection from recurrent venous thromboembolism as standard therapy and may have an improved benefit-risk profile, offering a simplified approach to the treatment of pulmonary embolism.
Standard therapy for pulmonary embolism typically involves a complex regimen of heparin followed by a vitamin K antagonist. Rivaroxaban, an oral direct inhibitor of factor Xa, has shown efficacy in preventing venous thromboembolism after major orthopedic surgery and in patients with atrial fibrillation. The EINSTEIN-PE study sought to test rivaroxaban as a single oral agent in the treatment of symptomatic pulmonary embolism.
As of the knowledge cutoff in 2023, there were no specific guidelines reflecting the results of this trial.
- Multicenter, randomized, open-label, event-driven, noninferiority trial - N=4,832 patients with acute symptomatic pulmonary embolism - Interventions: - Rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily) - Standard therapy (enoxaparin followed by adjusted-dose vitamin K antagonist) - Duration: 3, 6, or 12 months - Primary efficacy outcome: Symptomatic recurrent venous thromboembolism - Principal safety outcome: Major or clinically relevant nonmajor bleeding
- Inclusion criteria: Acute symptomatic pulmonary embolism with or without DVT - Exclusion criteria: Thrombectomy, vena cava filter placement, fibrinolytic agents for the current episode, treatment with more than 48 hours of anticoagulation before randomization, contraindications to enoxaparin, warfarin, or acenocoumarol - Baseline characteristics: Representative spectrum of patients presenting with symptomatic pulmonary embolism
- Rivaroxaban: 15 mg twice daily for 3 weeks, 20 mg once daily thereafter - Standard therapy: Enoxaparin with transition to warfarin or acenocoumarol; discontinuing enoxaparin once INR of 2.0 or higher was maintained for 2 consecutive days.
- Primary outcome: Recurrent venous thromboembolism occurred in 50 patients (2.1%) in the rivaroxaban group and 44 patients (1.8%) in the standard therapy group (hazard ratio, 1.12; 95% CI, 0.75 to 1.68). - Principal safety outcome: Clinically relevant bleeding occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07). - Major bleeding: Observed in 1.1% in the rivaroxaban group vs. 2.2% in the standard therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79). - Other outcomes: Acute coronary events and liver function abnormalities were low and similar between groups.
- Open-label design could introduce a diagnostic-suspicion bias. - Brief exposure to low-molecular-weight heparin prior to randomization may affect outcomes, although it is a part of current clinical practice.
The study was funded by Bayer HealthCare and Janssen Pharmaceuticals.
The complete study details and outcomes are available in The New England Journal of Medicine, 2012, and at the ClinicalTrials.gov database under the identifier NCT00439777.