EINSTEIN-PE
Trial question
Is rivaroxaban noninferior to standard therapy for the treatment of symptomatic PE?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
47.0% female
53.0% male
N = 4832
4832 patients (2276 female, 2556 male)
Inclusion criteria: patients who had acute symptomatic PE with or without DVT
Key exclusion criteria: thrombectomy, vena cava filter placed, contraindication listed in the local labeling of enoxaparin, warfarin, or acenocoumarol, a CrCl < 30 mL/min, acute hepatitis, chronic active hepatitis, or cirrhosis, bacterial endocarditis, active bleeding or a high risk of bleeding
Interventions
N=2419 rivaroxaban (15 mg BID for 3 weeks, followed by 20 mg once daily)
N=2413 VKAs (enoxaparin followed by an adjusted-dose VKA)
Primary outcome
Symptomatic recurrent venous thromboembolism
2.1
1.8
2.1 %
1.6 %
1.1 %
0.5 %
0.0 %
Rivaroxaban
Vitamin K
antagonists
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in symptomatic recurrent VTE (2.1% vs. 1.8%; HR 1.12, 95% CI 0.75 to 1.68)
Secondary outcomes
No significant difference in net clinical benefit; VTE plus major bleeding (3.4% vs. 4%; HR 0.85, 95% CI 0.63 to 1.14)
Safety outcomes
No significant differences in major or clinically relevant nonmajor bleeding (10.3% vs. 11.4%, p=0.23; HR 0.90, 95% CI 0.76-1.07) and other adverse events.
Significant differences in major bleeding (1.1% vs. 2.2%, p = 0.003; HR 0.49, 95% CI 0.31-0.79).
Conclusion
In patients who had acute symptomatic PE with or without DVT, rivaroxaban was noninferior to VKAs with respect to symptomatic recurrent VTE.
Reference
EINSTEIN-PE Investigators, Buller HR, Prins MH et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97.
Open reference URL