EINSTEIN-DVT (rivaroxaban versus VKA + parenteral )
EINSTEIN-PE (rivaroxaban versus VKA + parenteral agent)
Primary efficacy endpoint: noninferiority
Recurrent symptomatic VTE
2.1% versus 3.0%,
2.1% versus 1.8%,
HR = 0.68 (95% CI 0.44–1.04)
HR = 1.12 (95% CI 0.75–1.68)
# recurrent events that were any type of PE
25 versus 24
32 versus 27
Secondary efficacy endpoint:
All-cause mortality
2.2% versus 2.9%
2.4% versus 2.1%
HR = 0.67 (95% CI 0.44–1.02)
HR = 1.13 (95% CI 0.77–1.65)
Net clinical benefit
2.9% versus 4.2%
3.4% versus 4.0%
HR = 0.67 (95% CI 0.47–0.95)
HR = 0.85 (95% CI 0.63–1.14)
Primary safety outcome:
Major bleeding or clinically relevant nonmajor bleeding
8.1% versus 8.1%
10.3% versus 11.4%
HR = 0.97 (99% CI 0.76–1.22)
HR = 0.90 (95% CI 0.76–1.07)
Major bleeding∧
0.8% versus 1.2%
1.1% versus 2.2%
HR = 0.65 (95% CI 0.33–1.30)
HR = 0.49 (95% CI 0.31–0.79)
Clinically relevant nonmajor bleeding∧ ∧
7.36% versus 7.0%
9.5% versus 9.8%
(statistics NR)
(statistics NR)
Warfarin TTR
57.7%
62.7%
Study conclusion
Rivaroxaban is noninferior to warfarin. Rivaroxaban is not superior to warfarin.
Rivaroxaban is noninferior to warfarin. Rivaroxaban is not superior to warfarin
NR: not reported, TTR: time in therapeutic range. ∧Major bleeding as defined in EINSTEIN: Clinical overt bleeding, with associated fall in hemoglobin of at least 2.0 g per deciliter, the need for transfusion of 2 or more units of red blood cells, involving a critical site or was fatal. ∧ ∧Clinically relevant nonmajor bleeding as defined in EINSTEIN: overt bleeding that did not meet the criteria for major bleeding but was associated with medical intervention, unscheduled contact with a physician, interruption or discontinuation of a study drug or discomfort, or impairment of activities of daily life.
