3, 6 or 12 months

N=4,150
 Enoxaparin/VKAb)

3, 6 or 12 months

N=4,131
 
Symptomatic recurrent VTE*
 86

(2.1%)
 95

(2.3%)
 
Symptomatic recurrent PE
 43

(1.0%)
 38

(0.9%)
 
Symptomatic recurrent DVT
 32

(0.8%)
 45

(1.1%)
 
Symptomatic PE and DVT
 1

(<0.1%)
 2

(<0.1%)
 
Fatal PE/Death where PE cannot be ruled out
 15

(0.4%)
 13

(0.3%)
 
Major or clinically relevant non-major bleeding
 388

(9.4%)
 412

(10.0%)
 
Major bleeding events
 40

(1.0%)
 72

(1.7%)
 

a) Rivaroxaban 15 mg twice daily for 3 weeks followed by 20 mg once daily

b) Enoxaparin for at least 5 days, overlapped with and followed by VKA

* p < 0.0001 (non-inferiority to a prespecified hazard ratio of 1.75); hazard ratio: 0.886 (0.661 – 1.186)

The prespecified net clinical benefit (primary efficacy outcome plus major bleeding events) of the pooled analysis was reported with a hazard ratio of 0.771 ((95% CI: 0.614 – 0.967), nominal p value p= 0.0244).

In the Einstein Extension study (see Table 8) rivaroxaban was superior to placebo for the primary and secondary efficacy outcomes. For the primary safety outcome (major bleeding events) there was a non-significant numerically higher incidence rate for patients treated with rivaroxaban 20 mg once daily compared to placebo. The secondary safety outcome (major or clinically relevant non-major bleeding events) showed higher rates for patients treated with rivaroxaban 20 mg once daily compared to placebo.

Table 8: Efficacy and safety results from phase III Einstein Extension
 

Study population
 1,197 patients continued treatment and prevention of recurrent venous thromboembolism
 
Treatment dosage and duration
 Xareltoa)

6 or 12 months

N=602
 Placebo

6 or 12 months

N=594
 
Symptomatic recurrent VTE*
 8

(1.3%)
 42

(7.1%)
 
Symptomatic recurrent PE
 2

(0.3%)
 13

(2.2%)
 
Symptomatic recurrent DVT
 5

(0.8%)
 31

(5.2%)
 
Fatal PE/Death where PE cannot be ruled out
 1

(0.2%)
 1

(0.2%)
 
Major bleeding events
 4

(0.7%)
 0

(0.0%)
 
Clinically relevant non-major bleeding
 32

(5.4%)
 7

(1.2%)
 

a) Rivaroxaban 20 mg once daily

* p < 0.0001 (superiority), hazard ratio: 0.185 (0.087 - 0.393)

In addition to the phase III EINSTEIN program, a prospective, non-interventional, open-label cohort study (XALIA) with central outcome adjudication including recurrent VTE, major bleeding and death has been conducted. 5,142 patients with acute DVT were enrolled to investigate the long-term safety of rivaroxaban compared with standard-of-care anticoagulation therapy in clinical practice. Rates of majo