lt;0.001 for non-inferiority; P=0.117 for superiority). Results for secondary endpoints as tested in hierarchical order in the ITT analysis are displayed in Table 3.
Among patients in the warfarin group, INR values were within the therapeutic range (2.0 to 3.0) a mean of 55% of the time (median, 58%; interquartile range, 43 to 71). The effect of rivaroxaban did not differ across the level of centre TTR (Time in Target INR Range of 2.0 - 3.0) in the equally sized quartiles (P=0.74 for interaction). Within the highest quartile according to centre, the hazard ratio with rivaroxaban versus warfarin was 0.74 (95% CI, 0.49 - 1.12).
The incidence rates for the principal safety outcome (major and non-major clinically relevant bleeding events) were similar for both treatment groups (see Table 4).
Table 3: Efficacy results from phase III ROCKET AF
Study population
ITT analyses of efficacy in patients with non-valvular atrial fibrillation
Treatment dosage
Xarelto 20 mg od (15 mg od in patients with moderate renal impairment)
Event rate (100 pt-yr)
Warfarin titrated to a target INR of 2.5 (therapeutic range 2.0 to 3.0)
Event rate (100 pt-yr)
Hazard ratio (95% CI)
p-value, test for superiority
Stroke and non-CNS systemic embolism
269
(2.12)
306
(2.42)
0.88
(0.74 - 1.03)
0.117
Stroke, non-CNS systemic embolism and vascular death
572
(4.51)
609
(4.81)
0.94
(0.84 - 1.05)
0.265
Stroke, non-CNS systemic embolism, vascular death and myocardial infarction
659
(5.24)
709
(5.65)
0.93
(0.83 - 1.03)
0.158
Stroke
253
(1.99)
281
(2.22)
0.90
(0.76 - 1.07)
0.221
Non-CNS systemic embolism
20
(0.16)
27
(0.21)
0.74
(0.42 - 1.32)
0.308
Myocardial infarction
130
(1.02)
142
(1.11)
0.91
(0.72 - 1.16)
0.464
Table 4: Safety results from phase III ROCKET AF
Study population
Patients with non-valvular atrial fibrillationa)
Treatment dosage
Xarelto 20 mg once a day (15 mg once a day in patients with moderate renal impairment)
Event rate (100 pt-yr)
Warfarin titrated to a target INR of 2.5 (therapeutic range 2.0 to 3.0)
Event rate (100 pt-yr)
Hazard ratio (95% CI)
p-value
Major and non-major clinically relevant bleeding events
1,475
(14.91)
1,449
(14.52)
1.03 (0.96 - 1.11)
0.442
Major bleeding events
395
(3.60)
386
(3.45)
1.04 (0.90 - 1.20)
0.576
Death due to bleeding*
27
(0.24)
55
(0.48)
0.50
(0.31 - 0.79)
0.003
Critical organ bleeding*
91
(0.82)
133
(1.18)
0.69 (0.53 - 0.91)
0.007
Intracranial haemorrhage*
55(0.49)
84
(0.74)
0.67 (0.47 - 0.93)
0.019
Haemoglobin drop*
305
(2.77)
254
(2.26)
1.22 (1.03 - 1.44)
0.019
Transfusion of 2 or more units of packe
