ROCKET AF study design1,2
STUDY DESIGN
- Randomized
- Phase 3
- Multicenter
- Event-driven
- Active-controlled
- Phase 3
- Double-dummy
- Randomized
- Double-blind
- Multicenter
- Event-driven
- Active-controlled
- Phase 3
- Double-dummy
EFFICACY ENDPOINT
The primary efficacy endpoint was composite of stroke (ischemic or hemorrhagic) and SE.
SAFETY ENDPOINT
The principal safety endpoint was a combination of major bleeding and clinically relevant nonmajor bleeding events.
XARELTO® 20 mg QD:
- Patients (N=7131) received XARELTO 20 mg once daily (15 mg once daily in patients with moderate renal impairment defined as CrCl 30 to ≤50 mL/min)
Warfarin dose-adjusted
- (N=7133)
- Titrated to an INR range of 2.0 to 3.0
XARELTO® Effectively Reduced Risk of Stroke/SE2
- Stroke or SE event rates per 100 patient-years were:
- 2.4 (306/7090) in patients taking warfarin
- 2.1 (269/7081) in patients taking XARELTO®
- (HR [95% CI]: 0.88 [0.75-1.03]) P<0.001
XARELTO® Demonstrated Safety Profile vs warfarin2
- Major bleeding*: 3.6%/year (395/7111) with XARELTO® vs 3.5%/year (386/7125) with warfarin, HR (95% CI): 1.04 (0.90-1.20)
- ICH†: 0.5%/year (55/7111) with XARELTO® vs 0.7%/year (84/7125) with warfarin, HR (95% CI): 0.67 (0.47-0.93)
- GI bleeding‡: 2.0%/year (221/7111) with XARELTO® vs 1.2%/year (140/7125) with warfarin, HR (95% CI: 1.61 (1.30-1.99)
- Fatal bleeding§: 0.2%/year (27/7111) with XARELTO® vs 0.5%/year (55/7125) with warfarin, HR (95% CI): 0.50 (0.31 -0.79)
XARELTO® Renal Dosing Considerations Based on CrCl॥¶
Patients with CrCl ≤50mL/min# take 15 mg QD with the evening meal. Patients with CrCl >50 take 20mg QD with the evening meal. Periodically assess renal function as clinically indicated (ie, more frequently in situations in which renal function may decline) and adjust therapy accordingly. Consider dose adjustment or discontinuation of XARELTO® in patients who develop any renal failure while on XARELTO®.
Clinical efficacy and safety studies with XARELTO® did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, administration of XARELTO® 15 mg once daily will result in concentrations of rivaroxaban and pharmacodynamic activity similar to those observed in the ROCKET AF study. It is not known whether these concentrations will lead to similar stroke reduction and bleeding risk in patients with ESRD on dialysis as was seen in ROCKET AF.
*Major bleeding was defined as clinically overt bleeding associated with hemoglobin decrease ≥2 g/dl, transfusion of ≥2 units of packed red blood cells or whole blood, bleeding at a critical site, or with fatal outcomes (ISTH criteria).
†Intracranial bleeding events included intraparenchymal, intraventricular, subdural, subarachnoid, and/or epidural hematoma.
‡GI bleeding events included upper Gl, lower GI, and rectal bleeding.
§Fatal bleeding is adjudicated death with the primary cause of death from bleeding.
॥Calculate CrCl based on actual weight.
¶See section 8.6 of the full Prescribing Information for additional information.
#Patients with CrCl <30 mL/min were not studied, but administration of XARELTO® is expected to result in serum concentrations of rivaroxaban similar to those in patients with moderate renal impairment (CrCl 30 to <50 mL/min).
AF = atrial fibrillation; CI = confidence interval; CrCl = creatinine clearance; ESRD = end-stage renal disease; GI = gastrointestinal; HR = hazard ratio; ICH = intracranial hemorrhage; INR = international normalized ratio; ITT = intention-to-treat; QD = once daily; RWE = real-world evidence; SE = systemic embolism.
