August 28, 2011European Heart Journal
Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment
Why the study?
Patients with non-valvular AF and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation.
Does dose-adjusted rivaroxaban reduce stroke or systemic embolism compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment?
Key Points
- This research aims to compare the efficacy and safety of rivaroxaban against warfarin in preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation and moderate renal impairment.
- 14,264 patients with atrial fibrillation were randomized in a double-blind trial.
- Participants received either rivaroxaban 20 mg/day (15 mg if CrCl 30-49 mL/min) or dose-adjusted warfarin.
- The primary endpoint measured was stroke or systemic embolism, with safety assessed through major and clinically relevant non-major bleeding.
- In patients with CrCl 30-49 mL/min, stroke/systemic embolism rates were 2.32 per 100 patient-years for rivaroxaban vs. 2.77 for warfarin (HR 0.84; 95% CI 0.57-1.23).
- Intention-to-treat analysis showed comparable results (HR 0.86; 95% CI 0.63-1.17).
- Fatal bleeding rates were lower for rivaroxaban at 0.28% per 100 patient-years compared to 0.74% for warfarin (P = 0.047).
Structured PICO
Does dose-adjusted rivaroxaban reduce stroke or systemic embolism compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment?
P
Population
14,264 patients with non-valvular atrial fibrillation (AF), including a subgroup of 2,950 (20.7%) patients with moderate renal impairment (creatinine clearance 30-49 mL/min) with a mean age of 79 years.
I
Intervention
Rivaroxaban 20 mg/day (dose-adjusted to 15 mg/day for patients with creatinine clearance 30-49 mL/min)
C
Comparator
Dose-adjusted warfarin (target international normalized ratio 2.0-3.0)
O
Outcome
Stroke or systemic embolismcomposite
In patients with non-valvular atrial fibrillation and moderate renal impairment, dose-adjusted rivaroxaban (15 mg/day) provides consistent efficacy for stroke prevention and significantly reduces fatal bleeding compared to dose-adjusted warfarin.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Given the prevalence and morbidity associated with atrial fibrillation, and the well-known difficulties with warfarin use, it is exciting to have an alternative which was documented in this study to be effective with no increase in significant bleeding.”
JTJeffrey T. HaRenal and metabolic division, George Institute for Global Health
“This study adds important safety data on the use of rivaroxaban in patients with reduced kidney function including... in whom the risks and benefits of rivaroxaban use is most uncertain.”
Implication
Supports rivaroxaban over warfarin for AF with moderate renal impairment; extends evidence to high-risk patients with elevated stroke and bleeding rates.
Abstract
AIMS: Patients with non-valvular atrial fibrillation (AF) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation. Rivaroxaban, an oral, direct factor Xa inhibitor metabolized predominantly by the liver, preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages. METHODS AND RESULTS: We randomized 14 264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day [15 mg/day if creatinine clearance (CrCl) 30-49 mL/min] or dose-adjusted warfarin (target international normalized ratio 2.0-3.0). Compared with patients with CrCl >50 mL/min (mean age 73 years), the 2950 (20.7%) patients with CrCl 30-49 mL/min were older (79 years) and had higher event rates irrespective of study treatment. Among those with CrCl 30-49 mL/min, the primary endpoint of stroke or systemic embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs. 2.77 per 100 patient-years with warfarin [hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.57-1.23] in the per-protocol population. Intention-to-treat analysis yielded similar results (HR 0.86; 95% CI 0.63-1.17) to the per-protocol results. Rates of the principal safety endpoint (major and clinically relevant non-major bleeding: 17.82 vs. 18.28 per 100 patient-years; P = 0.76) and intracranial bleeding (0.71 vs. 0.88 per 100 patient-years; P = 0.54) were similar with rivaroxaban or warfarin. Fatal bleeding (0.28 vs. 0.74% per 100 patient-years; P = 0.047) occurred less often with rivaroxaban. CONCLUSION: Patients with AF and moderate renal insufficiency have higher rates of stroke and bleeding than those with normal renal function. There was no evidence of heterogeneity in treatment effect across dosing groups. Dose adjustment in ROCKET-AF yielded results consistent with the overall trial in comparison with dose-adjusted warfarin.
Discussion
No takes yet. Share an insight, caveat, or question.
Cite This Study
Fox et al. (2011) studied this question.