Stroke Risk and Efficacy of Apixaban in Atrial Fibrillation Patients with Moderate Chronic Kidney Disease

Background: Apixaban is superior to aspirin for the prevention of stroke in patients with atrial fibrillation. Apixaban is partially renally excreted and may accumulate in patients with renal impairment. Methods: We evaluated the efficacy and safety of apixaban 5 mg twice daily (2.5 mg twice daily in selected patients) compared with aspirin 81 to 324 mg daily in 1697 patients with stage III chronic kidney disease (CKD) enrolled in the Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or are Unsuitable for Vitamin K Antagonist Treatment (AVERROES) trial. Primary outcome was all stroke and non-central nervous system emboli. Results: Compared with patients with estimated glomerular filtration rates (eGFRs) >= 60 mL/min per 1.73 m(2), stage III CKD patients (n = 1697; 30% of the cohort; mean eGFR 49 mL/min per 1.73 m(2)) were older (mean age 75 v 68 years) with more frequent hypertension, diabetes, heart failure, and previous stroke (all P < .01). Stage III CKD was an independent predictor of primary events (hazard ratio [HR] 1.6; P = .01) and major hemorrhage (HR 2.2; P = .02). Apixaban significantly reduced primary events by 68% (5.6% per year on aspirin v 1.8% per year on apixaban; HR 0.32; 95% confidence interval [CI] 0.18-0.55; P < .001) for stage III CKD participants and by 43% (2.8% per year on aspirin v 1.6% per year on apixaban; HR0.57; 95% CI 0.37-0.87; P = .009) for patients with eGFRs >= 60 mL/min per 1.73 m(2) (P for interaction = .10). There was no significant difference in major hemorrhage in stage III CKD patients by treatment: 2.2% per year with aspirin versus 2.5% per year with apixaban (HR 1.2; 95% CI 0.65-2.1). Conclusions: Stage III CKD was an independent predictor of stroke in atrial fibrillation patients taking aspirin. Among stage III CKD patients, apixaban significantly reduced stroke relative to aspirin without a significant increase in major hemorrhage.