Abstract: TH-PO460
Apixaban versus Warfarin in Patients with Atrial Fibrillation (AF) and Stage 4 CKD
Session Information
- CKD: Epidemiology, Outcomes - Cardiovascular - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 303 CKD: Epidemiology, Outcomes - Cardiovascular
Authors
- Stanifer, John W., Duke University, Durham, North Carolina, United States
- Chertow, Glenn Matthew, Stanford University School of Medicine, Palo Alto, California, United States
- Hohnloser, Stefan H, J. W. Goethe University, Division of Clinical Electrophysiology, Frankfurt, Germany
- Wojdyla, Daniel, Duke Clinical Research Institute, Durham, North Carolina, United States
- Garonzik, Samira, BMS, Princeton, New Jersey, United States
- Byon, Wonkyung, Pfizer, Groton, Connecticut, United States
- Lopes, Renato D, Duke Clinical Research Institute, Durham, North Carolina, United States
- Alexander, John H, Duke Clinical Research Institute, Durham, North Carolina, United States
- Wallentin, Lars, Uppsala Clinical Research Center, Uppsala, Sweden
- Granger, Christopher B., Duke Clinical Research Institute, Durham, North Carolina, United States
Background
Limited safety data exist for direct-acting oral anticoagulants in patients with advanced CKD. In Apixaban for Reduction of Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, we evaluated the effects of apixaban vs. warfarin in stage 4 CKD.
Methods
ARISTOTLE included patients with AF with a serum creatinine ≤2.5 mg/dL and estimated CrCl ≥25 mL/min. Apixaban dose was 5 mg bid or 2.5 mg bid if 2 of 3 criteria were met: age ≥80, weight ≤60 kg or serum creatinine ≥1.5 mg/dL. We used Cox proportional hazard models to analyze treatment effect stratified by CrCl category (< 30 vs ≥ 30mL/min). We also evaluated drug exposure by apixaban dose for patients with CrCl <30mL/min.
Results
Overall 269 patients (median age 81; 61% women) had a CrCl <30 mL/min. The effect of apixaban vs warfarin on stroke or systemic embolism was similar across CrCl categories (p interaction=0.50). For those with CrCl <30 mL/min, major bleeding occurred in 7 patients with apixaban and 19 with warfarin (HR 0.34; 95% CI 0.14-0.79), and the median apixaban drug exposure was 5512 ng/mL*hr (n=12) for 5mg and 2792 ng/ml*hr (n=19) for 2.5mg. The relative safety of apixaban was similar across CrCl categories (Table).
Conclusion
Among patients with Stage 4 CKD in ARISTOTLE, those randomized to apixaban experienced lower bleeding rates compared with warfarin, consistent with the overall population. Studies evaluating the safety and efficacy of apixaban in patients with advanced CKD, including end-stage kidney disease, are needed.
Bleeding rates per 100 patient-years and hazard ratios for apixaban vs. warfarin
| Bleeding Rates (n/N) CrCl <30 mL/min | Bleeding rates (n/N) CrCl ≥30 mL/min | Interaction p-value | ||||||
| Apixaban | Warfarin | HR (95% CI) | Apixaban | Warfarin | HR (95% CI) | |||
| Apixaban 2.5 mg*/placebo | Major bleeding | 3.42 (4/87) | 11.1 (11/85) | 0.34 (0.11-1.07) | 3.25 (16/337) | 5.75 (26/317) | 0.57 (0.31-1.07) | 0.41 |
| Major or CRNM bleeding | 4.28 (5/87) | 17.9 (17/85) | 0.27 (0.20-0.73) | 5.14 (25/337) | 8.08 (36/317) | 0.64 (0.38-1.06) | 0.12 | |
| Apixaban 5.0 mg/placebo | Major bleeding | 4.39 (3/48) | 13.3 (8/47) | 0.34 (0.09-1.29) | 2.08 (303/8578) | 2.91 (415/8567) | 0.72 (0.62-0.83) | 0.26 |
| Major or CRNM bleeding | 7.45 (5/48) | 15.0 (9/47) | 0.51 (0.17-1.53) | 4.01 (575/8578) | 5.83 (812/8567) | 0.69 (0.62-0.77) | 0.56 | |
| *For those who met 2 of 3 dose-reduction criteria CrCl=creatinine clearance; CRNM=clinically relevant non-major; HR=hazard ratio. | ||||||||
Funding
- Commercial Support –