Scoping Review to Identify Apixaban and Rivaroxaban Dosing Regimens Used for Managing Atrial Fibrillation or Venous Thromboembolism in individuals with Advanced Non-Dialysis Dependent Chronic Kidney Disease
Why this work is in the frame
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Bibliographic record
Abstract
The purpose of this scoping review is to identify and summarize the dosing regimens of apixaban and rivaroxaban used in the management of atrial fibrillation (AF) or venous thromboembolism (VTE) in patients with advanced chronic kidney disease (CKD) (e.g., CKD stage 4 and 5 [non-dialysis dependent]). Impaired kidney function can significantly affect the pharmacokinetics and safety of anticoagulant therapies. Apixaban and rivaroxaban are direct oral anticoagulants (DOACs) that are commonly utilized in clinical practice. However, pivotal clinical trials of apixaban and rivaroxaban excluded patients with a creatinine clearance < 25 mL/min and < 30 mL/min respectively, creating uncertainty regarding a safe and effective dose regimen for this population (1-8). Additional studies have evaluated apixaban and rivaroxaban yielding mixed findings (9-15). By analyzing the available evidence, this review aims to provide a comprehensive overview of the use of rivaroxaban and apixaban in advanced CKD, help guide clinical decision-making and highlight gaps in knowledge that may inform future research in this area. 1. Agnelli G, Buller HR, Cohen A, et al; AMPLIFY-EXT Investigators. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013a;368(8):699-708. 2. Agnelli G, Buller HR, Cohen A, et al; AMPLIFY Investigators. Oral apixaban for the treatment of acute venous thromboembolism. N Engl J Med. 2013b;369(9):799-808. 3. Connolly SJ, Eikelboom J, Joyner C, et al; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806-817. 4. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992. 5. Patel MR., Mahaffrey KW., Garg J., Pan G., Singer DE., Werner MD., et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011 Sept 8. 365(10): 883-891. 6. EINSTEIN Investigators; Bauersachs R, Berkowitz SD, Brenner B, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010 Dec 23;363(26):2499-510. doi: 10.1056/NEJMoa1007903. 7. EINSTEIN–PE Investigators; Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, Minar E, Chlumsky J, Verhamme P, Wells P, Agnelli G, Cohen A, Berkowitz SD, Bounameaux H, Davidson BL, Misselwitz F, Gallus AS, Raskob GE, Schellong S, Segers A. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012 Apr 5;366(14):1287-97. 8. Weitz JI, Lensing AWA, Prins MH, Bauersachs R, Beyer-Westendorf J, Bounameaux H, Brighton TA, Cohen AT, Davidson BL, Decousus H, Freitas MCS, Holberg G, Kakkar AK, Haskell L, van Bellen B, Pap AF, Berkowitz SD, Verhamme P, Wells PS, Prandoni P; EINSTEIN CHOICE Investigators. Rivaroxaban or Aspirin for Extended Treatment of Venous Thromboembolism. N Engl J Med. 2017 Mar 30;376(13):1211-1222. 9. Weir MR, Ashton V, Moore KT, Shrivastava S, Peterson ED, Ammann EM. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and stage IV-V chronic kidney disease. Am Heart J. 2020 May; 223:3-11. 10. Coleman CI, Kreutz R, Sood NA, Bunz TJ, Eriksson D, Meinecke AK, Baker WL. Rivaroxaban versus warfarin in patients with nonvalvular atrial fibrillation and severe kidney disease or undergoing hemodialysis. Am J Med. 2019 Sep;132(9):1078-1083. 11. Ha JT, Scaria A, Andrade J, Badve SV, Birks P, Bota SE, et al. Safety and effectiveness of rivaroxaban versus warfarin across GFR levels in atrial fibrillation: A population-based study in Australia and Canada. Kidney Med. 2023 May 16;5(7):100675. 12. Ha JT, Neuen BL, Cheng LP, et al. Benefits and harms of oral anticoagulant therapy in chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2019;171(3):181-189. 13. Joglar JA, Chung MK, Armbruster AL, et al. 2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation: a report of the American College of Cardiology/American Heart Association joint committee on clinical practice guidelines. Circulation. 2024;149(1):e1-e156. 14. Andrade JG., Aguilar M., Atzema C., Bell A., Cairnes JA., Cheung CC., et al. The 2020 Canadian cardiovascular society/Canadian heart rhythm society comprehensive guidelines for the management of atrial fibrillation. Can J Cardiol. 2020 Dec; 36(12): 1847-1948. 15. Fox KA, Piccini JP, Wojdyla D, et al. Prevention of stroke and systemic embolism with rivaroxaban compared with warfarin in patients with non-valvular atrial fibrillation and moderate renal impairment. Eur Heart J. 2011;32(19):2387-2394.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.004 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.002 | 0.006 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it