The Clinical Associations With The Differences in Rivaroxaban Dosing in Patients with Atrial Fibrillation Stratified by three Renal Function Formulae
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Keywords
Atrial fibrillation , Bleeding events, Direct oral anticoagulant, Medication appropriateness, Renal function test, Stroke events
Abstract
Background: Clinical trials used Cockcroft-Gault (CG) formula to calculate the estimated glomerular filtration rate (eGFR) in order to dose rivaroxaban for patients with atrial fibrillation (AF). Objectives: The aim of this study is to evaluate rivaroxaban dosing appropriateness in patients with AF with or without renal impairment based on the CG formula and other formulae, including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and the isotope dilution mass spectrometry (IDMS) traceable Modification of Diet in Renal Disease (MDRD) Study equation and the associated clinical outcomes. Methodology: A retrospective cohort study conducted at Sultan Qaboos University Hospital (SQUH) from 1st January 2016 to 31st December 2020, included all adult patients (≥ 18 years) treated with rivaroxaban for AF and followed up for one year after starting the treatment. Results: Based on the CG formula, the rivaroxaban dose was inappropriately prescribed in 27% of the patients (21% overdosed and 6% underdosed). Higher baseline creatinine (P=0.0014) and concurrent use of antiplatelet therapy (P<0.001) were associated with the tendency to rivaroxaban overdosing. Higher Body Mass Index (BMI) (P=0.002), female sex (P=0.032), and CKD (P=0.003) were associated with rivaroxaban underdosing. The degree of agreement between the renal function tests when comparing MDRD vs CG and CKD-EPI vs CG in terms of estimated glomerular filtration rate/creatine clearance (eGFR/CrCl) calculation was moderate (κ=0.46) and poor (κ=0.00), respectively, while, in terms of rivaroxaban dose appropriateness was almost perfect (κ=0.82) and substantial (κ=0.77). Clinical outcomes measured by stroke and bleeding events were not significantly different according to the appropriateness of the rivaroxaban dose. Conclusion: This study has shown a relatively high consistency with the gold standard in dosing rivaroxaban in AF patients using CG formula. Treatment efficiency and safety were not affected by the proportion of dose inappropriateness found in this cohort.
References
2. de Souza Lima Bitar Y, Neto MG, Filho JAL, et al. Comparison of the New Oral Anticoagulants and Warfarin in Patients with Atrial Fibrillation and Valvular Heart Disease: Systematic Review and Meta-Analysis. Drugs R D. 2019;19(2):117-126. https://
doi.org/10.1007/s40268-019-0274-z
3. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart
Rhythm Society. J Am Coll Cardiol. 2014;64(21):e1-76. https://doi.org/10.1016/j.jacc.2014.03.022
4. Andrade J, Khairy P, Dobrev D, et al. The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms. Circ Res. 2014;114(9):1453-1468. https://doi.org/0.1161/CIRCRESAHA.114.303211
5. Kvasnicka T, Malikova I, Zenahlikova Z, et al. Rivaroxaban - Metabolism, Pharmacologic Properties and Drug Interactions. Curr Drug Metab. 2017;18(7):636-642. https://doi.org/10.2174/1389200218666170518165443
6. Yao X, Shah ND, Sangaralingham LR, et al. Non-Vitamin K Antagonist Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Renal Dysfunction. J Am Coll Cardiol. 2017;69(23):2779-2790. https://doi.org/10.21037/atm.2017.09.19
7. Noseworthy PA, Yao X, Abraham NS, et al. Direct Comparison of Dabigatran, Rivaroxaban, and Apixaban for Effectiveness and Safety in Nonvalvular Atrial Fibrillation. Chest. 2016;150(6):1302-1312. https://doi.org/10.1016/j.chest.2016.07.013
8. Hori M, Matsumoto M, Tanahashi N, et al. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –. Circ J. 2012;76(9):2104-2111. https://doi.org/10.1253/circj.cj-12-0454
9. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association
Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation. 2019;140(2):e125-e151. https://doi.org/10.1016/j.hrthm.2019.01.024
10. Pazmiño PA. Renal Risk Stratification Tool to Guide NOAC Dosing in Patients With Renal Dysfunction. J Am Coll Cardiol. 2017;70(21):2732-2733. https://doi.org/10.1016/j.jacc.2017.09.1093
11. Stacy ZA, Richter SK. Direct oral anticoagulants for stroke prevention in atrial fibrillation: treatment outcomes and dosing in special populations. Ther Adv Cardiovasc Dis. 2018;12(9):247-262. https://doi.org/10.1177/1753944718787384
12. Barón-Esquivias G, Marín F, Sanmartín Fernandez M. Rivaroxaban in patients with atrial fibrillation: from ROCKET AF to everyday practice. Expert Rev Cardiovasc Ther. 2017;15(5):403-413. https://doi.org/10.1080/14779072.2017.1309293
13. Khan SU, Singh M, Valavoor S, et al. Dual Antiplatelet Therapy After Percutaneous Coronary Intervention and Drug-Eluting Stents: A Systematic Review and Network Meta-Analysis. Circulation. 2020;142(15):1425-1436. https://doi.org/10.1161/
CIRCULATIONAHA.120.046308
14. Berkman SA. Prevention of Bleeding in Patients With Atrial Fibrillation Undergoing PCI (PIONEER): Three May End Up Being a Crowd. Clin Appl Thromb Hemost. 2018;24(3):393-395. https://doi.org/10.1177/1076029617710334
15. Mayet AY, Alsaqer AI, Alhammad AM, et al. Rivaroxaban prescribing in a Saudi tertiary care teaching hospital. Saudi Pharm J. 2018;26(6):775-779. https://doi.org/10.1016/j.jsps.2018.04.007
16. Fleiss JL. Measuring nominal scale agreement among many raters. Psychological Bulletin. 1971;76(5):378-382. https://doi.org/10.1037/h0031619
17. Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics. 1977;33(1):159-174. https://doi.org/10.2307/2529310
18. Andrade JG, Hawkins NM, Fordyce CB, et al. Variability in Non-Vitamin K Antagonist Oral Anticoagulants Dose Adjustment in Atrial Fibrillation Patients With Renal Dysfunction: The Influence of Renal Function Estimation Formulae. Can J Cardiol.
2018;34(8):1010-1018. https://doi.org/10.1016/j.cjca.2018.04.019
19. Ablefoni K, Buchholz A, Ueberham L, et al. Initial rivaroxaban dosing in patients with atrial fibrillation. Clin Cardiol. 2019;42(10):873-880. https://doi.org/10.1002/clc.23235
20. Du H, Wilson D, Ambler G, et al. Small Vessel Disease and Ischemic Stroke Risk During Anticoagulation for Atrial Fibrillation After Cerebral Ischemia. Stroke. 2021;52(1):91-99. https://doi.org/10.1161/STROKEAHA.120.029474
21. Pan D, Rong X, Li H, et al. Anti-platelet Therapy Is Associated With Lower Risk of Dementia in Patients With Cerebral Small Vessel Disease. Front Aging Neurosci. 2022;14:788407. https://doi.org/10.3389/fnagi.2022.788407
22. Al-Maqbali JS, Taqi A, Al-Hamadani B, et al. Levels of agreement among clinical pharmacists on the impact of pharmaceutical interventions in Oman: A retrospective analysis. Pharmacy Practice 2022;20(3):2708. https://doi.org/10.18549/
pharmpract.2022.3.2708
23. Yi-Hsin, Chan T-FC, Hsin-Fu Lee, et al. Different Renal Function Equations and Dosing of Direct Oral Anticoagulants in Atrial Fibrillation. JACC: ASIA. 2022;2(1):46-58. https://doi.org/10.1016/j.jacasi.2021.11.006
24. Michels WM, Grootendorst DC, Verduijn M, et al. Performance of the Cockcroft-Gault, MDRD, and new CKD-EPI formulas in relation to GFR, age, and body size. Clin J Am Soc Nephrol. 2010;5(6):1003-1009. https://doi.org/10.2215/CJN.06870909
25. Pérez Cabeza AI, Chinchurreta Capote PA, González Correa JA, et al. Discrepancies between the use of MDRD-4 IDMS and CKD-EPI equations, instead of the Cockcroft-Gault equation, in the determination of the dosage of direct oral anticoagulants in
patients with non-valvular atrial fibrillation. Med Clin (Barc). 2018;150(3):85-91. https://doi.org/10.1016/j.medcle.2017.12.005
26. Duerschmied D, Brachmann J, Darius H, et al. Antithrombotic therapy in patients with non-valvular atrial fibrillation undergoing percutaneous coronary intervention: should we change our practice after the PIONEER AF-PCI and RE-DUAL PCI trials? Clin Res
Cardiol. 2018;107(7):533-538. https://doi.org/10.1007/s00392-018-1242-2
27. Lee SR, Choi EK, Han KD, et al. Optimal Rivaroxaban Dose in Asian Patients With Atrial Fibrillation and Normal or Mildly Impaired Renal Function. Stroke. 2019;50(5):1140-1148. https://doi.org/10.1161/STROKEAHA.118.024210
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