Miklos Rohla1,2, Ladislav Pecen3, Roberto Cemin4, Giuseppe Patti5, Jolanta M Siller-Matula6,7, Renate B Schnabel8, Kurt Huber1,9, Paulus Kirchhof10, Raffaele De Caterina11. 1. 3 Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenhospital, Vienna, Austria (M.R., K.H.). 2. Institute for Cardiometabolic Diseases, Karl Landsteiner Society, St. Pölten, Austria (M.R.). 3. Medical Faculty Pilsen, Charles University, Czech Republic (L.P.). 4. Department of Cardiology, San Maurizio Regional Hospital of Bolzano, Italy (R.C.). 5. University of Eastern Piedmont, Maggiore della Carità Hospital of Novara, Italy (G.P.). 6. Department of Cardiology, Medical University of Vienna, Austria (J.M.S.-M.). 7. Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CEPT), Medical University of Warsaw, Poland (J.M.S.-M.). 8. University Heart Center Hamburg, Clinic for General and Interventional Cardiology, Hamburg, Germany and DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Luebeck, Germany (R.B.S.). 9. Sigmund Freud University, Medical School, Vienna, Austria (K.H.). 10. University of Birmingham Institute of Cardiovascular Sciences, University of Birmingham, UHB and SWBH NHS Trusts, United Kingdom (P.K.). 11. Chair of Cardiology, University of Pisa and Cardiology Division, Pisa University Hospital, Italy (R.D.C.).
Abstract
BACKGROUND: The Cockcroft-Gault formula is recommended to determine a renal indication for dose reduction of dabigatran, edoxaban, and rivaroxaban. Nephrology guidelines now recommend the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae as more accurate estimates of glomerular filtration rate. METHODS: We analyzed anticoagulated patients with atrial fibrillation who were enrolled in the Prevention of Thromboembolic Events - European Registry in Atrial Fibrillation (PREFER in AF). The proportion of patients with dissimilar renal dosing indications was assessed when applying Cockcroft-Gault, MDRD, or CKD-EPI. Thromboembolic and major bleeding events at 1 year were compared in patients in whom Cockcroft-Gault and CKD-EPI provided concordant or discordant results around a threshold of 50 mL/minute. RESULTS: Out of 1288 patients with atrial fibrillation with chronic kidney disease in whom Cockcroft-Gault suggested a dose reduction of dabigatran, edoxaban, or rivaroxaban (creatinine clearance ≤50 mL/minutes), 19% and 16% were reclassified to the respective higher doses, and 24% and 23% to the respective lower doses by applying the MDRD and CKD-EPI formulae, respectively. In patients potentially receiving a different dose of dabigatran, edoxaban, or rivaroxaban when using CKD-EPI, we observed an excess of thromboembolic events (4.1% versus 0.8%; odds ratio, 5.5 [95% CI, 1.5-20.8]; P=0.01). Major bleeding rates were nonsignificantly different in the discordance versus concordance group (5.7% versus 2.7%; odds ratio, 2.2 [95% CI, 0.9-5.6]; P=0.09). CONCLUSIONS: The MDRD and CKD-EPI formulae suggest a different dosing in up to a quarter of anticoagulated patients with atrial fibrillation. This seems to impact hard outcomes.
BACKGROUND: The Cockcroft-Gault formula is recommended to determine a renal indication for dose reduction of dabigatran, edoxaban, and rivaroxaban. Nephrology guidelines now recommend the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formulae as more accurate estimates of glomerular filtration rate. METHODS: We analyzed anticoagulated patients with atrial fibrillation who were enrolled in the Prevention of Thromboembolic Events - European Registry in Atrial Fibrillation (PREFER in AF). The proportion of patients with dissimilar renal dosing indications was assessed when applying Cockcroft-Gault, MDRD, or CKD-EPI. Thromboembolic and major bleeding events at 1 year were compared in patients in whom Cockcroft-Gault and CKD-EPI provided concordant or discordant results around a threshold of 50 mL/minute. RESULTS: Out of 1288 patients with atrial fibrillation with chronic kidney disease in whom Cockcroft-Gault suggested a dose reduction of dabigatran, edoxaban, or rivaroxaban (creatinine clearance ≤50 mL/minutes), 19% and 16% were reclassified to the respective higher doses, and 24% and 23% to the respective lower doses by applying the MDRD and CKD-EPI formulae, respectively. In patients potentially receiving a different dose of dabigatran, edoxaban, or rivaroxaban when using CKD-EPI, we observed an excess of thromboembolic events (4.1% versus 0.8%; odds ratio, 5.5 [95% CI, 1.5-20.8]; P=0.01). Major bleeding rates were nonsignificantly different in the discordance versus concordance group (5.7% versus 2.7%; odds ratio, 2.2 [95% CI, 0.9-5.6]; P=0.09). CONCLUSIONS: The MDRD and CKD-EPI formulae suggest a different dosing in up to a quarter of anticoagulated patients with atrial fibrillation. This seems to impact hard outcomes.
Authors: Adam J Rose; Jong Soo Lee; Dan R Berlowitz; Weisong Liu; Avijit Mitra; Hong Yu Journal: BMC Health Serv Res Date: 2021-12-18 Impact factor: 2.655