Xiaoxi Yao1,2,3, Jonathan W Inselman1,2, Joseph S Ross4,5, Rima Izem6, David J Graham7, David B Martin8, Aliza M Thompson9, Mary Ross Southworth9, Konstantinos C Siontis3, Che G Ngufor1,10, Karl A Nath11, Nihar R Desai5, Brahmajee K Nallamothu12, Rajiv Saran13, Nilay D Shah1,2,14, Peter A Noseworthy1,3. 1. Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery (X.Y., J.W.I., C.G.N., N.D.S., P.A.N.), and Department of Internal Medicine, Mayo Clinic, Rochester, MN. 2. Division of Health Care Policy and Research, Department of Health Sciences Research (X.Y., J.W.I., N.D.S.), and Department of Internal Medicine, Mayo Clinic, Rochester, MN. 3. Department of Cardiovascular Medicine (X.Y., K.C.S., P.A.N.), and Department of Internal Medicine, Mayo Clinic, Rochester, MN. 4. Department of Internal Medicine, Section of General Internal Medicine, Yale School of Medicine, New Haven, CT (J.S.R.). 5. Center for Outcomes Research and Evaluation, Yale-New Haven Hospital, New Haven, CT (J.S.R., N.R.D.). 6. Division of Biometrics and Epidemiology, Children's National Research Institute, Washington, D.C. (R.I.). 7. Office of Surveillance and Epidemiology (D.J.G.), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD. 8. Office of Medical Policy (D.B.M.), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD. 9. Division of Cardiovascular and Renal Products (A.M.T, M.R.S.), Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD. 10. Division of Biomedical Statistics and Informatics, Department of Health Sciences Research (C.G.N.), and Department of Internal Medicine, Mayo Clinic, Rochester, MN. 11. Division of Nephrology and Hypertension (K.A.N.), and Department of Internal Medicine, Mayo Clinic, Rochester, MN. 12. Division of Cardiovascular Medicine, Department of Internal Medicine (B.K.N.), University of Michigan, Ann Arbor. 13. Department of Internal Medicine (R.S.), University of Michigan, Ann Arbor. 14. OptumLabs, Cambridge, MA (N.D.S.).
Abstract
BACKGROUND: Patients with atrial fibrillation and severely decreased kidney function were excluded from the pivotal non-vitamin K antagonist oral anticoagulants (NOAC) trials, thereby raising questions about comparative safety and effectiveness in patients with reduced kidney function. The study aimed to compare oral anticoagulants across the range of kidney function in patients with atrial fibrillation. METHODS AND RESULTS: Using a US administrative claims database with linked laboratory data, 34 569 new users of oral anticoagulants with atrial fibrillation and estimated glomerular filtration rate ≥15 mL/(min·1.73 m2) were identified between October 1, 2010 to November 29, 2017. The proportion of patients using NOACs declined with decreasing kidney function-73.5%, 69.6%, 65.4%, 59.5%, and 45.0% of the patients were prescribed a NOAC in estimated glomerular filtration rate ≥90, 60 to 90, 45 to 60, 30 to 45, 15 to 30 mL/min per 1.73 m2 groups, respectively. Stabilized inverse probability of treatment weighting was used to balance 4 treatment groups (apixaban, dabigatran, rivaroxaban, and warfarin) on 66 baseline characteristics. In comparison to warfarin, apixaban was associated with a lower risk of stroke (hazard ratio [HR], 0.57 [0.43-0.75]; P<0.001), major bleeding (HR, 0.51 [0.44-0.61]; P<0.001), and mortality (HR, 0.68 [0.56-0.83]; P<0.001); dabigatran was associated with a similar risk of stroke but a lower risk of major bleeding (HR, 0.57 [0.43-0.75]; P<0.001) and mortality (HR, 0.68 [0.48-0.98]; P=0.04); rivaroxaban was associated with a lower risk of stroke (HR, 0.69 [0.51-0.94]; P=0.02), major bleeding (HR, 0.84 [0.72-0.99]; P=0.04), and mortality (HR, 0.73 [0.58-0.91]; P=0.006). There was no significant interaction between treatment and estimated glomerular filtration rate categories for any outcome. When comparing one NOAC to another NOAC, there was no significant difference in mortality, but some differences existed for stroke or major bleeding. No relationship between treatments and falsification end points was found, suggesting no evidence for substantial residual confounding. CONCLUSIONS: Relative to warfarin, NOACs are used less frequently as kidney function declines. However, NOACs appears to have similar or better comparative effectiveness and safety across the range of kidney function.
BACKGROUND:Patients with atrial fibrillation and severely decreased kidney function were excluded from the pivotal non-vitamin K antagonist oral anticoagulants (NOAC) trials, thereby raising questions about comparative safety and effectiveness in patients with reduced kidney function. The study aimed to compare oral anticoagulants across the range of kidney function in patients with atrial fibrillation. METHODS AND RESULTS: Using a US administrative claims database with linked laboratory data, 34 569 new users of oral anticoagulants with atrial fibrillation and estimated glomerular filtration rate ≥15 mL/(min·1.73 m2) were identified between October 1, 2010 to November 29, 2017. The proportion of patients using NOACs declined with decreasing kidney function-73.5%, 69.6%, 65.4%, 59.5%, and 45.0% of the patients were prescribed a NOAC in estimated glomerular filtration rate ≥90, 60 to 90, 45 to 60, 30 to 45, 15 to 30 mL/min per 1.73 m2 groups, respectively. Stabilized inverse probability of treatment weighting was used to balance 4 treatment groups (apixaban, dabigatran, rivaroxaban, and warfarin) on 66 baseline characteristics. In comparison to warfarin, apixaban was associated with a lower risk of stroke (hazard ratio [HR], 0.57 [0.43-0.75]; P<0.001), major bleeding (HR, 0.51 [0.44-0.61]; P<0.001), and mortality (HR, 0.68 [0.56-0.83]; P<0.001); dabigatran was associated with a similar risk of stroke but a lower risk of major bleeding (HR, 0.57 [0.43-0.75]; P<0.001) and mortality (HR, 0.68 [0.48-0.98]; P=0.04); rivaroxaban was associated with a lower risk of stroke (HR, 0.69 [0.51-0.94]; P=0.02), major bleeding (HR, 0.84 [0.72-0.99]; P=0.04), and mortality (HR, 0.73 [0.58-0.91]; P=0.006). There was no significant interaction between treatment and estimated glomerular filtration rate categories for any outcome. When comparing one NOAC to another NOAC, there was no significant difference in mortality, but some differences existed for stroke or major bleeding. No relationship between treatments and falsification end points was found, suggesting no evidence for substantial residual confounding. CONCLUSIONS: Relative to warfarin, NOACs are used less frequently as kidney function declines. However, NOACs appears to have similar or better comparative effectiveness and safety across the range of kidney function.
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