Influence of Kidney Function Estimation Methods on Eligibility for Edoxaban Population Impact of the US Food and Drug Administration’s Approach for Its Product Labeling
2016; Lippincott Williams & Wilkins; Volume: 134; Issue: 15 Linguagem: Inglês
10.1161/circulationaha.116.024333
ISSN1524-4539
AutoresSean D. Pokorney, Peter Shrader, Laine Thomas, Gregg C. Fonarow, Peter R. Kowey, Daniel E. Singer, Jack Ansell, Bernard J. Gersh, Kenneth W. Mahaffey, Elaine M. Hylek, Alan S. Go, Jonathan P. Piccini, Eric D. Peterson,
Tópico(s)Advanced Causal Inference Techniques
ResumoHomeCirculationVol. 134, No. 15Influence of Kidney Function Estimation Methods on Eligibility for Edoxaban Population Impact of the US Food and Drug Administration's Approach for Its Product Labeling Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBInfluence of Kidney Function Estimation Methods on Eligibility for Edoxaban Population Impact of the US Food and Drug Administration's Approach for Its Product Labeling Sean D. Pokorney, MD, MBA, Peter Shrader, MA, Laine Thomas, PhD, Gregg C. Fonarow, MD, Peter R. Kowey, MD, Daniel E. Singer, MD, MA, Jack Ansell, MD, Bernard J Gersh, MB, ChB, DPhil, Kenneth W. Mahaffey, MD, Elaine M. Hylek, MD, MPH, Alan S. Go, MD, Jonathan P. Piccini, MD, MHS and Eric D. Peterson, MD, MPHFor the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Investigators Sean D. PokorneySean D. Pokorney From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Peter ShraderPeter Shrader From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Laine ThomasLaine Thomas From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Gregg C. FonarowGregg C. Fonarow From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Peter R. KoweyPeter R. Kowey From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Daniel E. SingerDaniel E. Singer From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Jack AnsellJack Ansell From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Bernard J GershBernard J Gersh From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Kenneth W. MahaffeyKenneth W. Mahaffey From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Elaine M. HylekElaine M. Hylek From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Alan S. GoAlan S. Go From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). , Jonathan P. PicciniJonathan P. Piccini From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). and Eric D. PetersonEric D. Peterson From the Division of Cardiology, Duke University Medical Center, Durham, NC (S.D.P., J.P.P., E.D.P.); Duke Clinical Research Institute, Durham, NC (S.D.P., P.S., L.T., J.P.P., E.D.P.); Division of Cardiology, University of California Los Angeles (G.C.F.); Lankenau Institute for Medical Research, Wynnewood, PA (P.R.K.); Harvard Medical School, Massachusetts General Hospital, Boston (D.E.S.); Hofstra North Shore/Long Island School of Medicine, Hempstead, NY (J.A.); Mayo Clinic College of Medicine, Rochester, MN (BJ.G.); Department of Medicine, Stanford University School of Medicine, Palo Alto, CA (K.W.M.); Boston University School of Medicine, Boston, MA (E.M.H.); and Kaiser Permanente, Oakland, CA (A.S.G.). and For the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) Investigators Originally published11 Oct 2016https://doi.org/10.1161/CIRCULATIONAHA.116.024333Circulation. 2016;134:1122–1124Non-vitamin K antagonist oral anticoagulants (NOACs) have similar to superior safety and efficacy compared with warfarin.1 The US Food and Drug Administration (FDA) issued a "black box warning" for edoxaban in atrial fibrillation (AF) patients with estimated creatinine clearance (eCrCl) >95mL/min due to concerns regarding reduced efficacy. This warning was not adopted by European or Japanese regulatory agencies. There are limited data on the prevalence and clinical characteristics of AF patients with eCrCl>95mL/min in community practice.Data were studied from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a prospective registry of 10 135 AF patients from 176 primary care, cardiologist, and electrophysiologist outpatient US clinics. Patients were ≥18 years of age with nonreversible AF and were enrolled June 2010 through August 2011. We excluded 820 patients (8%) with missing baseline eCrCl. Patients were stratified by baseline Cockroft-Gault eCrCl. Differences between groups were assessed by Χ2 and Wilcoxon rank-sum tests, as appropriate. The Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations calculated estimated glomerular filtration rates (eGFR) for comparison to Cockroft-Gault. Written informed consent was obtained for registry enrollment. The Duke Institutional Review Board approved this study.Among 9315 AF patients, median age was 75 years (interquartile range [IQR] 67–82 years). Median eCrCl was 70mL/min (IQR 50-97mL/min), and 26% (n=2 439) had eCrCl>95mL/min (Figure). Compared with patients with eCrCl ≤95mL/min, those with eCrCl>95mL/min were younger (median 64 [IQR 58–70] versus 78 [IQR 72–83] years, P<0.0001), were more likely male (74% versus 52%, P<0.0001), and had greater weight (median 109 versus 80 kg, P<0.0001) and lower prevalence of hypertension (81% versus 85%, P<0.0001), congestive heart failure (27% versus 36%, P<0.0001), and prior cerebrovascular events (10% versus 18%, P 95mL/min versus not: median 3 (IQR 2–4) versus 4 (IQR 3–5), P 95mL/min cutoff. If the MDRD equation was applied, 12% (n=1083) had eGFR>95mL/min; if CKD-EPI was used, only 7% (n=722) had eGFR>95mL/min (Figure).Data from ORBIT-AF demonstrated that 26% of AF patients in ambulatory practice had eCrCl>95 mL/min by Cockroft-Gault. This rate fell as low as 7% if alternative methods estimated renal function. These rates in community practice were slightly higher than the 22% rate of eCrCl>95mL/min by Cockroft-Gault and 6% by CKD-EPI in the edoxaban trial.2Cockroft-Gault was developed to identify patients with chronic kidney disease. It has been the industry and regulatory standard for pharmacokinetic studies and has been used for cardiovascular guidelines drug dosing recommendations.3 Cockroft-Gault determined dosing in randomized trials for dabigatran, rivaroxaban, and edoxaban, and these medications' package inserts use Cockroft-Gault for determining appropriate dosing.The FDA performed a post hoc analysis of the edoxaban trial data and found an association between Cockroft-Gault eCrCl>95mL/min and higher ischemic stroke rates, with a similar trend identified by the trial investigators.2 Cockroft-Gault has been less accurate in patients with high creatinine clearance.4 The CKD-EPI equation was developed for greater estimating accuracy of renal function in patients with higher eGFRs.5 In clinical practice, laboratories often only provide MDRD, which is widely used for chronic kidney disease staging.Our data demonstrated that more than 1 in 4 community-based AF patients were affected by the FDA's edoxaban black box warning, although this number decreases to as low as 1 in 15 patients depending on the formula used. These data should alert clinicians to investigate which formula they and their local laboratory use to estimate renal function, keeping in mind that the clinical trials and medication labels for all NOACs, except apixaban, used Cockroft-Gault to determine medication dosing.Sources of FundingThe ORBIT-AF registry is sponsored by Janssen Scientific Affairs, LLC, Raritan, NJ.DisclosuresDr Pokomey reports modest research support from Astra Zeneca, Boston Scientific, and Gilead; and modest Consultant/Advisory Board support from Boston Scientific and Medtronic. Dr Fonarow reports modest Consultant/Advisory Board support from Janssen Pharmaceuticals. Dr Kowey reports modest Consultant/Advisory Board support from Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, Portola, Merck, Sanofi, and Daiichi Sankyo. Dr Singer reports significant consulting fees from Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Pfizer, and CSL Behring; significant research grant from Bristol-Myers Squibb and Boehringer Ingelheim. Dr Ansell reports modest Consultant/Advisory Board support from Boehringer Ingelheim, Alere, Bristol-Myers Squibb, Pfizer, Janssen, and Daiichi. Dr Gersh reports modest DSMB/Advisory Board support from Medtronic, Baxter Healthcare Corporation, InspireMD, Cardiovascular Research Foundation, PPD Development, LP, Boston Scientific, and St. Jude. Dr Mahaffey's financial disclosures prior to August 1, 2013, can be viewed at https://www.dcri.org/about-us/conflict-of-interest/Mahaffey-COI_2011-2013.pdf; disclosures after August 1, 2013, can be viewed at http://med.stanford.edu/profiles/kenneth_mahaffey. Dr Hylek reports modest honoraria from Boehringer-Ingelheim and Bayer; modest Consultant/Advisory Board support from Daiichi Sankyo, Ortho-McNeil-Janssen, Johnson & Johnson, Boehringer-Ingelheim, Bristol-Myers Squibb, Roche, and Pfizer. Dr Piccini reports significant Research Grant support from Johnson & Johnson/Janssen Pharmaceuticals; significant Other Research Support from Bayer HealthCare Pharmaceuticals Inc. (formerly Berlex Labs), Boston Scientific Corporation, Johnson & Johnson Pharmaceutical Research & Development; modest Consultant/Advisory Board support from Forest Laboratories, Inc. and Medtronic, Inc.; significant Consultant/Advisory Board support from Johnson & Johnson/Janssen Pharmaceuticals. Dr Peterson reports significant Research Grant support from Eli Lilly & Company, Janssen Pharmaceuticals, Inc., and the American Heart Association; modest Consultant/Advisory Board support from Boehringer Ingelheim, Bristol-Myers Squibb, Janssen Pharmaceuticals, Inc., Pfizer, and Genentech Inc. The other authors report no conflicts.FootnotesCirculation is available at http://circ.ahajournals.org.Correspondence to: Sean D. Pokorney, MD, MBA, Division of Cardiology, Duke University Medical Center, DUMC 3845, Durham, NC 27710. E-mail [email protected]References1. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.Lancet. 2014; 383:955–962. doi: 10.1016/S0140-6736(13)62343-0.CrossrefMedlineGoogle Scholar2. Bohula EA, Giugliano RP, Ruff CT, Kuder JF, Murphy SA, Antman EM, Braunwald E. Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI 48 Trial.Circulation. 2016; 134:24–36. doi: 10.1161/CIRCULATIONAHA.116.022361.LinkGoogle Scholar3. Washam JB, Herzog CA, Beitelshees AL, Cohen MG, Henry TD, Kapur NK, Mega JL, Menon V, Page RL, Newby LK; American Heart Association Clinical Pharmacology Committee of the Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, Council on Functional Genomics and Translational Biology, Council on the Kidney in Cardiovascular Disease, and Council on Quality of Care and Outcomes Research. Pharmacotherapy in chronic kidney disease patients presenting with acute coronary syndrome: a scientific statement from the American Heart Association.Circulation. 2015; 131:1123–1149. doi: 10.1161/CIR.0000000000000183.LinkGoogle Scholar4. Stevens LA, Coresh J, Greene T, Levey AS. Assessing kidney function–measured and estimated glomerular filtration rate.N Engl J Med. 2006; 354:2473–2483. doi: 10.1056/NEJMra054415.CrossrefMedlineGoogle Scholar5. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration):a new equation to estimate glomerular filtration rate.Ann Intern Med. 2009; 150:604–612.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Nabiee M, Dashti-Khavidaki S and Khajeh B (2020) Dose discordance of direct acting oral anticoagulants using different equations for estimating GFR: a literature review, Expert Review of Clinical Pharmacology, 10.1080/17512433.2020.1798759, 13:8, (857-863), Online publication date: 2-Aug-2020. Pokorney S, Peterson E and Piccini J (2017) When Less Is Not More ∗, Journal of the American College of Cardiology, 10.1016/j.jacc.2017.04.045, 69:23, (2791-2793), Online publication date: 1-Jun-2017. Ueberham L, Dagres N, Potpara T, Bollmann A and Hindricks G (2017) Pharmacological and Non-pharmacological Treatments for Stroke Prevention in Patients with Atrial Fibrillation, Advances in Therapy, 10.1007/s12325-017-0616-6, 34:10, (2274-2294), Online publication date: 1-Oct-2017. October 11, 2016Vol 134, Issue 15 Advertisement Article InformationMetrics © 2016 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.116.024333PMID: 27753615 Originally publishedOctober 11, 2016 Keywordsrenal functionanticoagulationatrial fibrillationPDF download Advertisement SubjectsAnticoagulantsAtrial FibrillationHealth ServicesIschemic Stroke
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