Circu- lation 2004;110:975 81. 303. Rogers JG, Butler J, Lansman SL, et al. Chronic mechanical circulatory support for inotrope-dependent heart failure patients who are not trans- plant candidates: results of the INTrEPID Trial. J Am Coll Cardiol 2007; 50:741 7. 304. Slaughter MS, Rogers JG, Milano CA, et al. Advanced heart failure treated with continuous- ow left ventricular assist device. N Engl J Med 2009;361:2241 51. 305. Mehra MR, Kobashigawa J, Starling R, et al. Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates 2006. J Heart Lung Transplant 2006;25:1024 42. 306. Nohria A, Lewis E, Stevenson LW. Medical management of advanced heart failure. JAMA 2002;287:628 40. 307. Metra M, Torp-Pedersen C, Cleland JG, et al. Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET. Eur J Heart Fail 2007;9:901 9. 308. Fonarow GC, Abraham WT, Albert NM, et al. In uence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with heart failure: ndings from the OPTIMIZE-HF program. J Am Coll Cardiol 2008;52:190 9. 309. Butler J, Young JB, Abraham WT, et al. Beta-blocker use and outcomes among hospitalized heart failure patients. J Am Coll Cardiol 2006;47: 2462 9. 310. Maisel AS, Peacock WF, McMullin N, et al. Timing of immunore- active B-type natriuretic peptide levels and treatment delay in acute decompensated heart failure: an ADHERE (Acute Decompensated Heart Failure National Registry) analysis. J Am Coll Cardiol 2008;52: 534 40. 311. Peacock WF, Fonarow GC, Emerman CL, et al. Impact of early initiation of intravenous therapy for acute decompensated heart failure on outcomes in ADHERE. Cardiology 2007;107:44 51. 312. Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated heart failure.


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Ann Intern Med 2004;141:446 53. 338. Phillips CO, Wright SM, Kern DE, et al. Comprehensive discharge planning with postdischarge support for older patients with congestive heart failure: a meta-analysis. JAMA 2004;291:1358 67. 339. Gislason GH, Rasmussen JN, Abildstrom SZ, et al. Persistent use of evidence-based pharmacotherapy in heart failure is associated with improved outcomes. Circulation 2007;116:737 44. 340. Masoudi FA, Rathore SS, Wang Y, et al. National patterns of use and effectiveness of angiotensin-converting enzyme inhibitors in older patients with heart failure and left ventricular systolic dysfunction. Circulation 2004;110:724 31. 341. Braunstein JB, Anderson GF, Gerstenblith G, et al. Noncardiac comor- bidity increases preventable hospitalizations and mortality among Medicare bene ciaries with chronic heart failure. J Am Coll Cardiol 2003;42:1226 33. 342. Windham BG, Bennett RG, Gottlieb S. Care management interventions for older patients with congestive heart failure. Am J Manag Care 2003; 9:447 59. 343. Fonarow GC, Albert NM, Curtis AB, et al. Improving evidence-based care for heart failure in outpatient cardiology practices: primary results of the Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF). Circulation 2010; 122:585 96. 344. Fonarow GC, Abraham WT, Albert NM, et al. Association between performance measures and clinical outcomes for patients hospitalized with heart failure. JAMA 2007;297:61 70. 345. Hernandez AF, Greiner MA, Fonarow GC, et al. Relationship between early physician follow-up and 30-day readmission among Medicare bene ciaries hospitalized for heart failure. JAMA 2010;303: 1716 22. 346. Krumholz HM, Chen YT, Wang Y, et al. Predictors of readmission among elderly survivors of admission with heart failure. Am Heart J 2000;139:72 7. 347. Unpublished data provided by the Of ce of Information Products and Data Analytics-CMS. CMS Administrative Claims Data, Jan 2011 - Dec 2011, from the Chronic Condition Warehouse: 2012. 348.


CMS Administrative Claims Data, Jan 2011 - Dec 2011, from the Chronic Condition Warehouse: 2012. 348. Caracciolo EA, Davis KB, Sopko G, et al. Comparison of surgical and medical group survival in patients with left main coronary artery disease: long-term CASS experience. Circulation 1995;91:2325 34. 349. The VA Coronary Artery Bypass Surgery Cooperative Study Group. Eighteen-year follow-up in the Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery for stable angina. Circulation 1992;86: 121 30. 350. The Veterans Administration Coronary Artery Bypass Surgery Coop- erative Study Group. Eleven-year survival in the Veterans Administra- tion randomized trial of coronary bypass surgery for stable angina. N Engl J Med 1984;311:1333 9. 351. Cleland JG, Calvert M, Freemantle N, et al. The Heart Failure Revas- cularisation Trial (HEART). Eur J Heart Fail 2011;13:227 33. 352. Velazquez EJ, Lee KL, Deja MA, et al. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011;364: 1607 16. 353. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic- valve replacement in high-risk patients. N Engl J Med 2011;364:2187 98. 354. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597 607. 355. Alderman EL, Fisher LD, Litwin P, et al. Results of coronary artery surgery in patients with poor left ventricular function (CASS). Circula- tion 1983;68:785 95. 356. Patel MR, Dehmer GJ, Hirshfeld JW, et al. ACCF/SCAI/STS/AATS/ AHA/ASNC 2009 appropriateness criteria for coronary revasculariza- tion: a report by the American College of Cardiology Foundation Appropriateness Criteria Task Force, Society for Cardiovascular Angi- ography and Interventions, Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, and the American Society of Nuclear Cardiology. J Am Coll Cardiol 2009; 53:530 53. 357.


ACCF/SCAI/STS/AATS/ AHA/ASNC 2009 appropriateness criteria for coronary revasculariza- tion: a report by the American College of Cardiology Foundation Appropriateness Criteria Task Force, Society for Cardiovascular Angi- ography and Interventions, Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, and the American Society of Nuclear Cardiology. J Am Coll Cardiol 2009; 53:530 53. 357. Feldman T, Foster E, Glower DD, et al. Percutaneous repair or surgery for mitral regurgitation. N Engl J Med 2011;364:1395 406. 358. Chan KM, Punjabi PP, Flather M, et al. Coronary artery bypass surgery with or without mitral valve annuloplasty in moderate functional ischemic mitral regurgitation: nal results of the Randomized Ischemic Mitral Evaluation (RIME) trial. Circulation 2012;126:2502 10. 359. Fattouch K, Guccione F, Sampognaro R, et al. POINT: ef cacy of adding mitral valve restrictive annuloplasty to coronary artery bypass grafting in patients with moderate ischemic mitral valve regurgitation: a randomized trial. J Thorac Cardiovasc Surg 2009;138:278 85. 360. Franzen O, van der Heyden J, Baldus S, et al. MitraClip therapy in patients with end-stage systolic heart failure. Eur J Heart Fail 2011;13: 569 76. 361. Jones RH, Velazquez EJ, Michler RE, et al. Coronary bypass surgery with or without surgical ventricular reconstruction. N Engl J Med 2009; 360:1705 17. 362. Inglis SC, Clark RA, McAlister FA, et al. Structured telephone support or telemonitoring programmes for patients with chronic heart failure. Cochrane Database Syst Rev 2010;(8):CD007228. 363. Coleman EA, Boult C. Improving the quality of transitional care for persons with complex care needs. J Am Geriatr Soc 2003;51:556 7. 364. Stewart S, Pearson S, Horowitz JD. Effects of a home-based intervention among patients with congestive heart failure discharged from acute hospital care. Arch Intern Med 1998;158:1067 72. 365. Stewart S, Marley JE, Horowitz JD.


Arch Intern Med 1998;158:1067 72. 365. Stewart S, Marley JE, Horowitz JD. Effects of a multidisciplinary, home- based intervention on unplanned readmissions and survival among patients with chronic congestive heart failure: a randomised controlled study. Lancet 1999;354:1077 83. 366. Sochalski J, Jaarsma T, Krumholz HM, et al. What works in chronic care management: the case of heart failure. Health Aff (Millwood) 2009;28: 179 89. 367. Laramee AS, Levinsky SK, Sargent J, et al. Case management in a heterogeneous congestive heart failure population: a randomized controlled trial. Arch Intern Med 2003;163:809 17. 368. Clark RA, Inglis SC, McAlister FA, et al. Telemonitoring or structured telephone support programmes for patients with chronic heart failure: systematic review and meta-analysis. BMJ 2007;334:942. 369. Chaudhry SI, Phillips CO, Stewart SS, et al. Telemonitoring for patients with chronic heart failure: a systematic review. J Card Fail 2007; 13:56 62. 370. Riegel B, Carlson B, Kopp Z, et al. Effect of a standardized nurse case- management telephone intervention on resource use in patients with chronic heart failure. Arch Intern Med 2002;162:705 12. 371. Riegel B, Carlson B, Glaser D, et al. Randomized controlled trial of telephone case management in Hispanics of Mexican origin with heart failure. J Card Fail 2006;12:211 9. 372. Krumholz HM, Currie PM, Riegel B, et al. A taxonomy for disease management: a scienti c statement from the American Heart Association Disease Management Taxonomy Writing Group. Circulation 2006;114: 1432 45. 373. Faxon DP, Schwamm LH, Pasternak RC, et al. Improving quality of care through disease management: principles and recommendations from the American Heart Association s Expert Panel on Disease Management. Circulation 2004;109:2651 4. 374. Rich MW, Beckham V, Wittenberg C, et al. A multidisciplinary inter- vention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995;333:1190 5. 375.


A multidisciplinary inter- vention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995;333:1190 5. 375. McAlister FA, Lawson FM, Teo KK, et al. A systematic review of randomized trials of disease management programs in heart failure. Am J Med 2001;110:378 84. 376. Riegel B, LePetri B. Heart failure disease management models. In: Moser D, Riegel B, editors. Improving Outcomes in Heart Failure: An JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Interdisciplinary Approach. Gaithersburg, Md: Aspen Publishers; 2001: 267 81. 377. Coleman EA, Mahoney E, Parry C. Assessing the quality of preparation for posthospital care from the patient s perspective: the care transitions measure. Med Care 2005;43:246 55. 378. Lorenz KA, Lynn J, Dy SM, et al. Evidence for improving palliative care at the end of life: a systematic review. Ann Intern Med 2008;148:147 59. 379. Hauptman PJ, Havranek EP. Integrating palliative care into heart failure care. Arch Intern Med 2005;165:374 8. 380. Adler ED, Gold nger JZ, Kalman J, et al. Palliative care in the treatment of advanced heart failure. Circulation 2009;120:2597 606. 381. Qaseem A, Snow V, Shekelle P, et al. Evidence-based interventions to improve the palliative care of pain, dyspnea, and depression at the end of life: a clinical practice guideline from the American College of Physi- cians. Ann Intern Med 2008;148:141 6. 382. Jencks SF, Huff ED, Cuerdon T. Change in the quality of care delivered to Medicare bene ciaries, 1998-1999 to 2000-2001. JAMA 2003;289: 305 12. 383. Bonow RO, Ganiats TG, Beam CT, et al. ACCF/AHA/AMA-PCPI 2011 performance measures for adults with heart failure: a report of the ACCF/AHA Task Force on Performance Measures (Writing Committee to Develop Performance Measures for Heart Failure).


ACCF/AHA/AMA-PCPI 2011 performance measures for adults with heart failure: a report of the ACCF/AHA Task Force on Performance Measures (Writing Committee to Develop Performance Measures for Heart Failure). J Am Coll Cardiol 2012;59:1812 32. Key Words: ACCF/AHA Practice Guidelines - cardio-renal physiology/pathophysiology - congestive heart failure - CV surgery: transplantation, ventricular assistance, cardiomyopathy - epidemiology - health policy and outcome research - heart failure - other heart failure. Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 Appendix 1.


16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 Appendix 1. Author Relationships With Industry and Other Entities (Relevant)d2013 ACCF/AHA Guideline for the Management of Heart Failure Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Clyde W. Yancy, Chair Northwestern UniversitydChief, Division of Cardiology and Magerstadt Professor of Medicine None None None None None None None Mariell Jessup, Vice Chair University of PennsylvaniadProfessor of Medicine None None None  Amgen  Celladon  HeartWare None None 7.4.4 Biykem Bozkurt Michael E. DeBakey VA Medical CenterdThe Mary and Gordon Cain Chair and Professor of Medicine None None None None None None None Javed Butler Emory HealthcaredDirector of Heart Failure Research; Emory University School of MedicinedProfessor of Medicine  Amgen  CardioMEMS  Gambro  Takeda None None None  Amgen  Biotronic  Boston Scientific  CardioMEMS  Cortheray  FoldRx  iOcopsys  Johnson & Johnson  Medtronic  Thoratec  World Heart Donald E. Casey, Jr Clinically Integrated Physician Network, NYU Langone Medical CenterdVice President and Medical Director None None None None None None None Mark H. Drazner University of Texas Southwestern Medical CenterdProfessor, Internal Medicine None None None  HeartWare  Scios/Johnson & Johnsony  Medtronic  Thoratecy Gregg C. Fonarow Director AhmansondUCLA Cardiomyopathy Center; Co-ChiefdUCLA Division of Cardiology  Gambro (formerly CHF Solutions)  Medtronic  Novartisy  Takeda None None  Gambro (formerly CHF Solutions)  Novartisy  Medtronic None 7.1 7.2 (Class IIa) Stephen A. Geraci Quillen College of Medicine/East Tennessee State Universityd Chairman of Internal Medicine None None None None None None None (Continued on the next page) JACC Vol. 62, No. 16, 2013 Yancy et al.


Author Relationships With Industry and Other Entities (Relevant)d2013 ACCF/AHA Guideline for the Management of Heart Failure Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Clyde W. Yancy, Chair Northwestern UniversitydChief, Division of Cardiology and Magerstadt Professor of Medicine None None None None None None None Mariell Jessup, Vice Chair University of PennsylvaniadProfessor of Medicine None None None  Amgen  Celladon  HeartWare None None 7.4.4 Biykem Bozkurt Michael E. DeBakey VA Medical CenterdThe Mary and Gordon Cain Chair and Professor of Medicine None None None None None None None Javed Butler Emory HealthcaredDirector of Heart Failure Research; Emory University School of MedicinedProfessor of Medicine  Amgen  CardioMEMS  Gambro  Takeda None None None  Amgen  Biotronic  Boston Scientific  CardioMEMS  Cortheray  FoldRx  iOcopsys  Johnson & Johnson  Medtronic  Thoratec  World Heart Donald E. Casey, Jr Clinically Integrated Physician Network, NYU Langone Medical CenterdVice President and Medical Director None None None None None None None Mark H. Drazner University of Texas Southwestern Medical CenterdProfessor, Internal Medicine None None None  HeartWare  Scios/Johnson & Johnsony  Medtronic  Thoratecy Gregg C. Fonarow Director AhmansondUCLA Cardiomyopathy Center; Co-ChiefdUCLA Division of Cardiology  Gambro (formerly CHF Solutions)  Medtronic  Novartisy  Takeda None None  Gambro (formerly CHF Solutions)  Novartisy  Medtronic None 7.1 7.2 (Class IIa) Stephen A. Geraci Quillen College of Medicine/East Tennessee State Universityd Chairman of Internal Medicine None None None None None None None (Continued on the next page) JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Appendix 1.


October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Appendix 1. Continued Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Tamara Horwich AhmansondUCLA Cardiomyopathy CenterdAssistant Professor of Medicine, Cardiology None None None None None None None James L. Januzzi Harvard Medical SchooldAssociate Professor of Medicine; Massachusetts General HospitaldDirector, Cardiac Intensive Care Unit  Critical Diagnosticsy  Roche Diagnosticsy None None  Critical Diagnosticsy  Roche Diagnosticsy None None 6.2 Maryl R. Johnson University of Wisconsin Madison, Professor of Medicine, Director Heart Failure and Transplantation None None None None None None None Edward K. Kasper Johns Hopkins Hospitald E. Cowles Andrus Professor in Cardiology, Director, Clinical Cardiology None None None None None None None Wayne C. Levy University of WashingtondProfessor of Medicine, Division of Cardiology  Cardiac Dimensionsy  CardioMEMS  GE/Scios/ Johnson & Johnson  Amarin  Boehringer Ingelheim  GlaxoSmithKline None  Amgeny  HeartWarey  Amgen  Epocrates  GE Healthcare  HeartWare  Thoratec Frederick A. Masoudi University of Colorado, DenverdAssociate Professor of Medicine, Division of Cardiology None None None None None None None Patrick E. McBride University of Wisconsin School of Medicine and Public HealthdProfessor of Medicine and Family Medicine, Associate Dean for Students, Associate Director, Preventive Cardiology None None None None None None None John J.V. McMurray University of Glasgow, Scotland, BHF Glasgow Cardiovascular Research CenterdProfessor of Medical Cardiology None None None  GlaxoSmithKliney  Novartis  Roche (DSMB)  Novartis (PARADIGM PI) 7.2 (Class I and Class III) Judith E. Mitchell SUNY Downstate Medical CenterdDirector, Heart Failure Center; Associate Professor of Medicine None None None None None None None (Continued on the next page) Yancy et al. JACC Vol. 62, No.


McMurray University of Glasgow, Scotland, BHF Glasgow Cardiovascular Research CenterdProfessor of Medical Cardiology None None None  GlaxoSmithKliney  Novartis  Roche (DSMB)  Novartis (PARADIGM PI) 7.2 (Class I and Class III) Judith E. Mitchell SUNY Downstate Medical CenterdDirector, Heart Failure Center; Associate Professor of Medicine None None None None None None None (Continued on the next page) Yancy et al. JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 Appendix 1. Continued Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Pamela N. Peterson University of Colorado, Denver Health Medical CenterdAssociate Professor of Medicine, Division of Cardiology None None None None None None None Barbara Riegel University of Pennsylvania School of NursingdProfessor None None None None None None None Flora Sam Boston University School of Medicine, Whitaker Cardiovascular InstitutedAssociate Professor of Medicine, Division of Cardiology/ Cardiomyopathy Program None None None None None None None Lynne W. Stevenson Brigham and Women s Hospital Cardiovascular DivisiondDirector, Cardiomyopathy and Heart Failure Program None None None  Biosense Webster None None 7.3.4 W.H.


Continued Committee Member Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* Pamela N. Peterson University of Colorado, Denver Health Medical CenterdAssociate Professor of Medicine, Division of Cardiology None None None None None None None Barbara Riegel University of Pennsylvania School of NursingdProfessor None None None None None None None Flora Sam Boston University School of Medicine, Whitaker Cardiovascular InstitutedAssociate Professor of Medicine, Division of Cardiology/ Cardiomyopathy Program None None None None None None None Lynne W. Stevenson Brigham and Women s Hospital Cardiovascular DivisiondDirector, Cardiomyopathy and Heart Failure Program None None None  Biosense Webster None None 7.3.4 W.H. Wilson Tang Cleveland Clinic FoundationdAssociate Professor of Medicine, Research Director for Heart Failure/Transplant  Medtronic  St. Jude Medical None None  Abbotty  FoldRx  Johnson & Johnson  Medtronicy  St. Jude Medicaly None None 6.2 Emily J. Tsai Temple University School of MedicinedAssistant Professor of Medicine, Cardiology None None None None None None None Bruce L. Wilkoff Cleveland ClinicdDirector, Cardiac Pacing and Tachyarrhythmia Devices; Director, Clinical EP Research None None None  Biotronic  Boston Scientific  Medtronic  St. Jude Medical None None 7.2 (Class IIa) This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document. These relationships were reviewed and updated in conjunction with all meetings and/or conference calls of the writing committee during the document development process. The table does not necessarily reflect relationships with industry at the time of publication.


The table does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% of the voting stock or share of the business entity, or ownership of $10,000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year. Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. According to the ACCF/AHA, a person has a relevant relationship IF: a) The relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) The company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) The person or a member of the person s household, has a reasonable potential for financial, professional or other personal gain or loss as a result of the issues/content addressed in the document. *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply. Section numbers pertain to those in the full-text guideline. yIndicates significant relationship.


Section numbers pertain to those in the full-text guideline. yIndicates significant relationship. DSMB indicates Data Safety Monitoring Board; EP, electrophysiology; NYU, New York University; PARADIGM, a Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic Heart Failure and Reduced Ejection Fraction; PI, Principal Investigator; SUNY, State University of New York; UCLA, University of California, Los Angeles; and VA, Veterans Affairs. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Appendix 2.


October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Appendix 2. Reviewer Relationships With Industry and Other Entities (Relevant)d2013 ACCF/AHA Guideline for the Management of Heart Failure Reviewer Representation Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Nancy Albert Official Reviewerd ACCF/AHA Task Force on Practice Guidelines Kaufman Center for Heart FailuredSenior Director of Nursing Research  BG Medicine  Medtronic  Mercky None None None None None Kathleen Grady Official ReviewerdAHA Bluhm Cardiovascular Instituted Administrative Director, Center for Heart Failure None None None None None None Paul Hauptman Official ReviewerdAHA St Louis University School of Medicined Professor of Internal Medicine, Division of Cardiology  BG Medicine  BioControl Medical  Otsuka* None None None  EvaHearty None Hector Ventura Official Reviewerd ACCF Board of Governors Ochsner Clinic Foundationd Director, Section of Cardiomyopathy and Heart Transplantation  Otsuka  Actelion None None None None Mary Norine Walsh Official Reviewerd ACCF Board of Trustees St. Vincent Heart Center of Indianad Medical Director  United Healthcare None None None None None Jun Chiong Organizational ReviewerdACCP Loma Linda UniversitydAssociate Clinical Professor of Medicine None None None None  Otsuka (DSMB) None David DeLurgio Organizational ReviewerdHRS The Emory ClinicdAssociate Professor, Director of EP Laboratory None None None None None None Folashade Omole Organizational ReviewerdAAFP Morehouse School of MedicinedAssociate Professor of Clinical Family Medicine None None None None None None Robert Rich, Jr Organizational ReviewerdAAFP Bladen Medical AssociatesdFamily Practice None None None None None None David Taylor Organizational ReviewerdISHLT Cleveland Clinic, Department of CardiologydProfessor of Medicine None None None None  Biotronixy  Genentechy  HeartWarey  ISHLT  Novartisy  St. Jude s Medicaly None Kimberly Birtcher Content ReviewerdACCF Cardiovascular Team Council University of Houston College of PharmacydClinical Professor None None None None None None Kay Blum Content ReviewerdACCF Cardiovascular Team Council Medstar Southern Maryland Hospital CenterdNurse Practitioner None None None None None None (Continued on the next page) Yancy et al.


JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 Appendix 2.


16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 Appendix 2. Continued Reviewer Representation Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Michael Chan Content Reviewerd ACCF Cardiovascular Team Council Royal Alexandra HospitaldCo-Director, Heart Function Program; University of AlbertadAssociate Clinical Professor of Medicine None None None None  Medtronic None Jane Chen Content Reviewerd ACCF EP Committee Washington University School of MedicinedAssistant Professor of Medicine  Medtronic  St. Jude Medical None None None None None Michael Clark Content Reviewerd ACCF Cardiovascular Team Council North Texas Cardiology and EPdAssociate Professor None  Abbott Pharma None None None None Marco Costa Content Reviewerd ACCF Imaging Council University Hospital for ClevelanddProfessor of Medicine  Abbott Vascular  Boston Scientific  Cardiokinetix*  Medtronic  St. Jude Medical  Daiichi- Sankyo  Eli Lilly  Sanofi None None  Abbott Vascular*  Boston Scientific  Cardiokinetixy  Medtronic*  St. Jude Medical None Anita Deswal Content Reviewer Baylor College of MedicinedAssociate Professor of Medicine None None None  Amgeny  Novartisy None None Steven Dunn Content Reviewerd ACCF Prevention Committee University of Virginia Health SystemdClinical Pharmacy Specialist None None None None None None Andrew Epstein Content Reviewer University of PennsylvaniadProfessor of Medicine  Biotronic  Boehringer Ingelheim  Medtronic  Zoll None None  Biosense Webster*  Boston Scientific*  Cameron Health*  Boston Scientific*  St. Jude Medical* None Justin Ezekowitz Content ReviewerdAHA Mazankowski Alberta Heart InstitutedDirector, Heart Function Clinic  Abbott Labs  AstraZeneca  Pfizer None None  Amgen  Bristol-Myers Squibb None None Gerasimos Filippatos Content Reviewer University of AthensdDepartment of Cardiology None None None None  Corthera  Vifor None Linda Gillam Content Reviewerd ACCF Imaging Council Morristown Medical CenterdProfessor of Cardiology None None None None  Edwards Lifesciencesy None Paul Heidenreich Content Reviewer Stanford VA Palo Alto Medical CenterdAssistant Professor of Medicine None None None  Medtronicy None None Paul Hess Content Reviewerd ACCF EP Committee Duke University School of MedicinedFellow None None None None None None Sharon Ann Hunt Content Reviewer Stanford University Medical CenterdProfessor, Department of Cardiovascular Medicine None None None None None None (Continued on the next page) JACC Vol.


62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Appendix 2.


October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary Appendix 2. Continued Reviewer Representation Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Charles McKay Content Reviewerd ACCF Council on Cardiovascular Care for Older Adults Harbor-UCLA Medical CenterdProfessor of Medicine None None None None None None James McClurken Content Reviewerd ACCF Surgeons Scientific Council Temple University School of Medicined Director of Cardiothoracic Perioperative Services None None None None None None Wayne Miller Content Reviewerd ACCF Heart Failure and Transplant Council Mayo ClinicdProfessor of Medicine None None None None None None Rick Nishimura Content Reviewer Mayo ClinicdProfessor of Medicine None None None None None None Donna Petruccelli Content Reviewerd ACCF Heart Failure and Transplant Council Lehigh Valley Health NetworkdHeart Failure Nurse Practitioner/Clinical Nurse Specialist, Center for Advanced Heart Failure None None None None None None Geetha Raghuveer Content Reviewerd ACCF Board of Governors Children s Mercy HospitaldAssociate Professor of Pediatrics None None None None None None Pasala Ravichandran Content Reviewerd ACCF Surgeons Scientific Council Oregon Health & Science UniversitydAssociate Professor None None None None None None Michael Rich Content Reviewerd ACCF Council on Cardiovascular Care for Older Adults Washington University School of Medicined Professor of Medicine None None None None None None Anitra Romfh Content Reviewerd ACCF Adult Congenital and Pediatric Cardiology Council Children s Hospital BostondClinical Fellow in Pediatrics None None None None None None Andrea Russo Content Reviewerd ACCF Task Force on Appropriate Use Criteria Cooper University HospitaldProfessor of Medicine  Biotronik  Boston Scientific  Cameron Health  Medtronic  St. Jude Medical None None  Cameron Health  Medtronic None None Dipan Shah Content Reviewerd ACCF Imaging Council Methodist DeBakey Heart CenterdDirector None  AstraZeneca*  Lantheus Medical Imaging None None  Astellas Pharma  Siemens Medical Solutions* None Randy Starling Content Reviewer Cleveland Clinic, Department of Cardiovascular Medicined Vice Chairman  Novartis None None None  Biotronik  Medtronic None Karen Stout Content Reviewerd ACCF Adult Congenital and Pediatric Cardiology Council University of Washingtond Director, Adult Congenital Heart Disease Program None None None None None None (Continued on the next page) Yancy et al.


JACC Vol. 62, No. 16, 2013 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary October 15, 2013:1495 539 Appendix 2. Continued Reviewer Representation Employment Consultant Speaker s Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness John Teerlink Content Reviewer San Francisco VA Medical Centerd Professor of Medicine  Amgen*  Anexon  CardioMEMS*  Cytokinetics  Novartis*  Scios/ Johnson & Johnson  St. Jude Medical*  Trevena None None None  Amgen*  Merck  Novartis* None Robert Touchon Content Reviewerd ACCF Prevention Committee Marshall University, Joan C. Edwards School of Medicined Professor of Medicine None None None None None None Hiroyuki Tsutsui Content Reviewer Hokkaido UniversitydProfessor of Medicine  Daiichi-Sankyo*  Novartis*  Pfizer  Takeda* None None None None None Robert Vincent Content Reviewerd ACCF Adult Congenital and Pediatric Cardiology Council Emory University School of Medicined Professor of Pediatrics None None None None  AGA None This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review and determined to be relevant to this document. It does not necessarily reflect relationships with industry at the time of publication. A person is deemed to have a significant interest in a business if the interest represents ownership of 5% of the voting stock or share of the business entity, or ownership of $10,000 of the fair market value of the business entity; or if funds received by the person from the business entity exceed 5% of the person s gross income for the previous year. A relationship is considered to be modest if it is less than significant under the preceding definition. Relationships that exist with no financial benefit are also included for the purpose of transparency.


Relationships that exist with no financial benefit are also included for the purpose of transparency. Relationships in this table are modest unless otherwise noted. Names are listed in alphabetical order within each category of review. According to the ACCF/AHA, a person has a relevant relationship IF: a) The relationship or interest relates to the same or similar subject matter, intellectual property or asset, topic, or issue addressed in the document; or b) The company/entity (with whom the relationship exists) makes a drug, drug class, or device addressed in the document, or makes a competing drug or device addressed in the document; or c) The person or a member of the person s household, has a reasonable potential for financial, professional or other personal gain or loss as a result of the issues/content addressed in the document. *Significant relationship. yNo financial benefit. AAFP indicates American Academy of Family Physicians; ACCF, American College of Cardiology Foundation; ACCP, American College of Chest Physicians AHA, American Heart Association; DSMB, data safety monitoring board; EP, electrophysiology; HRS, Heart Rhythm Society; ISHLT, International Society for Heart and Lung Transplantation; UCLA, University of California, Los Angeles; and VA, Veterans Affairs. JACC Vol. 62, No. 16, 2013 Yancy et al. October 15, 2013:1495 539 2013 ACCF/AHA Heart Failure Guidelines: Executive Summary


KDIGO Clinical Practice Guideline for Lipid Management in CKD: summary of recommendation statements and clinical approach to the patient , Marcello Tonelli2 and the Kidney Disease: Improving Global Outcomes Lipid Guideline Development Work Group Members3 Division of Nephrology, University of Wu rzburg, Wu rzburg, Germany and 2 University of Alberta, Edmonton, AB, Canada The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed clinical practice guidelines on lipid management for all adults and children with chronic kidney disease (CKD). Thirteen recommendations were obtained from the available evidence outlining a three-step management including assessment in all, treatment in many, and follow-up measurements in few. A key element is the recommendation of statin or statin/ezetimibe treatment in adults aged X50 years with estimated glomerular filtration rate (eGFR) o60ml/min per 1.73m2 but not treated with chronic dialysis or kidney transplantation. In dialysis patients, the magnitude of any relative reduction in risk appears to be substantially smaller than in earlier stages of CKD and initiation of statin treatment is not recommended for most prevalent hemodialysis patients. In the past, clinical practice guidelines suggested the use of targets for LDL cholesterol, which require repeated measurements. Treatment escalation with higher doses of statin would be a consequence when LDL cholesterol targets are not met. The KDIGO Work Group did not recommend this strategy because higher doses of statins have not been proven to be safe in the setting of CKD. Since LDL cholesterol levels do not necessarily suggest the need to increase statin doses, follow-up measurement of lipid levels is not recommended.


Since LDL cholesterol levels do not necessarily suggest the need to increase statin doses, follow-up measurement of lipid levels is not recommended. published online 19 February 2014 KEYWORDS: cholesterol; chronic kidney disease; dyslipidemia; evidence- based recommendation; systematic review; triglyceride Kidney Disease: Improving Global Outcomes (KDIGO) developed the clinical practice guidelines on lipid manage- ment in 2013 to inform the management of dyslipidemia and the use of cholesterol-lowering medications in all adults and children with known CKD. All forms of CKD were included (non-dialysis-dependent, dialysis-dependent, and kidney transplant recipients). The KDIGO Lipid Guideline Devel- opment Work Group defined the scope of the guideline, gathered evidence, determined topics for systematic review, and graded the quality of evidence that had been summarized by an evidence review team. Searches of the English-language literature were conducted through August 2011 and supple- mented by targeted searches through June 2013. The final modification of the guidelines was informed by the KDIGO Board of Directors and a public review process involving registered stakeholders. The full guideline including 13 recommendations was released on 7 November 2013 and is available at http: //www.kdigo.org/.1 Here we provide a quick summary of the KDIGO recommendations for lipid-lowering treatment separated into assessment of lipid status and pharmacological choles- terol- and triglyceride (TG)-lowering treatment in children and adults with CKD. GUIDELINE DEVELOPMENT PROCESS, EVIDENCE GRADING, AND STAKEHOLDER AND PUBLIC CONSULTATION The Work Group consisted of a truly international group of kidney specialists, diabetologists, cardiologists, epidemiolo- gists, lipidologists, and a professional evidence review team.


GUIDELINE DEVELOPMENT PROCESS, EVIDENCE GRADING, AND STAKEHOLDER AND PUBLIC CONSULTATION The Work Group consisted of a truly international group of kidney specialists, diabetologists, cardiologists, epidemiolo- gists, lipidologists, and a professional evidence review team. The Work Group formulated the scope of the guideline, and graded evidence on the basis of the GRADE (Grading of Recommendations Assessment, Development and Evalua- The guideline updates the 2003 Kidney Disease Outcomes Quality Initiative (K/DOQI) Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease.3 The evidence review team carried out systematic reviews for six topics of interest. Systematic searches were last conducted in August 2011 and supplemented with additional evidence through June 2013. Further guideline development, evidence synthesis, and writing of the guideline itself was carried out http://www.kidney-international.org review & 2014 International Society of Nephrology Correspondence: Christoph Wanner, Division of Nephrology, University Hospital Wu rzburg, Oberduerrbacherstrasse 6, Wu rzburg 9700, Germany. E-mail: wanner_c@ukw.de Members of the Kidney Disease: Improving Global Outcomes Lipid Guideline Development Work Group were: Alan Cass, Amit X. Garg, Hallvard Holdaas, Alan G. Jardine, Lixin Jiang, Florian Kronenberg, Rulan S. Parekh, Tetsuo Shoji, and Robert J. Walker. Also see the Appendix. by the Work Group. Full details of the guideline development process, topic discussion, and consensus development can be found in the published guideline.1 The draft guideline was reviewed by the KDIGO Board of Directors, and revisions were incorporated before a structured, Internet-based public review process. Feedback from this process was reviewed by the Work Group, and final revisions were incorporated before publication of the guideline. The order of recommendations in the guideline was based on the order used in the 2003 K/DOQI publication, and it presents recommendations on assessment of lipid status before those related to treatment.


The order of recommendations in the guideline was based on the order used in the 2003 K/DOQI publication, and it presents recommendations on assessment of lipid status before those related to treatment. RECOMMENDATIONS RELATING TO PHARMACOLOGICAL CHOLESTEROL-LOWERING TREATMENT IN ADULTS Background To maximize the ratio of benefits to harm, future coronary risk is considered an important potential determinant of the decision to prescribe statin treatment.4 In people without kidney disease, low-density lipoprotein cholesterol (LDL-C) is often used as a proxy for future risk, as LDL-C levels are independently associated with the risk of atherosclerotic events.5 However, the relative risk (RR) reduction associated with statin use is approximately constant across a broad range of baseline LDL-C levels, suggesting that absolute benefit from statin treatment is proportional to baseline coronary risk rather than baseline LDL-C. LDL-C is not suitable for assessing coronary risk in people with CKD: although higher levels of LDL-C are associated with higher risk, dialysis patients with very low levels of LDL-C and total cholesterol are at a very high risk of all-cause and cardiovascular mortality,5 9 likely because of coexisting malnutrition and inflammation.10,11 Among people with CKD but without kidney failure, the excess risk associated with increased LDL-C decreases in parallel with estimated glome- rular filtration rate (eGFR).12 The weaker association between LDL-C and coronary risk among those with lower levels of eGFR (who are at the highest risk of myocardial infarction (MI) and other vascular events) suggest that it should not be used to identify the CKD patients who should receive statin treatment. Future cardiovascular risk is often assessed using the 10-year incidence of coronary death or non-fatal MI, numerically equivalent to the rate of such events per 1000 patient-years.


Future cardiovascular risk is often assessed using the 10-year incidence of coronary death or non-fatal MI, numerically equivalent to the rate of such events per 1000 patient-years. There is debate about the level of future coronary risk that is sufficient to justify statin treatment, but in the Work Group s judgment a rate of coronary death or non-fatal MI that exceed 10 per 1000 patient-years is a reasonable criterion. The rate of coronary death or incident MI among CKD patients aged 450 years (both men and women) is consistently 410 per 1000 patient-years, even in those without diabetes or prior MI. In contrast, the rate of coronary death or incident MI among CKD patients aged p50 years is low in those without diabetes or prior MI (although it is substantially higher than in people with similar characteristics but without CKD). For comparison, the recent 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults suggests an estimated 10-year risk for a first hard atherosclerotic cardiovascular disease event of 47.5% (estimated using the new Pooled Cohort Equations in the CVD-free, non-pregnant US Population 40 to 79 years of age) as an indication to initiate Available evidence argues against the use of LDL-C to identify people with CKD who should receive statin treatment and suggests focusing on two other factors:1 the absolute risk of coronary events and2 the evidence that statin treatment is beneficial. This is the approach taken in the following KDIGO recommendations.


This is the approach taken in the following KDIGO recommendations. Chapter 1 | Assessment of lipid status in adults with CKD Grade 1C 1.1: In adults with newly identified CKD (including those treated with chronic dialysis or kidney transplantation), we recommend evaluation with a lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) Not graded 1.2: In adults with CKD (including those treated with chronic dialysis or kidney transplantation), follow-up measurement of lipid levels is not required for the majority of patients Within each recommendation, the strength of recommendation is indicated as Level 1, Level 2, or Not graded, and the quality of the supporting evidence is shown as A, B, C, or D (see also Supplementary Appendix Tables S1 and S2 online). GRADE criteria were used for grade levels and letters in this guideline (2). Level 1, We recommend . Most patients should receive the recommended course of action. Level 2, We suggest . Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with her or his values and preferences. Not graded was used, typically, to provide guidance based on common sense or where the topic does not allow adequate application of evidence. Grade A quality of evidence is high, and we are confident that the true effect lies close to that of the estimate of the effect. Grade B is moderate, and the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Grade C is low and the true effect may be substantially different from the estimate of the effect. Grade D is very low. The estimate of effect is very uncertain, and often will be far from the truth.


The estimate of effect is very uncertain, and often will be far from the truth. WHY SHOULD WE OBTAIN A FULL LIPID PROFILE IN ALL CKD PATIENTS AT FIRST PRESENTATION? The major factors predisposing to dyslipidemia in people with CKD are lower GFR, the presence of diabetes mellitus, more severe proteinuria, the use of immunosuppressive agents, modality of renal replacement, comorbidity, and nutritional status.14 Initial evaluation of the lipid profile is intended to diagnose severe hypertriglyceridemia and/or hypercholesterolemia while ruling out any underlying secondary causes. Medical conditions that cause secondary dyslipidemias include hypothyroidism, excessive alcohol consumption, nephrotic syndrome, diabetes mellitus, and liver disease. Medications that may lead to dyslipidemias include corticosteroids, diuretics, 13-cis-retinoic acid, review C anticonvulsants, oral contraceptives, highly active antiretro- viral therapy, b-blockers, cyclosporine, and sirolimus. The lipid profile should ideally be measured in patients who have been fasting. However, if this is not feasible, non- fasting values provide useful information as well.15 Fasting specimens will be needed if significant lipid abnormalities are found on initial measurements, especially severe hypertri- glyceridemia.15 17 In the opinion of the Work Group, fasting TG levels above 11.3 mmol/l (1000 mg/dl) or LDL-C levels above 4.9 mmol/l (190 mg/dl) should prompt specialist referral for further evaluation. No direct evidence indicates that measuring lipid status will lead to better clinical outcomes. However, measuring lipid status is noninvasive, inexpensive, and might improve the health of people with secondary dyslipidemia. In the judgment of the Work Group, these considerations justify a strong recommendation despite the low quality of the supporting evidence. WHAT IS THE RATIONALE FOR NOT TAKING FREQUENT FOLLOW-UP MEASUREMENTS OF SERUM LIPIDS?


WHAT IS THE RATIONALE FOR NOT TAKING FREQUENT FOLLOW-UP MEASUREMENTS OF SERUM LIPIDS? Prior guidelines have emphasized treatment escalation to achieve specific LDL-C targets by increasing the dose of statin and/or combination therapy.1,18 Given the lack of data to support this approach,19 the substantial variability in LDL-C measurements,20 and the potential for comedication-related toxicity, this approach is not recommended for people with CKD (see guideline 1.2). As higher risk of future coronary events rather than elevated LDL-C is the primary indication to initiate lipid-lowering treatment in CKD patients, follow- up monitoring of LDL-C (after an initial measurement) will not usually be required for many patients especially given normal variability in LDL-C over time, which reduces the clinical utility of follow-up measurements.21 In the judgment of the Work Group, follow-up measure- ment of lipid levels should be reserved for instances where the results would alter management. Potential reasons to measure the lipid profile in follow-up for people with CKD could include the following: assessment of adherence to statin treatment; change in renal replacement therapy modality or concern about the presence of a new secondary cause of dyslipidemia; or to assess 10-year cardiovascular risk in patients aged o50 years and not currently receiving a statin (because knowledge of LDL-C in this case might suggest that a statin was required see recommendation 2.2). In the judgment of the Work Group, it is unnecessary to measure LDL-C in situations where the results likely would not change management. For example, patients already receiving a statin (or in whom statin treatment is clearly indicated/not indicated based on changes in their cardiovas- cular risk profile or clinical status) would not require follow- up LDL-C measurements because the results would not alter management.


For example, patients already receiving a statin (or in whom statin treatment is clearly indicated/not indicated based on changes in their cardiovas- cular risk profile or clinical status) would not require follow- up LDL-C measurements because the results would not alter management. Similarly, as the link between LDL-C and adverse clinical outcomes is less robust in people with CKD than in people with normal GFR, the value of measuring LDL-C to assess prognosis is unclear. There is no direct evidence that following on-treatment lipid levels will improve clinical outcomes or encourage adherence to statin therapy. However, some patients may prefer to know their lipid levels during follow-up, or may increase their adherence to statin treatment in response to feedback about these levels. In the judgment of the Work Group, these considerations favor an ungraded statement.


In the judgment of the Work Group, these considerations favor an ungraded statement. Chapter 2 | Pharmacological cholesterol-lowering treatment in adults Grade but not treated with chronic dialysis or kidney transplantation (GFR categories G3a G5), we recommend treatment with a statin or statin/ezetimibe combination 1B 2.1.2: In adults aged X50 years with CKD and eGFR X60ml/min (GFR categories G1 G2), we recommend treatment with a statin 2A 2.2: In adults aged 18 49 years with CKD but not treated with chronic dialysis or kidney transplantation, we suggest statin treatment in people with one or more of the following (2A): known coronary disease (myocardial infarction or coronary revascularization) diabetes mellitus prior ischemic stroke estimated 10-year incidence of coronary death or non-fatal myocardial infarction 410% THE SHARP STUDY HAD A LARGE IMPACT ON A STRONG RECOMMENDATION IN GFR CATEGORIES G3A G5 As the absolute risk of future coronary events is consistently 410 per 1000 patient-years in people with non-dialysis- dependent CKD (eGFR o60 ml/min per 1.73 m2 ) who are aged X50 years, knowledge of LDL-C is not required to gauge average coronary risk in these people. Although multivariate prediction instruments might yield more precise estimates of risk for individuals, the Work Group felt that the simplicity of an age-based approach would enhance uptake of the guideline while allowing sufficiently accurate risk prediction. The Study of Heart and Renal Protection (SHARP) indicated that simvastatin/ezetimibe combination therapy reduces the risk of major atherosclerotic events (coronary death, MI, non-hemorrhagic stroke, or any revascularization) compared with placebo in people with GFR categories G3a G5.22 These data are supported by post hoc analyses of randomized trials of statin versus placebo that focus on the subset of participants with CKD at baseline.


The Study of Heart and Renal Protection (SHARP) indicated that simvastatin/ezetimibe combination therapy reduces the risk of major atherosclerotic events (coronary death, MI, non-hemorrhagic stroke, or any revascularization) compared with placebo in people with GFR categories G3a G5.22 These data are supported by post hoc analyses of randomized trials of statin versus placebo that focus on the subset of participants with CKD at baseline. In general, these analyses suggest that statins reduce the relative risk of cardiovascular events to a similar extent among patients with and without CKD, but that the absolute benefit of treatment is larger in CKD patients because of their higher baseline The Work Group concluded that the combination of findings from SHARP, post hoc analyses of trials from the general population (focusing on the subset of partici- pants with CKD), and the large body of evidence from the C review general population trials collectively justify a strong recom- mendation. RESULTS FROM TRIALS IN THE GENERAL POPULATION AND COMORBIDITY HAD IMPACT ON A STRONG RECOMMENDATION IN YOUNGER AGE AND EARLIER STAGES OF CKD Most patients with CKD and eGFR X60 ml/min per 1.73 m2 have albuminuria and slightly reduced or normal eGFR; most of these would have been included but not recognized in trials of statins performed in the general population. The benefit of statin monotherapy appears similar in people with and without albuminuria.24,25 Given these data, the high cardiovascular risk among people with CKD and eGFR categories G1 G2, the large body of evidence supporting the efficacy of statins in the general population, and the lack of justification for a new trial performed specifically in people with CKD and eGFR categories G1 G2, the Work Group judged that a strong recommendation was appropriate.


The benefit of statin monotherapy appears similar in people with and without albuminuria.24,25 Given these data, the high cardiovascular risk among people with CKD and eGFR categories G1 G2, the large body of evidence supporting the efficacy of statins in the general population, and the lack of justification for a new trial performed specifically in people with CKD and eGFR categories G1 G2, the Work Group judged that a strong recommendation was appropriate. Chapter 2 | continued: Pharmacological cholesterol-lowering treatment in adults Grade 2A 2.3.1: In adults with dialysis-dependent CKD, we suggest that statins or statin/ezetimibe combination not be initiated 2C 2.3.2: In patients already receiving statins or statin/ezetimibe combination at the time of dialysis initiation, we suggest that these agents be continued 2A 2.4: In adult kidney transplant recipients, we suggest treatment with a statin WHY DID THE WORK GROUP NOT RECOMMEND INITIATION OF STATIN TREATMENT IN DIALYSIS PATIENTS? Three large trials22,26,27 have failed to show a conclusive benefit of statin treatment (alone or in combination) among prevalent dialysis patients raising the hypo- thesis that inadequate statistical power was responsible for the apparent lack of benefit. Nonetheless, it is clear that even if statins do prevent cardiovascular events in prevalent dialysis patients, the magnitude of any relative reduction in risk is substantially smaller than in earlier stages of CKD.23 Therefore, in the judgment of the Work Group, initiation of statin treatment is not recommended for most prevalent hemodialysis patients. However, patients might decide to receive statin treatment if they are interested in a relatively uncertain and small reduction in cardiovascular events. As high LDL-C might increase the likelihood of benefit from statin in a dialysis patient,28 patients who meet this criterion may be more interested in receiving statin treatment, recognizing that the benefit remains speculative.


As high LDL-C might increase the likelihood of benefit from statin in a dialysis patient,28 patients who meet this criterion may be more interested in receiving statin treatment, recognizing that the benefit remains speculative. Other factors that might influence a patient s decision to receive statin treatment could include a recent cardiovascular event (MI or stroke) or longer anticipated life expectancy (both of which would favor treatment), and more severe comorbidity or higher current medication burden (both of which would favor lack of treatment). WHY SHOULD STATIN TREATMENT NOT BE STOPPED WHEN THE PATIENT NEW ON DIALYSIS HAS RECEIVED TREATMENT IN EARLIER STAGES OF CKD? Available evidence does not directly address whether statins should be discontinued in incident dialysis patients, who may be systematically different from those who are already prevalent on dialysis (such as those included in the major trials of lipid-lowering treatment in dialysis patients). However, 2141 (34%) of SHARP patients without kidney failure at baseline commenced dialysis during the trial and were considered as non-dialysis patients; overall benefit was observed in this latter group.22 The Work Group judged that it is reasonable to continue statins in patients who are already receiving them at the time of dialysis initiation, recognizing that they may lead to less clinical benefit than in patients without kidney failure. Physicians should consider perio- dically reviewing the clinical status of dialysis patients and revisiting the decision to prescribe statins as required. As there is no direct evidence that statin treatment improves cardiovascular outcomes in patients who require dialysis treatment, this is a weak recommendation.


As there is no direct evidence that statin treatment improves cardiovascular outcomes in patients who require dialysis treatment, this is a weak recommendation. Disconti- nuing statin or statin/ezetimibe treatment is reasonable in patients who place a relatively lower value on a small potential relative reduction in vascular events, and a relatively higher value on the risks of polypharmacy, drug drug interactions, and drug toxicity. SHOULD WE TREAT PATIENTS WITH A STATIN AFTER KIDNEY TRANSPLANTATION? The risk of future cardiovascular events in kidney transplant recipients is substantially elevated compared with people without CKD: the rate of cardiovascular death or non-fatal MI is approximately 21.5 per 1000 patient-years.29 The Assessment of LEscol in Renal Transplantation (ALERT) trial showed that fluvastatin (40 80 mg per day) nonsignificantly reduces the risk of coronary death or non-fatal MI, compared with placebo (RR: 0.83; 95% confidence interval: 0.64 1.06). However, fluvastatin led to a significant 35% relative reduction in the risk of cardiac death or definite non-fatal MI (hazard ratio: 0.65; 95% confidence interval: 0.48 0.88)29 in an unblinded extension study. A significant reduction in the original primary outcome was found after 6.7 years of follow-up. The Work Group judged that the apparent benefits observed in ALERT are consistent with the effects of statins in the general population, suggesting that statins will improve cardiovascular outcomes in kidney transplant recipients. However, the lack of statistical significance in the primary analysis and the fact that only one randomized trial was available both favor a weak recommendation.


However, the lack of statistical significance in the primary analysis and the fact that only one randomized trial was available both favor a weak recommendation. review C Chapters 3 and 4 | Assessment of lipid status and pharmacological cholesterol treatment in children with CKD Grade 1C 3.1: In children with newly identified CKD (including those treated with chronic dialysis or kidney transplantation), we recommend evaluation with a lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides) Not graded 3.2: In children with CKD (including those treated with chronic dialysis or kidney transplantation), we suggest annual follow-up measurement of fasting lipid levels 2C 4.1: In children o18 years of age with CKD (including those treated with chronic dialysis or kidney transplantation), we suggest that statins or statin/ezetimibe combination not be initiated THE ATHEROSCLEROTIC PROCESS BEGINS IN CHILDHOOD Many studies document the prevalence of dyslipidemia among children with CKD and end stage renal disease.30,31 As in adults, the pattern of dyslipidemias in children with CKD is greatly influenced by the underlying pathogenesis and duration of CKD, severity of proteinuria, and treatment.30,31 In children or adolescents with CKD, the relationship between dyslipidemias and subsequent atherosclerotic clinical events is not known owing to short follow-up in observa- tional studies or clinical trials. The Pathobiological Determi- nants of Atherosclerosis in Youth (PDAY) study shows, in adolescents with normal kidney function, that atherosclerosis begins in childhood.32 This atherosclerotic process is likely accelerated in nephrotic syndrome, proteinuric states, and chronic kidney disease (CKD) owing to abnormal lipid metabolism and other atherogenic risk factors. The frequency of lipid abnormalities suggests that clinicians should measure lipid levels at baseline in children with CKD to screen for underlying secondary causes of dyslipidemia.


The frequency of lipid abnormalities suggests that clinicians should measure lipid levels at baseline in children with CKD to screen for underlying secondary causes of dyslipidemia. Children with CKD (and their families) place a high value on this potential benefit and are less concerned about the possibility of adverse events or inconvenience associated with baseline measurement of lipid levels. In the judgment of the Work Group, these considerations justify a strong recom- mendation despite the low quality of the available evidence. Children with very severely increased hypertriglyceridemia (411.3 mmol/l (41000 mg/dl)) should be referred to a pediatric lipid specialist for management and to rule out familial hypertriglyceridemia or rare, inherited disorders such as lipoprotein lipase deficiency or apolipoprotein C-II deficiency. UNLIKE ADULTS, GROWTH AND DEVELOPMENT IN CHILDREN HAVE THE POTENTIAL TO INFLUENCE LIPID LEVELS OVER TIME The ideal frequency of follow-up for fasting levels of LDL-C, HDL-C, and serum TGs is unknown. More frequent (or less frequent) follow-up measurements may be appropriate based on the clinical status of the patient, and the potential for such follow-up measurements to influence manage- ment.33 Possible changes in management in response to such measurements are likely. LACK OF EVIDENCE FOR BENEFIT AND SAFETY PRECLUDES STATIN TREATMENT IN CHILDREN OR ADOLESCENTS Clinical trials of dyslipidemias in children are limited given the rapid transitions from CKD to dialysis and/or transplant, which complicates trial design, recruitment, and analyses. Four randomized trials have examined drug treatment of dyslipide- mia primarily in children with nephrotic syndrome, but no trials have studied clinically relevant outcomes.34 37 These trials demonstrate that statins lower LDL-C over 7 months to 5 years, but no dose escalation has been carried out. There have been 13 placebo-controlled trials of statins in 1683 children with dyslipidemias and normal kidney function.


There have been 13 placebo-controlled trials of statins in 1683 children with dyslipidemias and normal kidney function. This recommendation does not apply to children with severely elevated LDL-C, and therapeutic lifestyle changes should be adopted among all children with CKD. As for all weak recommendations, practitioners should consider the clinical circumstances, patient s age, and preferences when considering an individual patient and his lifetime risk for atherosclerotic cardiovascular disease events with potential exposure to high LCL-C. Treatment strategies based on lifetime risk are problematic because of the lack of data on the long-term follow-up of randomized clinical trials 415 years in the general population, the safety, and event reduction when statins are used for periods 410 years, especially in individuals o40 years of age. Chapters 5 and 6 | Triglyceride-lowering treatment in adults and in children Grade 2D 5.1: In adults with CKD (including those treated with chronic dialysis or kidney transplantation) and hypertriglyceridemia, we suggest that therapeutic lifestyle changes be advised 2D 6.1: In children with CKD (including those treated with chronic dialysis or kidney transplantation) and hypertriglyceridemia, we suggest that therapeutic lifestyle changes be advised NO RECOMMENDATION FOR PHARMACOLOGICAL TREATMENT OF HIGH TGS IN ADULTS COULD BE MADE A meta-analysis of data from 18 randomized trials involving 45,058 participants drawn from the general population (i.e., not specific to CKD) demonstrated a modest 10% relative risk reduction in major cardiovascular events and a 13% relative risk reduction in coronary events for fibrate therapy.38 Too few participants with eGFR o60 ml/min per 1.73 m2 were included in either FIELD (The Fenofibrate Intervention and Event Lowering in Diabetes) or ACCORD-Lipid (Action to Control Cardiovascular Risk in Diabetes-Lipid) to provide reliable information on either the safety or efficacy of fenofibrate in this group.


, not specific to CKD) demonstrated a modest 10% relative risk reduction in major cardiovascular events and a 13% relative risk reduction in coronary events for fibrate therapy.38 Too few participants with eGFR o60 ml/min per 1.73 m2 were included in either FIELD (The Fenofibrate Intervention and Event Lowering in Diabetes) or ACCORD-Lipid (Action to Control Cardiovascular Risk in Diabetes-Lipid) to provide reliable information on either the safety or efficacy of fenofibrate in this group. Allocation to fenofibrate in the FIELD study was associated with an increased risk of doubling of plasma creatinine, which cannot simply be explained by the small step-rise in creatinine due to fenofibrate. A recent large observational study in patients aged 466 years demonstrated a clear association between new C review prescriptions for fibric acid derivatives and increased serum creatinine levels, as well as a small increase in the risk of hospitalization and nephrologist consultation.39 These findings contribute to the uncertainty that fibric acid derivatives would yield net clinical benefit in people with CKD. For these reasons, the use of fibric acid derivatives to reduce cardiovascular risk is not recommended in patients with CKD. Fibric acid derivatives could be considered for the rare patients with CKD and markedly elevated fasting levels of serum TGs (411.3 mmol/l (41000 mg/dl)). If such therapy is prescribed, fibric acid derivatives must be dose-adjusted for kidney function. Concomitant therapy with both a fibric acid derivative and a statin is not recommended in patients with CKD owing to the potential for toxicity. Non-pharmacological treatment of high TGs (4500 mg/ dl; 5.65 mmol/l) includes therapeutic lifestyle changes such as dietary modification, weight reduction, increased physical activity, reducing alcohol intake, and treatment of hypergly- cemia (if present).


Non-pharmacological treatment of high TGs (4500 mg/ dl; 5.65 mmol/l) includes therapeutic lifestyle changes such as dietary modification, weight reduction, increased physical activity, reducing alcohol intake, and treatment of hypergly- cemia (if present). Evidence that lifestyle changes will reduce serum TGs in patients with CKD is weak, but the elements of lifestyle changes are unlikely to lead to harm and may improve general health. TREATMENT FOR HYPERTRIGLYCERIDEMIA IN CHILDREN AND ADOLESCENTS SHOULD FOCUS ON SEVERE CASES As for adults, the evidence that lifestyle changes will reduce serum triglyceride levels and/or improve clinical outcomes is weak. Nonetheless, it is reasonable to advise children with high fasting levels of serum TGs (45.65 mmol/l (4500 mg/dl)) to adopt lifestyle changes, but dietary modi- fication should be used judiciously, if at all, in children who are malnourished. The safety and efficacy of lowering TGs with fibrates and niacin have not been established in adolescents; fish oil appears to lower serum TGs after as little as 12 weeks of therapy,40 43 but the longer-term benefits, harms, and tolerability of such treatment is unclear. DISCLOSURE MT, Advisor/Consultant: Merck (honoraria donated to charity). CW, Speaker: Astellas-Pfizer (Japan); Merck & Merck Sharp Dohme. ACKNOWLEDGMENTS We thank the KDIGO cochairs Bertram L. Kasiske and David C. Wheeler; the evidence review team (Ashish Upadhyay, Ethan Balk, Amy Earley, Shana Haynes, Jenny Lamont, Michael Cheung); and all those who provided feedback during the public review of the draft guideline. MT was supported by an AHFMR Population Health Scholar award and a Government of Canada Research Chair in the optimal care of people with CKD. SUPPLEMENTARY MATERIAL Table S1. GRADE Criteria Used for Grade Levels in the KDIGO Lipid Guideline. Table S2. GRADE Criteria Used for Letter Grades in the KDIGO Lipid Guideline.


GRADE Criteria Used for Letter Grades in the KDIGO Lipid Guideline. Supplementary material is linked to the online version of the paper at http://www.nature.com/ki REFERENCES 1. Kidney Disease: Improving Global Outcomes (KDIGO) Lipid Work Group. KDIGO Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease. Kidney Int Suppl 2013; 3: 259 305. 2. Uhlig K, Macleod A, Craig J et al. Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006; 70: 2058 2065. 3. National Kidney Foundation. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis 2003; 41: S1 92. 4. Grundy SM. Diabetes and coronary risk equivalency: what does it mean? Diabetes Care 2006; 29: 457 460. 5. Lewington S, Whitlock G, Clarke R et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet 2007; 370: 1829 1839. 6. Chiang CK, Ho TI, Hsu SP et al. Low-density lipoprotein cholesterol: association with mortality and hospitalization in hemodialysis patients. Blood Purif 2005; 23: 134 140. 7. Coresh J, Longenecker JC, Miller ER 3rd et al. Epidemiology of cardiovascular risk factors in chronic renal disease. J Am Soc Nephrol 1998; 9(Suppl): S24 S30. 8. Iseki K, Yamazato M, Tozawa M et al. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int 2002; 61: 1887 1893. 9. Lowrie EG, Lew NL. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 1990; 15: 458 482. 10. Krane V, Winkler K, Drechsler C et al.


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N Engl J Med 2005; 353: 238 248. 27. Fellstrom BC, Jardine AG, Schmieder RE et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009; 360: 1395 1407. 28. Marz W, Genser B, Drechsler C et al. Atorvastatin and low-density lipoprotein cholesterol in type 2 diabetes mellitus patients on hemodialysis. Clin J Am Soc Nephrol 2011; 6: 1316 1325. 29. Holdaas H, Fellstrom B, Jardine AG et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003; 361: 2024 2031. 30. Saland JM, Ginsberg H, Fisher EA. Dyslipidemia in pediatric renal disease: epidemiology, pathophysiology, and management. Curr Opin Pediatr 2002; 14: 197 204. 31. Saland JM, Ginsberg HN. Lipoprotein metabolism in chronic renal insufficiency. Pediatr Nephrol 2007; 22: 1095 1112. 32. Strong JP, Malcom GT, McMahan CA et al. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA 1999; 281: 727 735. 33. National Kidney Foundation. KDOQI Clinical Practice Guideline for Nutrition in Children with CKD: 2008 update. Am J Kidney Dis 2009; 53: S1 124. 34. Coleman JE, Watson AR. Hyperlipidaemia, diet and simvastatin therapy in steroid-resistant nephrotic syndrome of childhood. Pediatr Nephrol 1996; 10: 171 174. 35. Garcia-de-la-Puente S, Arredondo-Garcia JL, Gutierrez-Castrellon P et al. Efficacy of simvastatin in children with hyperlipidemia secondary to kidney disorders. Pediatr Nephrol 2009; 24: 1205 1210. 36. Sanjad SA, al-Abbad A, al-Shorafa S. Management of hyperlipidemia in children with refractory nephrotic syndrome: the effect of statin therapy. J Pediatr 1997; 130: 470 474. 37. Yoshimura N, Oka T, Okamoto M et al. The effects of pravastatin on hyperlipidemia in renal transplant recipients. Transplantation 1992; 53: 94 99. 38.


The effects of pravastatin on hyperlipidemia in renal transplant recipients. Transplantation 1992; 53: 94 99. 38. Jun M, Foote C, Lv J et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet 2010; 375: 1875 1884. 39. Zhao YY, Weir MA, Manno M et al. New fibrate use and acute renal outcomes in elderly adults a population-based study. Ann Intern Med 2012; 156: 560 569. 40. Cerkauskiene R, Kaminskas A, Kaltenis P et al. Influence of omega-3 fatty acids on lipid metabolism in children with steroid sensitive nephritic syndrome]. Medicina 2003; 39(Suppl 1): 82 87. 41. Chongviriyaphan N, Tapaneya-Olarn C, Suthutvoravut U et al. Effects of tuna fish oil on hyperlipidemia and proteinuria in childhood nephritic syndrome. J Med Assoc Thai 1999; 82(Suppl 1): S122 S128. 42. Goren A, Stankiewicz H, Goldstein R et al. Fish oil treatment of hyperlipidemia in children and adolescents receiving renal replacement therapy. Pediatrics 1991; 88: 265 268. 43. Hogg RJ, Lee J, Nardelli N et al. Clinical trial to evaluate omega-3 fatty acids and alternate day prednisone in patients with IgA nephropathy: report from the Southwest Pediatric Nephrology Study Group. Clin J Am Soc Nephrol 2006; 1: 467 474. SUMMARY OF RECOMMENDATION STATEMENTS Chapter 1: ASSESSMENT OF LIPID STATUS IN ADULTS WITH CKD 1.1: In adults with newly identified CKD (including those treated with chronic dialysis or kidney transplantation), we recommend evaluation with a lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides). (1C) 1.2: In adults with CKD (including those treated with chronic dialysis or kidney transplantation), follow-up measurement of lipid levels is not required for the majority of patients.


(1C) 1.2: In adults with CKD (including those treated with chronic dialysis or kidney transplantation), follow-up measurement of lipid levels is not required for the majority of patients. (Not Graded) CHAPTER 2: PHARMACOLOGICAL CHOLESTEROL- LOWERING TREATMENT IN ADULTS 2.1.1: In adults aged X50 years with eGFR o60 ml/min but not treated with chronic dialysis or kidney transplantation (GFR categories G3a G5), we recommend treatment with a statin or statin/ezetimibe combination. (1A) 2.1.2: In adults aged X50 years with CKD and eGFR (GFR categories G1 G2), we recom- mend treatment with a statin. (1B) 2.2: In adults aged 18-49 years with CKD but not treated with chronic dialysis or kidney transplantation, we suggest statin treatment in people with one or more of the following (2A):  known coronary disease (myocardial infarction or coronary revascularization)  diabetes mellitus  prior ischemic stroke  estimated 10-year incidence of coronary death or non-fatal myocardial infarction 410%. 2.3.1: In adults with dialysis-dependent CKD, we suggest that statins or statin/ezetimibe combination not be 2.3.2: In patients already receiving statins or statin/ ezetimibe combination at the time of dialysis initiation, we suggest that these agents be continued. (2C) 2.4: In adult kidney transplant recipients, we suggest treatment with a statin. (2B) CHAPTER 3: ASSESSMENT OF LIPID STATUS IN CHILDREN WITH CKD 3.1: In children with newly identified CKD (including those treated with chronic dialysis or kidney transplantation), we recommend evaluation with a lipid profile (total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides). (1C) 3.2: In children with CKD (including those treated with chronic dialysis or kidney transplantation), we suggest annual follow-up measurement of fasting lipid levels.


(1C) 3.2: In children with CKD (including those treated with chronic dialysis or kidney transplantation), we suggest annual follow-up measurement of fasting lipid levels. (Not Graded) CHAPTER 4: PHARMACOLOGICAL CHOLESTEROL- LOWERING TREATMENT IN CHILDREN 4.1: In children less than 18 years of age with CKD (including those treated with chronic dialysis or kidney transplantation), we suggest that statins or statin/ezetimibe combination not be initiated. (2C) CHAPTER 5: TRIGLYCERIDE-LOWERING TREATMENT IN ADULTS 5.1: In adults with CKD (including those treated with chronic dialysis or kidney transplantation) and hypertriglyceridemia, we suggest that therapeutic lifestyle changes be advised. (2D) CHAPTER 6: TRIGLYCERIDE-LOWERING TREATMENT IN CHILDREN 6.1: In children with CKD (including those treated with chronic dialysis or kidney transplantation) and hypertrigly- ceridemia, we suggest that therapeutic lifestyle changes be C review


CHEST Supplement www.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e531S ANTITHROMBOTICTHERAPY AND PREVENTION OFTHROMBOSIS, 9TH ED: ACCP GUIDELINES Background: The risk of stroke varies considerably across different groups of patients with atrial brillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical ben- e t for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. Methods: We used the methods described in the Methodology for the Development of Antithrom- botic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Preven- tion of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. Results: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at inter- mediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabiga- tran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of 2).


Conclusions: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach. Abbreviations: AAD5antiarrythmic drug; ACS5acute coronary syndrome; ACTIVE5Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events; AF5atrial brillation; AFASAK5Atrial Fibrillation Aspirin and Anticoagulation; AFFIRM5Atrial Fibrillation Follow-up Investigation of Rhythm Management; CHADS2 5congestive heart failure, hypertension, age 75 years, diabetes mellitus, prior stroke or transient ischemic attack; CHA2DS2- VASc5congestive heart failure (or left ventricular systolic dysfunction), hypertension, age 75 years, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, age 65 to 74 years, female sex; EAFT 5 European Atrial Fibrillation Trial; ESPS5European Stroke Prevention Study; INR5international normalized ratio; LAA5left atrial appendage; MI 5 myocardial infarction; PAF 5 paroxysmal atrial brillation; RCT 5 randomized controlled trial; RE-LY5Randomized Evaluation of Long-Term Anticoagulation Therapy; SPAF5Stroke Prevention in Atrial Fibrilla- tion; TEE5transesophageal echocardiography; TIA5transient ischemic attack; VKA5vitamin K antagonist Antithrombotic Therapy for Atrial Fibrillation Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines John J. You, MD; Daniel E. Singer, MD; Patricia A. Howard, PharmD; Deirdre A. Lane, PhD; Mark H. Eckman, MD; Margaret C. Fang, MD, MPH; Elaine M. Hylek, MD, MPH; Sam Schulman, MD, PhD; Alan S. Go, MD; Michael Hughes, PhD; Frederick A. Spencer, MD; Warren J. Manning, MD; Jonathan L. Halperin, MD; and Gregory Y. H. Lip, MD e532S Antithrombotic Therapy for Atrial Fibrillation oral anticoagulation (Grade 2B) or combination therapy with aspirin and clopidogrel (Grade 2B).


Lane, PhD; Mark H. Eckman, MD; Margaret C. Fang, MD, MPH; Elaine M. Hylek, MD, MPH; Sam Schulman, MD, PhD; Alan S. Go, MD; Michael Hughes, PhD; Frederick A. Spencer, MD; Warren J. Manning, MD; Jonathan L. Halperin, MD; and Gregory Y. H. Lip, MD e532S Antithrombotic Therapy for Atrial Fibrillation oral anticoagulation (Grade 2B) or combination therapy with aspirin and clopidogrel (Grade 2B). Remarks: Patients who place an exceptionally high value on stroke reduction and a low value on avoiding bleeding and the burden associated with antithrom- botic therapy are likely to choose antithrombotic therapy rather than no antithrombotic therapy. Other factors that may in uence the choices above are a consideration of patient-speci c bleeding risk and the presence of additional risk factors for stroke, including age 65 to 74 years and female gender, which have been more consistently validated, and vascular disease, which has been less well validated (see section 2.1.12). The presence of multiple non- CHADS2 risk factors for stroke may favor oral anti- coagulation therapy. 2.1.9. For patients with AF, including those with paroxysmal AF, who are at intermediate risk of stroke (eg, CHADS2 score 1), we recommend oral anticoagulation rather than no therapy (Grade 1B). We suggest oral anticoagulation rather than aspirin (75 mg to 325 mg once daily) (Grade 2B) or combination therapy with aspirin and clopidogrel (Grade 2B). For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than con- cerns about major bleeding), we suggest com- bination therapy with aspirin and clopidogrel rather than aspirin (75 mg to 325 mg once daily) (Grade 2B).


For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than con- cerns about major bleeding), we suggest com- bination therapy with aspirin and clopidogrel rather than aspirin (75 mg to 325 mg once daily) (Grade 2B). Remarks: Patients who place an exceptionally high value on stroke reduction and a low value on avoiding bleeding and the burden associated with anticoagu- lant therapy are likely to choose oral anticoagulation rather than antiplatelet therapy. Other factors that may in uence the choice among antithrombotic ther- apies are a consideration of bleeding risk and the presence of additional risk factors for stroke, includ- ing age 65 to 74 years and female gender, which have been more consistently validated, and vascular disease, which has been less well validated (see sec- tion 2.1.12). The presence of multiple additional non-CHADS2 risk factors for stroke may favor oral anticoagulation therapy. 2.1.10. For patients with AF, including those with paroxysmal AF, who are at high risk of stroke (eg, CHADS2 score 2), we recommend oral anticoagulation rather than no therapy (Grade 1A), aspirin (75 mg to 325 mg once daily) (Grade 1B), or combination therapy with aspirin and clopidogrel (Grade 1B). For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns Revision accepted August 31, 2011.


For patients who are unsuitable for or choose not to take an oral anticoagulant (for reasons other than concerns Revision accepted August 31, 2011. Af liations: From the Department of Medicine (Drs You, Schulman, and Spencer) and Department of Clinical Epidemi- ology and Biostatistics (Dr You), McMaster University, Hamilton, ON, Canada; Department of Medicine (Dr Singer), Harvard Medical School, and Clinical Epidemiology Unit (Dr Singer), General Medicine Division, Massachusetts General Hospital, Boston, MA; School of Pharmacy (Dr Howard), University of Kansas Medical Center, Kansas City, KS; University of Birmingham Centre for Cardiovascular Sciences (Drs Lane and Lip), City Hospital, Birmingham, England; Department of Clinical Medi- cine (Dr Eckman), Division of General Internal Medicine and Center for Clinical Effectiveness, University of Cincinnati, Cin- cinnati, OH; Department of Medicine (Dr Fang), Division of Hospital Medicine, University of California, San Francisco, San Francisco, CA; Boston University Medical Center Research Unit (Dr Hylek), Section of General Internal Medicine, Boston, MA; Comprehensive Clinical Research Unit (Dr Go), Division of Research, Kaiser Permanente Northern California, Oakland, CA; Decision Resources Inc (Dr Hughes), London, England; Sec- tion of Non-invasive Cardiac Imaging (Dr Manning), Beth Israel Deaconess Medical Center, Boston, MA; and The Cardiovas- cular Institute (Dr Halperin), Mount Sinai Medical Center, New York, NY. Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educa- tional grants was also provided by Bristol-Myers Squibb; P zer, Inc; Canyon Pharmaceuticals; and sano -aventis US.


Support in the form of educa- tional grants was also provided by Bristol-Myers Squibb; P zer, Inc; Canyon Pharmaceuticals; and sano -aventis US. Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S. Correspondence to: Gregory Y. H. Lip, MD, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, England; e-mail: g.y.h.lip@bham.ac.uk 2012 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). Summary of Recommendations Note on Shaded Text: Throughout this guideline, shading is used within the summary of recommenda- tions sections to indicate recommendations that are newly added or have been changed since the publica- tion of Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence- Based Clinical Practice Guidelines (8th Edition). Recommendations that remain unchanged are not shaded. 2.1.8. For patients with AF, including those with paroxysmal AF, who are at low risk of stroke (eg, CHADS2 [congestive heart failure, hyper- tension, age 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score 0), we suggest no therapy rather than antithrom- botic therapy (Grade 2B). For patients who do choose antithrombotic therapy, we suggest aspi- rin (75 mg to 325 mg once daily) rather than www.chestpubs.org CHEST / 141 / 2 / FEBRUARY, 2012 SUPPLEMENT e533S For patients with AF at low to intermediate risk of stroke (eg, CHADS2 score of 0 or 1) during the rst 12 months after placement of an intracoronary stent (bare metal or drug eluting), we suggest dual antiplatelet ther- apy rather than triple therapy (Grade 2C).