ACC indicates American College of Cardiology; AHA, American Heart Association; EP, Electrophysiology; HRS, Heart Rhythm Society; IMPROVE-HF, Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting; PI, principal investigator; SUNY, State University of New York; and UT, University of Texas. Appendix 1. Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* CLINICAL STATEMENTS AND GUIDELINES Appendix 2.


Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals by Section* CLINICAL STATEMENTS AND GUIDELINES Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive) 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death (July 2017) Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Salary Expert Witness Alfred E. Buxton Content Reviewer Professor of Medicine Harvard Medical School Beth Israel Deaconess Medical Center None None None NHLBI (DSMB) Medtronic Biosense Webster None None Andrew E. Epstein Content Reviewer Professor of Medicine Cardiovascular Division University of Pennsylvania Chief of Cardiology Section Philadelphia VA Medical Center Zoll* None None Biotronik* Boston Scientific* Boston Scientific (DSMB)* Medtronic* Medtronic (DSMB) St Jude Medical/ Abbott* St Jude Medical/ Abbott (DSMB)* None None Defendant, Amiodarone pulmonary Defendant, Appropriateness of pacemaker implantation, Brian Olshansky Content Reviewer Adjunct Professor of Medicine Des Moines University Professor Emeritus University of Iowa Boehringer Ingleheim Lundbeck Inc* On-X/Cryolife Lundbeck Inc* On-X/Cryolife None Amarin (DSMB)* None None Plaintiff, Long QT sudden Bulent Gorenek Content Reviewer ACC EP Council None None None None None None None Charles I. Berul Content Reviewer Division Chief of Pediatric Cardiology Children s National Medical Center None None None None Circulation* None None Darren Sudman Content Reviewer Executive Director Simon s Fund None None None None None None None George J. Klein Content Reviewer Chief of Cardiology London Health Sciences Center Biotronik Boston Scientific Medtronic* None None None None None None Glenn N. Levine Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines Professor of Medicine Baylor College of Medicine Director Cardiac Care Unit Michael E. DeBakey Medical Center None None None None None None Defendant, Catheterization Laboratory Procedure, Defendant, Out of hospital Gurusher S. Panjrath Content Reviewer ACC Heart Failure and Transplant Council Director Heart Failure and Mechanical Support Program George Washington University Amgen Inc.* None None None BEAT-HF ENDEAVOUR None None James P. Daubert Official Reviewer AHA Duke University Medical Center Biosense Webster Boston Scientific CardioFocus Gilead Heart Metabolics Medtronic* St. Jude Medical Zoll None None ARCA biopharma Biosense Webster* Boston Scientific* Gilead* Gilead (DSMB) Medtronic* NHLBI* NHLBI (DSMB) Northwestern University St. Jude Medical (DSMB) VytronUS (DSMB) Biosense* Biotronik* Boston Scientific* Gilead Scienes, Inc.* Medtronic* St. Jude Medical* ACC None James Tisdale Content Reviewer ACC EP Council Professor College of Pharmacy Purdue University Adjunct Professor School of Medicine Indiana University None None None AHA* HRS* Indiana Clinical Translational Sciences Institute/ Strategic Research Initiative* ACC AHA AZCert QT drugs list, credible meds.


org None Plaintiff, Drug-induced torsades de pointes, John L. Sapp Official Reviewer HRS Interim Head Division of Cardiology QEII Health Sciences Centre Professor of Medicine Dalhousie University Biosense Webster* Medtronic St. Jude None None Biosense Webster* Canadian Institute of Health Research* DSMB Phillips healthcare* St. Jude Medical* ARTESiA Medtronic Optisure Registry St. Jude None None (Continued) CLINICAL STATEMENTS AND GUIDELINES Joseph Edward Marine Official Reviewer ACC Associate Professor of Medicine Johns Hopkins University School of Medicine None None None None UpToDate None None Kathleen T. Hickey Official Reviewer AHA Professor of Nursing Columbia University Medical Center None None None None None None None Kenneth A. Ellenbogen Content Reviewer Chief of Cardiology Virginia Commonwealth University Medical Center AHA AtriCure* Biosense Webster* Biotronik* Boston Science* Capricor HRS Janssen Medtronic* Pfizer* Sentra heart St. Jude Medical* None None AtriCure* Biosense Webster* Boston Science* Daiichi Sankyo Medtronic* Medtronic (DSMB)* NIH* Pfizer* Biosense Webster* Boston Science* Circulation Heart Rhythm JACC Medtronic* PACE Sanofi Aventis None None Kim K. Birtcher Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines University of Houston College of Pharmacology Jones and Bartlett Learning None None None Accreditation Council for Clinical Lipidology University of Houston College of Pharmacology* Walgreens* None Kristen B. Campbell Content Reviewer Duke University Hospital None None None None None None None Kristen K. Patton Content Reviewer Professor of Medicine University of Washington None None None None ABIM ACGME AHA FDA HRS None None L. Brent Mitchell Content Reviewer Professor Department of Cardiac Sciences Libin Cardiovascular Institute of Alberta University of Calgary Alberta Health Services Boehringer Ingelheim* Forest Pharmaceuticals Guidnat Canada* Medtronic Canada* Medtronic Inc* Merck Pfizer* Servier Canada* None None Boston Scientific* ARTESIA Health Protection Branch, Government of Canada None None Martin Borggrefe Content Reviewer I Medizinische KlinikKlinikum Mannheim GmbHUniversit tsklinikum Bayer Health Care Boehringer Ingelheim Impulse Dynamics Sanofi Aventis St. Jude Medical None None German Centre for Cardiovascular Research* None None None Mathew D. Hutchinson Official Reviewer HRS Professor of Medicine University of Arizona College of Medicine Tucson St. Jude Medical None None None None None None Matthew W. Martinez Content Reviewer Sports and Exercise EP Council Lehigh Valley Health Network None None None None None None None Melissa R. Robinson Content Reviewer Director Complex Ablation Program University of Washington Medtronic* Abbott* Boston Scientific* None None None None None None Michael J. Silka Content Reviewer Children s Hospital Los Angeles None None None None None None Defendant, ICD implantation, Miguel A. Quinones Content Reviewer Methodist DeBakey Heart and Vascular Center None None None None Houston Methodist Hospital* None None Mitchell T. Saltzberg Organizational Reviewer HFSA Jefferson Medical College Christiana Care Health System None None Nephroceuticals* Stem Cell Theranostics* None None None None Appendix 2.


Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Salary Expert Witness (Continued) CLINICAL STATEMENTS AND GUIDELINES N.A.


Mark Estes III Content Reviewer Professor of Medicine Tufts University School of Medicine Boston Scientific* Medtronic* St. Jude Medical* None None Boston Scientific* International Board of Heart Rhythm Examiners Medtronic* St. Jude Medical* None None None Norma M. Keller Official Reviewer ACC New York University Medical Center None None None None None None None Peter Leong-Sit Content Reviewer HRS Associate Professor of Medicine Western University London Health Sciences Centre Medtronic Canada Bayer Healthcare Pharmaceuticals Biosense Webster Johnson and Johnson None None None Bayer Healthcare Pharmaceuticals* None Rachel J. Lampert Content Reviewer Yale University School of Medicine Section of Cardiology Medtronic* None None Boston Scientific* GE Medical* Medtronic, Inc.* St. Jude Medical* None None None Sami Viskin Content Reviewer Tel Aviv Medical Center Department of Cardiology Boston Scientific European Strategy Advisory Board None None None None None None Samuel S. Gidding Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines Dupont Hospital for Children Nemours Cardiac Center Familial Hypercholesterolemia Foundation Regenxbio None None Familial Hypercholestrolemia Foundation NIH Grants* Cardiology Division Head None None Silvia G. Priori Content Reviewer Professore Ordinario di Cardiologia Universit di Pavia Direttore Scientifico Istituti Clinici Scientifici Maugeri Pavia, Italia Ambry Genetics Boston Scientific Medtronic Medtronic, Inc. None Audentes Therapeutics Inc* Gilead Sciences* HRS None None Susan Strong Official Reviewer AHA Sabin Middle School None None None None None None None Win-Kuang Shen Content Reviewer Professor of Medicine Consultant Mayo Clinic Arizona, Phoenix Campus None None None None None None None Zachary D. Goldberger Official Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines Lead Reviewer Assistant Professor of Medicine Division of Cardiology Harborview Medical Center University of Washington School of Medicine RubiconMD None None None None None None This table represents the relationships of reviewers with industry and other entities that were disclosed at the time of peer review, including those not deemed to be relevant to this document, at the time this document was under review.


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 $5000 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. Names are listed in alphabetical order within each category of review. Please refer to http://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees. *Significant relationship. No financial benefit. This disclosure was entered under the Clinical Trial Enroller category in the ACC s disclosure system. To appear in this category, the author acknowledges that there is no direct or institutional relationship with the trial sponsor as defined in the ACC/AHA Disclosure Policy for Writing Committees.


To appear in this category, the author acknowledges that there is no direct or institutional relationship with the trial sponsor as defined in the ACC/AHA Disclosure Policy for Writing Committees. ABIM indicates American Board of Internal Medicine; ACC, American College of Cardiology; ACGME, Accreditation Council for Graduate Medical Education; AHA, American Heart Association; ARTESiA, Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; BEAT-HF, Better Effectiveness After Transition Heart Failure DSMB, data safety monitoring board; ENDEAVOUR, carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma; EP, electrophysiology; FDA, US Food and Drug Administration; HFSA, Heart Failure Society of America; HRS, Heart Rhythm Society; ICD, implantable cardioverter-defibrillator; JACC, Journal of the American College of Cardiology; NIH, National Institutes of Health; NHLBI, National Heart, Lung, and Blood Institute; and PACE, Programs of All- Inclusive Care for the Elderly. Appendix 2. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Salary Expert Witness


2015 ACC/AHA/SCAI Focused Update 2015 by the American College of Cardiology Foundation, the American Heart Association, Inc., and the Society for Cardiovascular Angiography and Interventions. Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0000000000000336 *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendixes 1 and 2 for detailed information. ACC/AHA Representative. SCAI Representative. ACC/AHA Task Force on Clinical Practice Guidelines Liaison. Dr. Deborah D. Ascheim accepted a position at Capricor Therapeutics in August 2015, after the writing effort was completed. In accordance with ACC/AHA policy, she recused herself from the final voting process. ACP Representative. #ACEP Representative. **Former Task Force member; current member during the writing effort. This document was approved by the American College of Cardiology Board of Trustees and Executive Committee, the American Heart Association Science Advisory and Coordinating Committee, and the Society of Cardiovascular Angiography and Interventions in September 2015, and by the American Heart Association Executive Committee in October 2015. The online-only Comprehensive RWI Data Supplement table is available with this article at http://circ.ahajournals.org/lookup/suppl/ doi:10.1161/CIR.0000000000000336/-/DC1. The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/CIR.0000000000000336/-/DC2. TheAmerican HeartAssociation requests that this document be cited as follows: Levine GN, O Gara PT, Bates ER, Blankenship JC, Kushner FG,Ascheim DD, Bailey SR, Bittl JA, Brindis RG, Casey DE Jr, Cercek B, Chambers CE, Chung MK, de Lemos JA, Diercks DB, Ellis SG, Fang JC, Franklin BA, Granger CB, Guyton RA, Hollenberg SM, Khot UN, Krumholz HM, Lange RA, Linderbaum JA, Mauri L, Mehran R, Morrow DA, Moussa ID, Mukherjee D, Newby LK, Ornato JP, Ou N, Radford MJ,Tamis-Holland JE,Ting HH,Tommaso CL,Tracy CM,WooYJ, Zhao DX.


TheAmerican HeartAssociation requests that this document be cited as follows: Levine GN, O Gara PT, Bates ER, Blankenship JC, Kushner FG,Ascheim DD, Bailey SR, Bittl JA, Brindis RG, Casey DE Jr, Cercek B, Chambers CE, Chung MK, de Lemos JA, Diercks DB, Ellis SG, Fang JC, Franklin BA, Granger CB, Guyton RA, Hollenberg SM, Khot UN, Krumholz HM, Lange RA, Linderbaum JA, Mauri L, Mehran R, Morrow DA, Moussa ID, Mukherjee D, Newby LK, Ornato JP, Ou N, Radford MJ,Tamis-Holland JE,Ting HH,Tommaso CL,Tracy CM,WooYJ, Zhao DX. 2015ACC/AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011ACCF/AHA/SCAI guideline for percutaneous coronary intervention and the 2013ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of theAmerican College of Cardiology/American HeartAssociation Task Force on Clinical Practice Guidelines and the Society for CardiovascularAngiography and Interventions. Circulation. 2016;133:1135 1147. This article has been copublished in the Journal of the American College of Cardiology and Catheterization and Cardiovascular Interventions. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org), the American Heart Association (my.americanheart.org), and the Society for Cardiovascular Angiography and Interventions (www.scai.org). A copy of the document is available at http:// professional.heart.org/statements by using either Search for Guidelines & Statements or the Browse By Topic area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. Expert peer review of AHA Scientific Statements is conducted by the AHA Office of Science Operations. For more on AHA statements and guidelines development, visit http://professional.heart.org/statements. Select the Guidelines & Statements drop-down menu, then click Publication Development. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/Copyright- Permission-Guidelines_UCM_300404_Article.jsp.


Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.heart.org/HEARTORG/General/Copyright- Permission-Guidelines_UCM_300404_Article.jsp. A link to the Copyright Permissions Request Form appears on the right side of the page.


A link to the Copyright Permissions Request Form appears on the right side of the page. 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions Endorsed by the Latin American Society of Interventional Cardiology PCI WRITING COMMITTEE* Glenn N. Levine, MD, FACC, FAHA, Chair ; Eric R. Bates, MD, FACC, FAHA, FSCAI, Vice Chair* ; James C. Blankenship, MD, FACC, FAHA, FSCAI, Vice Chair* ; Steven R. Bailey, MD, FACC, FSCAI* ; John A. Bittl, MD, FACC ; Bojan Cercek, MD, FACC, FAHA ; Charles E. Chambers, MD, FACC, FSCAI ; Stephen G. Ellis, MD, FACC* ; Robert A. Guyton, MD, FACC ; Steven M. Hollenberg, MD, FACC* ; Umesh N. Khot, MD, FACC* ; Richard A. Lange, MD, FACC, FAHA ; Laura Mauri, MD, MSc, FACC, FSCAI* ; Roxana Mehran, MD, FACC, FAHA, FSCAI* ; Issam D. Moussa, MD, FACC, FAHA, FSCAI ; Debabrata Mukherjee, MD, FACC, FAHA, FSCAI ; Henry H. Ting, MD, FACC, FAHA STEMI WRITING COMMITTEE* Patrick T. O Gara, MD, FACC, FAHA, Chair ; Frederick G. Kushner, MD, FACC, FAHA, FSCAI, Vice Chair ; Deborah D. Ascheim, MD, FACC ; Ralph G. Brindis, MD, MPH, MACC, FSCAI, FAHA ; Donald E. Casey, Jr, MD, MPH, MBA, FAHA ; Mina K. Chung, MD, FACC, FAHA* ; James A. de Lemos, MD, FACC* ; Deborah B. Diercks, MD, MSc#; James C. Fang, MD, FACC, FAHA* ; Barry A. Franklin, PhD, FAHA ; Christopher B. Granger, MD, FACC, FAHA* ; Harlan M. Krumholz, MD, SM, FACC, FAHA* ; Jane A. Linderbaum, MS, CNP-BC ; David A. Morrow, MD, MPH, FACC, FAHA* ; L. Kristin Newby, MD, MHS, FACC, FAHA* ; Joseph P. Ornato, MD, FACC, FAHA, FACP, FACEP* ; Narith Ou, PharmD ; Martha J. Radford, MD, FACC, FAHA ; Jacqueline E. Tamis-Holland, MD, FACC, FSCAI ; Carl L. Tommaso, MD, FACC, FAHA, MSCAI ; Cynthia M. Tracy, MD, FACC, FAHA ; Y. Joseph Woo, MD, FACC, FAHA ; David X. Zhao, MD, FACC* Table of Contents Preamble 1136 1.


Introduction 1137 1.1. Methodology and Evidence Review 1137 1.2. Organization of the GWC 1137 1.3. Review and Approval 1137 2. Culprit Artery Only Versus Multivessel PCI 1137 3. Aspiration Thrombectomy 1139 References 1140 Appendix 1. Author Relationships With Industry and Other Entities (Relevant) 1142 Appendix 2. Author Relationships With Industry and Other Entities (Relevant) 1143 Appendix 3. Reviewer Relationships With Industry and Other Entities (Relevant) 2015 Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction (Combined Peer Reviewers From 2011 PCI and 2013 STEMI Guidelines) 1145 Preamble To ensure that guidelines reflect current knowledge, avail- able treatment options, and optimum medical care, existing clinical practice guideline recommendations are modified and new recommendations are added in response to new data, medications or devices. To keep pace with evolving evidence, the American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Clinical Practice Guidelines ( Task Force ) has issued this focused update to revise guide- line recommendations on the basis of recently published data. This update is not based on a complete literature review from the date of previous guideline publications, but it has been subject to rigorous, multilevel review and approval, similar to the full guidelines. For specific focused update criteria and additional methodological details, please see the ACC/AHA guideline methodology manual.1 Modernization In response to published reports from the Institute of Medicine2,3 and ACC/AHA mandates,4 7 processes have changed leading to adoption of a knowledge byte format. This entails delineation of recommendations addressing specific clinical questions, fol- lowed by concise text, with hyperlinks to supportive evidence.


This entails delineation of recommendations addressing specific clinical questions, fol- lowed by concise text, with hyperlinks to supportive evidence. This approach better accommodates time constraints on busy clinicians, facilitates easier access to recommendations via electronic search engines and other evolving technology (eg, smart phone apps), and supports the evolution of guidelines as living documents that can be dynamically updated as needed. Intended Use Practice guidelines provide recommendations applicable to patients with or at risk of developing cardiovascular dis- ease. The focus is on medical practice in the United States, but guidelines developed in collaboration with other organi- zations may have a broader target. Although guidelines may inform regulatory or payer decisions, they are intended to improve quality of care in the interest of patients. Class of Recommendation and Level of Evidence The Class of Recommendation (COR) and Level of Evidence (LOE) are derived independently of one another according to established criteria. The COR indicates the strength of recommendation, encompassing the estimated magnitude and certainty of benefit of a clinical action in proportion to risk. The LOE rates the quality of scientific evidence sup- porting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources Relationships With Industry and Other Entities The ACC and AHA sponsor the guidelines without commer- cial support, and members volunteer their time. The Task Force zealously avoids actual, potential, or perceived conflicts of interest that might arise through relationships with indus- try or other entities (RWI). All Guideline Writing Committee (GWC) members and reviewers are required to disclose current industry relationships or personal interests from 12 months before initiation of the writing effort.


All Guideline Writing Committee (GWC) members and reviewers are required to disclose current industry relationships or personal interests from 12 months before initiation of the writing effort. Management of RWI involves selecting a balanced GWC and assuring that the chair and a majority of committee members have no rele- vant RWI (Appendixes 1 and 2). Members are restricted with regard to writing or voting on sections to which their RWI apply. For transparency, members comprehensive disclosure information is available online. Comprehensive disclosure information for the Task Force is also available online. The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds representing different geographic ACC/AHA TASK FORCE MEMBERS Jonathan L. Halperin, MD, FACC, FAHA, Chair; Glenn N. Levine, MD, FACC, FAHA, Chair-Elect; Jeffrey L. Anderson, MD, FACC, FAHA, Immediate Past Chair**; Nancy M. Albert, PhD, RN, FAHA**; Sana M. Al-Khatib, MD, MHS, FACC, FAHA; Kim K. Birtcher, PharmD, MS, AACC; Biykem Bozkurt, MD, PhD, FACC, FAHA; Ralph G. Brindis, MD, MPH, MACC; Joaquin E. Cigarroa, MD, FACC; Lesley H. Curtis, PhD, FAHA; Lee A. Fleisher, MD, FACC, FAHA; Federico Gentile, MD, FACC; Samuel Gidding, MD, FAHA; Mark A. Hlatky, MD, FACC; John Ikonomidis, MD, PhD, FAHA; Jose Joglar, MD, FACC, FAHA; Richard J. Kovacs, MD, FACC, FAHA**; E. Magnus Ohman, MD, FACC**; Susan J. Pressler, PhD, RN, FAHA; Frank W. Sellke, MD, FACC, FAHA**; Win-Kuang Shen, MD, FACC, FAHA**; Duminda N. Wijeysundera, MD, PhD Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1137 regions, sexes, ethnicities, intellectual perspectives/biases, and scopes of clinical practice, and by inviting organizations and professional societies with related interests and expertise to participate as partners or collaborators.


The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds representing different geographic ACC/AHA TASK FORCE MEMBERS Jonathan L. Halperin, MD, FACC, FAHA, Chair; Glenn N. Levine, MD, FACC, FAHA, Chair-Elect; Jeffrey L. Anderson, MD, FACC, FAHA, Immediate Past Chair**; Nancy M. Albert, PhD, RN, FAHA**; Sana M. Al-Khatib, MD, MHS, FACC, FAHA; Kim K. Birtcher, PharmD, MS, AACC; Biykem Bozkurt, MD, PhD, FACC, FAHA; Ralph G. Brindis, MD, MPH, MACC; Joaquin E. Cigarroa, MD, FACC; Lesley H. Curtis, PhD, FAHA; Lee A. Fleisher, MD, FACC, FAHA; Federico Gentile, MD, FACC; Samuel Gidding, MD, FAHA; Mark A. Hlatky, MD, FACC; John Ikonomidis, MD, PhD, FAHA; Jose Joglar, MD, FACC, FAHA; Richard J. Kovacs, MD, FACC, FAHA**; E. Magnus Ohman, MD, FACC**; Susan J. Pressler, PhD, RN, FAHA; Frank W. Sellke, MD, FACC, FAHA**; Win-Kuang Shen, MD, FACC, FAHA**; Duminda N. Wijeysundera, MD, PhD Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1137 regions, sexes, ethnicities, intellectual perspectives/biases, and scopes of clinical practice, and by inviting organizations and professional societies with related interests and expertise to participate as partners or collaborators. Related Issues For additional information pertaining to the methodol- ogy for grading evidence, assessment of benefit and harm, shared decision making between the patient and clinician, structure of evidence tables and summaries, standardized terminology for articulating recommendations, organi- zational involvement, peer review, and policies for peri- odic assessment and updating of guideline documents, we encourage readers to consult the ACC/AHA guideline The recommendations in this focused update represent the official policy of the ACC and AHA until superseded by pub- lished addenda, statements of clarification, focused updates, or revised full-text guidelines. To ensure that guidelines remain current, new data are reviewed biannually to determine whether recommendations should be modified.


To ensure that guidelines remain current, new data are reviewed biannually to determine whether recommendations should be modified. In general, full revisions are posted in 5-year cycles.1 Jonathan L. Halperin, MD, FACC, FAHA Chair, ACC/AHA Task Force on Clinical Practice Guidelines The scope of this focused update is limited to considerations relevant to multivessel percutaneous coronary intervention (PCI) and thrombus aspiration in patients with ST-elevation myocardial infarction (STEMI) undergoing primary PCI. 1.1. Methodology and Evidence Review Clinical trials presented at the major cardiology organizations 2013 to 2015 annual scientific meetings and other selected reports published in a peer-reviewed format through August 2015 were reviewed by the 2011 PCI and 2013 STEMI GWCs and the Task Force to identify trials and other key data that might affect guideline recommendations. The information considered important enough to prompt updated recommen- dations is included in evidence tables in the Online Data Supplement. Consult the full-text versions of the 2011 PCI and for recommendations in clini- cal areas not addressed in the focused update. The indi- vidual recommendations in this focused update will be incorporated into future revisions or updates of the full-text guidelines. 1.2. Organization of the GWC For this focused update, representative members of the 2011 PCI and 2013 STEMI GWCs were invited to participate. Members were required to disclose all RWI relevant to the topics under consideration. The entire membership of both GWCs voted on the revised recommendations and text. The latter group was composed of experts representing cardiovascular medicine, interventional cardiology, electrophysiology, heart failure, cardiac surgery, emergency medicine, internal medicine, car- diac rehabilitation nursing, and pharmacy. The GWC included representatives from the ACC, AHA, American College of Physicians, American College of Emergency Physicians, and Society for Cardiovascular Angiography and Interventions (SCAI).


The GWC included representatives from the ACC, AHA, American College of Physicians, American College of Emergency Physicians, and Society for Cardiovascular Angiography and Interventions (SCAI). 1.3. Review and Approval This document was reviewed predominantly by the prior reviewers from the respective 2011 and 2013 guidelines. These included 8 official reviewers jointly nominated by the ACC and AHA, 4 official/organizational reviewers nominated by SCAI, and 25 individual content reviewers. Reviewers RWI information was distributed to the GWC and is published in this document (Appendix 3). This document was approved for publication by the govern- ing bodies of theACC, theAHA, and the SCAI and was endorsed by the Latin American Society of Interventional Cardiology. 2. Culprit Artery Only Versus Multivessel PCI (See Section 5.2.2.2 of 2011 PCI guideline and Section 4.1.1 of 2013 STEMI guideline for additional recommendations.) Approximately 50% of patients with STEMI have multi- PCI options for patients with STEMI and multivessel disease include: 1) culprit artery only primary PCI, with PCI of nonculprit arteries only for spontaneous isch- emia or intermediate- or high-risk findings on predischarge noninvasive testing; 2) multivessel PCI at the time of primary PCI; or 3) culprit artery only primary PCI followed by staged PCI of nonculprit arteries. Observational studies, randomized controlled trials (RCTs), and meta-analyses comparing culprit artery only PCI with multivessel PCI have reported conflict- likely because of differing inclusion criteria, study protocols, timing of multivessel PCI, statistical heterogeneity, and variable endpoints (Data Supplement).


Observational studies, randomized controlled trials (RCTs), and meta-analyses comparing culprit artery only PCI with multivessel PCI have reported conflict- likely because of differing inclusion criteria, study protocols, timing of multivessel PCI, statistical heterogeneity, and variable endpoints (Data Supplement). Previous clinical practice guidelines recommended against PCI of nonculprit artery stenoses at the time of primary PCI in hemodynamically stable patients with STEMI.9,10 Planning for routine, staged PCI of noninfarct artery stenoses on the basis of the initial angiographic findings was not addressed in these previous guidelines, and noninfarct artery PCI was considered only in the limited context of spontaneous isch- emia or high-risk findings on predischarge noninvasive test- ing. The earlier recommendations were based in part on safety concerns, which included increased risks for procedural com- plications, longer procedural time, contrast nephropathy, and stent thrombosis in a prothrombotic and proinflammatory and in part on the findings from many observational studies and meta-analyses of trends toward or statistically sig- nificant worse outcomes in those who underwent multivessel Four RCTs have since suggested that a strategy of multi- vessel PCI, either at the time of primary PCI or as a planned, staged procedure, may be beneficial and safe in selected patients with STEMI17,18,24,27 (Data Supplement). In the PRAMI (Preventive Angioplasty in Acute Myocardial Infarction) trial the composite primary outcome of cardiac death, nonfatal myocardial infarction (MI), or refractory angina occurred in 21 patients (9%) treated with multivessel primary PCI, compared with 53 patients (22%) treated with culprit artery only PCI (HR: 0.35; 95% CI: 0.21 to 0.58; P<0.001). In the CvLPRIT (Complete Versus Culprit-Lesion Only Primary PCI) trial,18 296 patients were randomized to culprit artery only or multivessel PCI during the index hospitaliza- tion (72% underwent multivessel primary PCI).


In the CvLPRIT (Complete Versus Culprit-Lesion Only Primary PCI) trial,18 296 patients were randomized to culprit artery only or multivessel PCI during the index hospitaliza- tion (72% underwent multivessel primary PCI). The compos- ite primary outcome of death, reinfarction, heart failure, and ischemia-driven revascularization at 12 months occurred in 15 patients (10%) who underwent multivessel PCI, compared with 31 patients (21%) receiving culprit artery only PCI (HR: PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) the composite primary outcome of all-cause death, nonfatal MI, or ischemia-driven revascularization of non- culprit artery disease occurred in 40 of 314 patients (13%) who underwent multivessel staged PCI guided by angiogra- phy and fractional flow reserve before discharge, versus 68 of 313 patients (22%) treated with culprit artery only PCI (HR: (Primary Angioplasty in Patients Transferred From General Community Hospitals to Specialized PTCA Units With or Without Emergency Thrombolysis) trial,27 214 patients with Table 1. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated August 2015) Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1139 STEMI were randomized to staged (3 to 40 days after the index procedure) revascularization of all 70% diameter stenosis noninfarct lesions or culprit-only PCI. Preliminary results at 38 months mean follow-up showed no between-group differ- ences in the composite primary endpoint of all-cause death, nonfatal MI, and stroke. On the basis of these findings,17,18,24,27 the prior Class III (Harm) recommendation with regard to multivessel primary PCI in hemodynamically stable patients with STEMI has been upgraded and modified to a Class IIb recommendation to include consideration of multivessel PCI, either at the time of primary PCI or as a planned, staged procedure.


On the basis of these findings,17,18,24,27 the prior Class III (Harm) recommendation with regard to multivessel primary PCI in hemodynamically stable patients with STEMI has been upgraded and modified to a Class IIb recommendation to include consideration of multivessel PCI, either at the time of primary PCI or as a planned, staged procedure. The writ- ing committee emphasizes that this change should not be interpreted as endorsing the routine performance of multives- sel PCI in all patients with STEMI and multivessel disease. Rather, when considering the indications for and timing of multivessel PCI, physicians should integrate clinical data, lesion severity/complexity, and risk of contrast nephropathy to determine the optimal strategy. The preceding discussion and recommendations apply to the strategy of routine PCI of noninfarct related arteries in hemodynamically stable patients. Recommendations in the 2013 STEMI guideline with regard to PCI of a non infarct- related artery at a time separate from primary PCI in patients who have spontaneous symptoms and myocardial ischemia or who have intermediate- or high-risk findings on noninva- sive testing (Section 6.3 of that guideline) remain operative. Although several observational studies19,20 and a network have suggested that multivessel staged PCI may be associated with better outcome than multivessel primary PCI, there are insufficient observational data and no randomized data at this time to inform a recommenda- tion with regard to the optimal timing of nonculprit vessel PCI. Additional trial data that will help further clarify this issue are awaited. Issues related to the optimal method of evaluating nonculprit lesions (eg, percent diameter stenosis, fractional flow reserve) are beyond the scope of this focused update. 3. Aspiration Thrombectomy (See Section 5.5.2 of the 2011 PCI guideline and Section 4.2 of the 2013 STEMI guideline for additional recommendations.)


Aspiration Thrombectomy (See Section 5.5.2 of the 2011 PCI guideline and Section 4.2 of the 2013 STEMI guideline for additional recommendations.) Class IIa recommendation for aspiration thrombectomy before primary PCI was based on the results of 2 RCTs29,31,32 and 1 meta-anal- and was driven in large measure by the results of TAPAS (Thrombus Aspiration During Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction Study), a single- center study that randomized 1071 patients with STEMI to aspiration thrombectomy before primary PCI or primary PCI Three multicenter trials, 2 of which enrolled signifi- cantly more patients than prior aspiration thrombectomy tri- als, have prompted reevaluation of this recommendation. In the INFUSE-AMI (Intracoronary Abciximab and Aspiration Thrombectomy in Patients With Large Anterior Myocardial of 452 patients with anterior STEMI due to proximal or mid-left anterior descending occlusion, infarct size was not reduced by aspiration thrombectomy before primary PCI. The TASTE (Thrombus Aspiration During ST-Segment Elevation Myocardial Infarction) trial (n=7244) incorporated a unique design that allowed randomization within an exist- ing national registry, resulting in enrollment of a remarkably high proportion of eligible patients.34,36 No significant 30-day or 1-year differences were found between the group that received aspiration thrombectomy before primary PCI and the group that received primary PCI only with regard to death, reinfarc- tion, stent thrombosis, target lesion revascularization, or a com- posite of major adverse cardiac events. The TOTAL (Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI) trial randomized 10,732 patients with STEMI to aspiration thrombectomy before primary PCI or pri- mary PCI only.35 Bailout thrombectomy was performed in 7.1% of the primary PCI only group, whereas the rate of crossover from aspiration thrombectomy before primary PCI to primary PCI only was 4.6%.


The TOTAL (Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI) trial randomized 10,732 patients with STEMI to aspiration thrombectomy before primary PCI or pri- mary PCI only.35 Bailout thrombectomy was performed in 7.1% of the primary PCI only group, whereas the rate of crossover from aspiration thrombectomy before primary PCI to primary PCI only was 4.6%. There were no differences between the 2 treatment groups, either in the primary composite endpoint of cardiovascular death, recurrent MI, cardiogenic shock, or New York Heart Association class IV heart failure at 180 days, or in the individual components of the primary endpoint, stent thrombosis, or target-vessel revascularization. There was a small but statistically significant increase in the rate of stroke in Recommendation 2015 Focused Update Recommendation Comment Class III: Harm Class IIb PCI should not be performed in a noninfarct artery at the time of primary PCI in patients with STEMI who are hemodynamically (Level of Evidence: B) PCI of a noninfarct artery may be considered in selected patients with STEMI and multivessel disease who are hemodynamically stable, either at the time of primary PCI or as a planned staged (Level of Evidence: B-R) Modified recommendation (changed class from III: Harm to IIb and expanded time frame in which multivessel PCI could be performed). PCI indicates percutaneous coronary intervention; and STEMI, ST-elevation myocardial infarction. Recommendation 2015 Focused Update Recommendations Comments Class IIa Class IIb Manual aspiration thrombectomy is reasonable for patients undergoing (Level of Evidence: B) The usefulness of selective and bailout aspiration thrombectomy in patients undergoing primary PCI is not well established.33 37 (Level of Evidence: C-LD) Modified recommendation (Class changed from IIa to IIb for selective and bailout aspiration thrombectomy before PCI).


Recommendation 2015 Focused Update Recommendations Comments Class IIa Class IIb Manual aspiration thrombectomy is reasonable for patients undergoing (Level of Evidence: B) The usefulness of selective and bailout aspiration thrombectomy in patients undergoing primary PCI is not well established.33 37 (Level of Evidence: C-LD) Modified recommendation (Class changed from IIa to IIb for selective and bailout aspiration thrombectomy before PCI). Class III: No Benefit Routine aspiration thrombectomy before primary PCI is not (Level of Evidence: A) New recommenda- tion ( Class III: No Benefit added for routine aspiration thrombectomy before PCI). PCI indicates percutaneous coronary intervention; and LD, limited data. the aspiration thrombectomy group. An updated meta-analysis that included these 3 trials among a total of 17 trials (n=20960) found no significant reduction in death, reinfarction, or stent thrombosis with routine aspiration thrombectomy. Aspiration thrombectomy was associated with a small but nonsignificant increase in the risk of stroke.33 Several previous studies have found that higher thrombus burden in patients with STEMI is independently associated with higher risks of distal embolization, no-reflow phenom- enon, transmural myocardial necrosis, major adverse cardiac events, stent thrombosis, and death.38 42 However, subgroup analyses from the TASTE and TOTAL trials did not suggest rel- ative benefit from aspiration thrombectomy before primary PCI in patients with higher thrombus burden or in patients with ini- tial Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 1 or left anterior descending artery/anterior infarction.34,35 On the basis of the results of these studies, the prior Class IIa recommendation for aspiration thrombectomy has been changed. Routine aspiration thrombectomy before primary PCI is now not recommended (Class III: No Benefit, LOE A). There are insufficient data to assess the potential benefit of a strategy of selective or bailout aspiration thrombectomy (Class IIb, LOE C-LD).


There are insufficient data to assess the potential benefit of a strategy of selective or bailout aspiration thrombectomy (Class IIb, LOE C-LD). Bailout aspiration thrombectomy is defined as thrombectomy that was initially unplanned but was later used during the procedure because of unsatisfactory initial result or procedural complication, analogous to the defi- nition of bailout glycoprotein IIb/IIIa use. It should be noted that the preceding recommendations and text apply only to aspiration thrombectomy; no clini- cal benefit for routine rheolytic thrombectomy has been demonstrated in patients with STEMI undergoing primary Presidents and Staff American College of Cardiology Kim A. Williams, Sr, MD, FACC, FAHA, President Shalom Jacobovitz, Chief Executive Officer William J. Oetgen, MD, MBA, FACC, Executive Vice President, Science, Education, Quality, and Publications Amelia Scholtz, PhD, Publications Manager, Science, Education, and Quality American College of Cardiology/American Heart Association Lisa Bradfield, CAE, Director, Science and Clinical Policy Abdul R. Abdullah, MD, Associate Science and Medicine Advisor Allison Rabinowitz, Project Manager, Science and Clinical Policy American Heart Association Mark A. Creager, MD, FAHA, FACC, President Nancy Brown, Chief Executive Officer Rose Marie Robertson, MD, FAHA, Chief Science Officer Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Office of Science Operations Jody Hundley, Production Manager, Scientific Publications, Office of Science Operations References 1. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. American College of Cardiology and American Heart Association. 2010. Available at: http://assets.cardiosource.com/Methodology_Manual_ for_ACC_AHA_Writing_Committees.pdf and http://my.americanheart. org/idc/groups/ahamah-public/@wcm/@sop/documents/downloadable/ ucm_319826.pdf. Accessed January 23, 2015. 2. Committee on Standards for Developing Trustworthy Clinical Practice Guidelines, Institute of Medicine (US). Clinical Practice Guidelines We Can Trust. Washington, DC: National Academies Press; 2011. 3. Committee on Standards for Systematic Reviews of Comparative Effectiveness Research, Institute of Medicine (US).


Committee on Standards for Systematic Reviews of Comparative Effectiveness Research, Institute of Medicine (US). Finding What Works in Health Care: Standards for Systematic Reviews. Washington, DC: National Academies Press; 2011. 4. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA statement on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines. Circulation. 2014;129:2329 45. 5. Arnett DK, Goodman RA, Halperin JL, et al. AHA/ACC/HHS strategies to enhance application of clinical practice guidelines in patients with car- diovascular disease and comorbid conditions: from the American Heart Association, American College of Cardiology, and U.S. Department of Health and Human Services. Circulation. 2014;130:1662 7. 6. Jacobs AK, Kushner FG, Ettinger SM, et al. ACCF/AHA clinical practice guideline methodology summit report: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:268 310. 7. Jacobs AK, Anderson JL, Halperin JL. The evolution and future of ACC/ AHA clinical practice guidelines: a 30-year journey: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130:1208 17. 8. Halperin JL, Levine GN,Al-Khatib SM, et al. Further evolution of theACC/ AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published online ahead of print September 23, 2015]. Circulation. doi:10.1161/CIR.0000000000000312. Accessed December 7, 2015. 9. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/ SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124:e574 651. 10. O Gara PT, Kushner FG, Ascheim DD, et al.


10. O Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:529 55. 11. Hannan EL, Samadashvili Z, Walford G, et al. Culprit vessel percutaneous coronary intervention versus multivessel and staged percutaneous coro- nary intervention for ST-segment elevation myocardial infarction patients with multivessel disease. JACC Cardiovasc Interv. 2010;3:22 31. 12. Toma M, Buller CE,Westerhout CM, et al. Non-culprit coronary artery percu- taneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial. Eur Heart J. 2010;31:1701 7. 13. Vlaar PJ, Mahmoud KD, Holmes DR Jr, et al. Culprit vessel only versus mul- tivessel and staged percutaneous coronary intervention for multivessel disease in patients presenting with ST-segment elevation myocardial infarction: a pairwise and network meta-analysis. J Am Coll Cardiol. 2011;58:692 703. 14. Cavender MA, Milford-Beland S, Roe MT, et al. Prevalence, predictors, and in- hospital outcomes of non-infarct artery intervention during primary percutane- ous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry).Am J Cardiol. 2009;104:507 13. 15. Corpus RA, House JA, Marso SP, et al. Multivessel percutaneous coronary intervention in patients with multivessel disease and acute myocardial infarction. Am Heart J. 2004;148:493 500. 16. Dziewierz A, Siudak Z, Rakowski T, et al. Impact of multivessel coronary artery disease and noninfarct-related artery revascularization on outcome of patients with ST-elevation myocardial infarction transferred for pri- mary percutaneous coronary intervention (from the EUROTRANSFER Registry). Am J Cardiol. 2010;106:342 7. 17. Engstr mT, Kelb k H, Helqvist S, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI 3-PRIMULTI): an open-label, randomised controlled trial. Lancet. 2015;386:665 71.


Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI 3-PRIMULTI): an open-label, randomised controlled trial. Lancet. 2015;386:665 71. Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1141 18. Gershlick AH, Khan JN, Kelly DJ, et al. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary per- cutaneous coronary intervention for STEMI and multivessel Disease: the CvLPRIT trial. J Am Coll Cardiol. 2015;65:963 72. 19. Kornowski R, Mehran R, Dangas G, et al. Prognostic impact of staged ver- sus one-time multivessel percutaneous intervention in acute myocardial infarction: analysis from the HORIZONS-AMI (harmonizing outcomes with revascularization and stents in acute myocardial infarction) trial. J Am Coll Cardiol. 2011;58:704 11. 20. Manari A, Varani E, Guastaroba P, et al. Long-term outcome in patients with ST segment elevation myocardial infarction and multivessel disease treated with culprit-only, immediate, or staged multivessel percutaneous revascularization strategies: insights from the REAL registry. Catheter Cardiovasc Interv. 2014;84:912 22. 21. Politi L, Sgura F, Rossi R, et al. A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up. Heart. 2010;96:662 7. 22. Roe MT, Cura FA, Joski PS, et al. Initial experience with multivessel per- cutaneous coronary intervention during mechanical reperfusion for acute myocardial infarction. Am J Cardiol. 2001;88:170 3, A6. 23. Varani E, Balducelli M, Aquilina M, et al. Single or multivessel percutane- ous coronary intervention in ST-elevation myocardial infarction patients. Catheter Cardiovasc Interv. 2008;72:927 33. 24. Wald DS, Morris JK, Wald NJ, et al. Randomized trial of preventive angio- plasty in myocardial infarction. N Engl J Med. 2013;369:1115 23. 25. Sorajja P, Gersh BJ, Cox DA, et al.


2013;369:1115 23. 25. Sorajja P, Gersh BJ, Cox DA, et al. Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Eur Heart J. 2007;28:1709 16. 26. Park D-W, Clare RM, Schulte PJ, et al. Extent, location, and clinical sig- nificance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction. JAMA. 2014;312:2019 27. 27. Hlinomaz O. Multivessel coronary disease diagnosed at the time of pri- mary PCI for STEMI: complete revascularization versus conservative strategy. PRAGUE 13 trial. Available at: http://sbhci.org.br/wp-content/ uploads/2015/05/PRAGUE-13-Trial.pdf. Accessed September 10, 2015. tivessel and staged percutaneous coronary intervention for multivessel dis- ease in patients presenting with ST-segment elevation myocardial infarction: a pairwise and network meta-analysis. JAm Coll Cardiol. 2011;58:692 703. 29. Vlaar PJ, Svilaas T, van der Horst IC, et al. Cardiac death and reinfarc- tion after 1 year in the Thrombus Aspiration during Percutaneous coro- nary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet. 2008;371:1915 20. 30. BavryAA, Kumbhani DJ, Bhatt DL. Role of adjunctive thrombectomy and embolic protection devices in acute myocardial infarction: a comprehen- sive meta-analysis of randomized trials. Eur Heart J. 2008;29:2989 3001. 31. Sardella G, Mancone M, Bucciarelli-Ducci C, et al. Thrombus aspiration during primary percutaneous coronary intervention improves myocardial reperfusion and reduces infarct size: the EXPIRA (thrombectomy with export catheter in infarct-related artery during primary percutaneous coronary inter- vention) prospective, randomized trial. J Am Coll Cardiol. 2009;53:309 15. 32. Svilaas T, Vlaar PJ, van der Horst IC, et al. Thrombus aspiration dur- ing primary percutaneous coronary intervention. N Engl J Med. 2008;358:557 67. 33. Elgendy IY, Huo T, Bhatt DL, et al. Is aspiration thrombectomy beneficial in patients undergoing primary percutaneous coronary intervention? Meta- analysis of randomized trials. Circ Cardiovasc Interv. 2015;8:e002258. 34.


Meta- analysis of randomized trials. Circ Cardiovasc Interv. 2015;8:e002258. 34. Fr bert O, Lagerqvist B, Olivecrona GK, et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med. 2013;369:1587 97. 35. Jolly SS, Cairns JA,Yusuf S, et al. Randomized trial of primary PCI with or without routine manual thrombectomy. N Engl J Med. 2015;372:1389 98. 36. Lagerqvist B, Fr bert O, Olivecrona GK, et al. Outcomes 1 year after thrombus aspiration for myocardial infarction. N Engl J Med. 2014;371:1111 20. 37. Stone GW, Maehara A, Witzenbichler B, et al. Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial. JAMA. 2012;307:1817 26. 38. Napodano M, Dariol G, Al Mamary AH, et al. Thrombus burden and myo- cardial damage during primary percutaneous coronary intervention. Am J Cardiol. 2014;113:1449 56. 39. Sianos G, Papafaklis MI, Daemen J, et al.Angiographic stent thrombosis after routine use of drug-eluting stents in ST-segment elevation myocardial infarc- tion: the importance of thrombus burden. JAm Coll Cardiol. 2007;50:573 83. 40. Yip HK, Chen M-C, Chang H-W, et al. Angiographic morphologic fea- tures of infarct-related arteries and timely reperfusion in acute myocardial infarction: predictors of slow-flow and no-reflow phenomenon. Chest. 2002;122:1322 32. 41. Brener SJ, Dambrink J-H, Maehara A, et al. Benefits of optimising coro- nary flow before stenting in primary percutaneous coronary intervention for ST-elevation myocardial infarction: insights from INFUSE-AMI. EuroIntervention. 2014;9:1195 201. 42. Costa RA, Abizaid A, Lotan C, et al. Impact of thrombus burden on out- comes after standard versus mesh-covered stents in acute myocardial infarction (from the MGuard for acute ST elevation reperfusion trial). Am J Cardiol. 2015;115:161 6. 43. Ali A, Cox D, Dib N, et al.


2015;115:161 6. 43. Ali A, Cox D, Dib N, et al. Rheolytic thrombectomy with percutane- ous coronary intervention for infarct size reduction in acute myocardial infarction: 30-day results from a multicenter randomized study. J Am Coll Cardiol. 2006;48:244 52. 44. Migliorini A, Stabile A, Rodriguez AE, et al. Comparison of AngioJet rhe- olytic thrombectomy before direct infarct artery stenting with direct stent- ing alone in patients with acute myocardial infarction. The JETSTENT trial. J Am Coll Cardiol. 2010;56:1298 306. Key Words: AHA Scientific Statements culprit vessel focused update multivessel myocardial infarction primary PCI thrombectomy Appendix 1.


Key Words: AHA Scientific Statements culprit vessel focused update multivessel myocardial infarction primary PCI thrombectomy Appendix 1. Author Relationships With Industry and Other Entities (Relevant) 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction (Percutaneous Coronary Intervention Writing Committee) (November 2014) Committee Member Employer/Title Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* Glenn N. Levine, Chair Baylor College of Medicine Professor of Medicine; Director, Cardiac Care Unit None None None None None None None Eric R. Bates, Vice Chair University of Michigan Professor of Medicine Merck Sanofi-aventis None None None None None 2 and 3 James C. Blankenship, Vice Chair Geisinger Medical Center Director of Cardiology and Cardiac Catheterization Laboratories None None None Abbott Vascular Abiomed Boston Scientific Volcano None None 2 and 3 Steven R. Bailey University of Texas Medical Center Professor of Medicine and Radiology None None None None None None None John A. Bittl Munroe Heart Interventional Cardiologist None None None None None None None Bojan Cercek Cedars-Sinai Medical Center Director, Coronary Care Unit None None None None None None None Charles E. Chambers Penn State Milton S. Hershey Medical Center Professor of Medicine and Radiology None None None None None None None Stephen G. Ellis Cleveland Clinic Foundation Section Head, Invasive and Interventional Cardiology Abbott Boston Scientific Medtronic None None None None None 2 and 3 Robert A. Guyton Emory Clinic, Inc.


Author Relationships With Industry and Other Entities (Relevant) 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction (Percutaneous Coronary Intervention Writing Committee) (November 2014) Committee Member Employer/Title Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* Glenn N. Levine, Chair Baylor College of Medicine Professor of Medicine; Director, Cardiac Care Unit None None None None None None None Eric R. Bates, Vice Chair University of Michigan Professor of Medicine Merck Sanofi-aventis None None None None None 2 and 3 James C. Blankenship, Vice Chair Geisinger Medical Center Director of Cardiology and Cardiac Catheterization Laboratories None None None Abbott Vascular Abiomed Boston Scientific Volcano None None 2 and 3 Steven R. Bailey University of Texas Medical Center Professor of Medicine and Radiology None None None None None None None John A. Bittl Munroe Heart Interventional Cardiologist None None None None None None None Bojan Cercek Cedars-Sinai Medical Center Director, Coronary Care Unit None None None None None None None Charles E. Chambers Penn State Milton S. Hershey Medical Center Professor of Medicine and Radiology None None None None None None None Stephen G. Ellis Cleveland Clinic Foundation Section Head, Invasive and Interventional Cardiology Abbott Boston Scientific Medtronic None None None None None 2 and 3 Robert A. Guyton Emory Clinic, Inc. Professor and Chief, Division of Cardiothoracic Surgery Medtronic None None None None None 2 and 3 Steven M. Hollenberg Cooper Medical School of Rowan University Professor of Medicine None None None None None None None Umesh N. Khot Cleveland Clinic Vice Chairman, Department of Cardiovascular Medicine AstraZeneca None None None None None None Richard A. Lange Texas Tech University Health Sciences Center El Paso President None None None None None None None Laura Mauri Brigham & Women s Hospital Associate Professor of Medicine, Harvard Medical School Medtronic St. Jude Medical None None None Abbott Boston Scientific Bristol-Myers Squibb Cordis Medtronic Cardiovascular Sanofi-aventis Roxana Mehran Columbia University Medical Center Associate Professor of Medicine; Director, Data Coordinating Analysis Center Abbott Vascular Boston Scientific Janssen (Johnson & Johnson) Merck Sanofi-aventis None None BMS/ Sanofi- aventis Regado STENTYS None None 2 and 3 Issam D. Moussa University of Central Florida College of Medicine Professor of Medicine; First Coast Cardiovascular Institute Chief Medical Officer None None None None None None None (Continued) Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1143 Debabrata Mukherjee Texas Tech University Chief, Cardiovascular Medicine None None None None None None None Henry H. Ting New York Presbyterian Hospital, The University Hospital of Columbia and Cornell Senior Vice President and Chief Quality Officer None None None None None None None This table represents the relationships of committee members with industry and other entities that were determined to be relevant to this document.


Professor and Chief, Division of Cardiothoracic Surgery Medtronic None None None None None 2 and 3 Steven M. Hollenberg Cooper Medical School of Rowan University Professor of Medicine None None None None None None None Umesh N. Khot Cleveland Clinic Vice Chairman, Department of Cardiovascular Medicine AstraZeneca None None None None None None Richard A. Lange Texas Tech University Health Sciences Center El Paso President None None None None None None None Laura Mauri Brigham & Women s Hospital Associate Professor of Medicine, Harvard Medical School Medtronic St. Jude Medical None None None Abbott Boston Scientific Bristol-Myers Squibb Cordis Medtronic Cardiovascular Sanofi-aventis Roxana Mehran Columbia University Medical Center Associate Professor of Medicine; Director, Data Coordinating Analysis Center Abbott Vascular Boston Scientific Janssen (Johnson & Johnson) Merck Sanofi-aventis None None BMS/ Sanofi- aventis Regado STENTYS None None 2 and 3 Issam D. Moussa University of Central Florida College of Medicine Professor of Medicine; First Coast Cardiovascular Institute Chief Medical Officer None None None None None None None (Continued) Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1143 Debabrata Mukherjee Texas Tech University Chief, Cardiovascular Medicine None None None None None None None Henry H. Ting New York Presbyterian Hospital, The University Hospital of Columbia and Cornell Senior Vice President and Chief Quality Officer None None None None None None None 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 $5000 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 ACC/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 group members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply. No financial benefit. Significant relationship. ACC indicates American College of Cardiology; AHA, American Heart Association; and SCAI, Society for Cardiovascular Angiography and Interventions. Appendix 1. Continued Committee Member Employer/Title Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* (Continued) Appendix 2.


Continued Committee Member Employer/Title Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* (Continued) Appendix 2. Author Relationships With Industry and Other Entities (Relevant) 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction (ST-Elevation Myocardial Infarction Writing Committee) (February 2014) Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* Patrick T. O Gara, Chair Harvard Medical School Professor of Medicine None None None None None None None Frederick G. Kushner, Vice Chair Tulane University School of Medicine Clinical Professor of Medicine; Heart Clinic of Louisiana Medical Director None None None None None None None Deborah D. Ascheim Mount Sinai School of Medicine Associate Professor; InCHOIR Clinical Director of Research None None None None None None None Ralph G. Brindis UCSF Philip R. Lee Institute for Health Policy Studies Clinical Professor of Medicine None None None None None None None Donald E. Casey, Jr. Thomas Jefferson College of Population Health Adjunct Faculty; Alvarez & Marsal and Founder None None None None None None None Mina K. Chung Cleveland Clinic Foundation Professor of Medicine Boston Scientific Medtronic St. Jude Medical None None Biosense Webster Boston Scientific Medtronic St. Jude Medical None None 2 and 3 James A. de Lemos UT Southwestern Medical Center Professor of Medicine Abbott Diagnostics Novo Nordisc St. Jude Medical None None Abbott Diagnostics None None 2 and 3 Deborah B. Diercks UT Southwestern Medical Center Audre and Bernard Rapoport Distinguished Chair in Clinical Care and Research; Department of Emergency Medicine Professor and Chair None None None None None None None James C. Fang University of Utah Cardiovascular Division Boston Scientific None None None None None 2 and 3 Barry A. Franklin William Beaumont Hospital Director, Cardiac Rehabilitation and Exercise Laboratories None None None None None None None Christopher B. Granger Duke Clinical Research Institute Director, Cardiac Care Unit; Professor of Medicine None None None Medtronic Foundation Merck None None 2 and 3 Harlan M. Krumholz Yale University School of Medicine Professor of Epidemiology and Public Health None None None Johnson & Johnson Medtronic None None 2 and 3 Jane A. Linderbaum Mayo Clinic Assistant Professor of Medicine None None None None None None None David A. Morrow Harvard Medical School Professor of Medicine Abbott Merck None None Abbott GlaxoSmithKline Johnson & Johnson Merck None None 2 and 3 L. Kristin Newby Duke University Medical Center, Division of Cardiology Professor of Medicine Philips None None Merck None None 2 and 3 Joseph P. Ornato Department of Emergency Medicine Virginia Commonwealth University Professor and Chairman None None None None None None None Narith Ou Mayo Clinic Pharmacotherapy Coordinator, Cardiology None None None None None None None Martha J. Radford NYU Langone Medical Center Chief Quality Officer; NYU School of Medicine Professor of Medicine (Cardiology) None None None None None None None Jacqueline E. Tamis-Holland Mount Sinai Saint Luke s Hospital and The Icahn School of Medicine Program Director, Interventional Cardiology Fellowship Program None None None None None None None Carl L. Tommaso Skokie Hospital Director of Catheterization Laboratory; NorthShore University HealthSystems Partner None None None None None None None Cynthia M. Tracy George Washington University Medical Center Associate Director, Division of Cardiology None None None None None None None Y. Joseph Woo Stanford University Professor and Chair, Cardiothoracic Surgery None None None None None None None David X. Zhao Wake Forest Baptist Health Professor of Medicine, Heart and Vascular Center of Excellence Director None None None St. Jude Medical Medtronic None None 2 and 3 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. 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 $5000 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 ACC/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 group members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply. Dr. Deborah D. Ascheim accepted a position at Capricor Therapeutics in August 2015, after the writing effort was completed. According to policy, she recused herself from the final voting process. Significant relationship. No financial benefit.


According to policy, she recused herself from the final voting process. Significant relationship. No financial benefit. ACC indicates American College of Cardiology; AHA, American Heart Association; NYU, New York University; UCSF, University of California San Francisco; and UT, University of Texas. Appendix 2. Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1145 Appendix 3.


Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Voting Recusals by Section* Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1145 Appendix 3. Reviewer Relationships With Industry and Other Entities (Relevant) 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction (Combined Peer Reviewers From 2011 PCI and 2013 STEMI Guidelines) Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Elliott M. Antman Official Reviewer AHA Harvard Medical School Professor of Medicine, Associate Dean for Clinical and Translational Research None None None None None None Deepak L. Bhatt Official Reviewer AHA Harvard Medical School Professor; Interventional Cardiovascular Programs Executive Director None None None Bristol-Myers Squibb* Ischemix* Medtronic* St. Jude Medical Regado Biosciences None Christopher P. Cannon Official Reviewer AHA Harvard Medical School Professor of Medicine; Brigham and Women s Hospital Senior Investigator, TIMI Study Group, Cardiovascular Division Bristol-Myers Squibb Merck Regeneron/ Sanofi-aventis* None None Merck* None None Joaquin E. Cigarroa Official Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Oregon Health & Science University Clinical Professor of Medicine None None None None None None George Dangas Official Reviewer ACC Board of Trustees Icahn School of Medicine Professor of Cardiology and Vascular Surgery; Mount Sinai Medical Center Director, Cardiovascular Innovation Abbott Biosensors Boston Scientific Johnson & Johnson* Merck Osprey Medical* Regado Biosciences None None None Abbott Medtronic Osprey None Charles J. Davidson Official Reviewer SCAI Northwestern University Feinberg School of Medicine Professor of Medicine, Director of Cardiac Catheterization Lab None None None Baxter International None None Kirk N. Garratt Official Reviewer SCAI Hofstra University Medical School Associate Chair of Quality and Research; Professor of Medicine Abbott Boston Scientific The Medicines Company Daiichi-Sankyo/ Eli Lilly AstraZeneca None LifeCuff Technologies Global Delivery Systems None Boston Scientific None Steven L. Goldberg Official Reviewer SCAI University of Washington Medical Center Cath Lab Director Terumo None None None None None G. B. John Mancini Official Reviewer ACC Board of Governors Vancouver Hospital Research Pavilion Professor of Medicine Merck Sanofi-aventis/ Regeneron None None None None None Jonathan M. Tobis Official Reviewer SCAI University of California Los Angeles Professor of Medicine and Cardiology St. Jude Medical None None None None None Jeffrey L. Anderson Content Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Intermountain Medical Center Associate Chief of Cardiology None None None None None None Thomas M. Bashore Content Reviewer Duke University Professor of Medicine None None None None None None James A. Burke Content Reviewer ACC Interventional Scientific Council Lehigh Valley Heart Specialists Associate Chief, Division of Cardiology None None None None None None Jeffrey J. Cavendish Content Reviewer ACC Prevention of Cardiovascular Disease Committee Kaiser Permanente Cardiology Interventional Cardiologist None None None None Abbott None (Continued) Gregory J. Dehmer Content Reviewer ACC Appropriate Use Criteria Texas A&M College of Medicine Professor of Medicine; Scott & White Healthcare None None None None None None John S. Douglas, Jr.


Content Reviewer Emory University Hospital Professor of Medicine None None None Abbott Medtronic None None John P. Erwin III Content Reviewer ACC/AHA Task Force on Performance Measures Texas A&M College of Medicine Associate Professor; Scott & White Healthcare Vice Chair of the Department of Medicine None None None None None None T. Bruce Ferguson Content Reviewer ACC Surgeons Scientific Council East Carolina Institute Brody School of Medicine Professor of Surgery and Physiology None None None None None None Anthony Gershlick Content Reviewer University Hospitals of Leicester, Department of Cardiology Abbott Boston Scientific Cordis Medtronic Abbott None None None None Jonathan L. Halperin Content Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Mt.


Sinai Medical Professor of Medicine Bayer Healthcare Boston Scientific Johnson & Johnson Medtronic None None None None None Howard C. Herrmann Content Reviewer University of Pennsylvania Perelman School of Medicine Professor of Medicine, Director of Interventional Cardiology Program Seimens Medical St. Jude Medical None None Abbott* Medtronic Siemens Medical* St. Jude Medical None None Morton J. Kern Content Reviewer University of California Irvine Professor of Medicine, Associate Chief of the Division of Cardiology Acist Medical Merit Medical* St. Jude Medical* None None None None Fred M. Kosumoto Content Reviewer Mayo Clinic Director, Pacing and Electrophysiology Service None None None None None None David J. Maron Content Reviewer Stanford University School of Medicine Professor of Medicine and Emergency Medicine None None None None None None Douglass A. Morrison Content Reviewer University of Arizona Professor of Medicine; Southern Arizona VA Health Care System Cardiac Catheterization Laboratories, Director None None None None None None Manesh R. Patel Content Reviewer ACC Appropriate Use Criteria Duke University Medical Center Associate Professor of Medicine Bayer Healthcare* Janssen Pharmaceuticals* None None Johnson & Johnson* None None M. Eugene Sherman Content Reviewer ACC Board of Governors Aurora Denver Cardiology None None None None Bristol-Myers Squibb* Hospira* None Daniel I. Simon Content Reviewer University Hospitals Case Medical Center Professor of Cardiovascular Research Cordis/Johnson & Johnson* Janssen Pharmaceuticals/ Johnson & Johnson Medtronic Vascular Merck Abbott None None None None (Continued) Appendix 3.


Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness Levine et al 2015 ACC/AHA/SCAI Focused Update on Primary PCI 1147 Richard W. Snyder Content Reviewer ACC Board of Governors HeartPlace None None None None None None William A. Tansey III Content Reviewer Summit Medical Group Cardiologist None None None None None None David D. Waters Content Reviewer San Francisco General Hospital Chief, Division of Cardiology None None None None Merck None Patrick L. Whitlow Content Reviewer Cleveland Clinic Foundation Director, Interventional Cardiology None None None Abbott Medtronic* David O. Williams Content Reviewer Harvard Medical School Professor of Medicine; Brigham and Women s Hospital None None None None None None Clyde W. Yancy Content Reviewer ACC/AHA Task Force on Practice Guidelines Northwestern University Feinberg School of Medicine Vice Dean for Diversity and Inclusion, Chief of Medicine- Cardiology, Professor None None None None None None Yerem Yeghiazarians Content Reviewer University of California San Francisco Associate Professor None None None None None 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 $5000 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.


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 in this table are modest unless otherwise noted. Names are listed in alphabetical order within each category of review. According to the ACC/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. No financial benefit. ACC indicates American College of Cardiology; AHA, American Heart Association; HF, heart failure; SCAI, Society for Cardiovascular Angiography and Interventions; STEMI, ST-elevation myocardial infarction; PCI, percutaneous coronary interventions; TIMI, Thrombolysis In Myocardial Infarction; and VA, Veterans Affairs. Appendix 3. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational or Other Financial Benefit Expert Witness


CLINICAL GUIDELINES American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy Daniel M. Witt,1 Nathan P. Clark,3 Mark A. Crowther,11 John J. Riva,2,14 and Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT; 2 Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada; 3 Clinical Pharmacy Anticoagulation and Anemia Service, Kaiser Permanente Colorado, Aurora, CO; 4 School of Medicine, Hofstra Northwell, Hempstead, NY; 5 Division of Clinical Pharmacology and Toxicology, Department of Medicine, McMaster University, Hamilton, ON, Canada; 6 Unit for Health Promotion Research, Department of Public Health, University of Southern Denmark, Esbjerg, Denmark; 7 Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, GA; 8 Aurora Medical Center Summit, Summit, WI; 9 Cambridge, ON, Canada; 10 Department of Medicine and Surgery, Insubria University, Varese, Italy; 11 Department of Medicine, McMaster University, Hamilton, ON, Canada; 12 Department of Medicine, University of Toronto, Toronto, ON, Canada; Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL; and 14 Department of Family Medicine, McMaster University, Hamilton, ON, Canada Background: Clinicians confront numerous practical issues in optimizing the use of anticoagulants to treat venous thromboembolism (VTE). Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in their decisions about the use of anticoagulants in the management of VTE. These guidelines assume the choice of anticoagulant has already been made. Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients.


The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 25 recommendations and 2 good practice statements to optimize management of patients receiving anticoagulants. Conclusions: Strong recommendations included using patient self-management of international normalized ratio (INR) with home point-of-care INR monitoring for vitamin K antagonist therapy and against using periprocedural low-molecular-weight heparin (LMWH) bridging therapy. Conditional recommendations included basing treatment dosing of LMWH on actual body weight, not using anti factor Xa monitoring to guide LMWH dosing, using specialized anticoagulation management services, and resuming anticoagulation after episodes of life-threatening bleeding. Summary of recommendations Anticoagulant therapy is complex and associated with both substantial benefits (reduced risk for thrombus extension and fatal pulmonary embolism [PE] in the setting of acute illness and recurrent venous thromboembolism [VTE] thereafter) and risks (life-threatening bleeding complications).1 Recognizing and mitigating risk for harm from anticoagulants requires an evidence-based approach to anticoagulant management and patient education. These guidelines focus on the optimal management of anticoagulant drugs for the prevention and treatment of VTE following the choice of an anticoagulant. Key management strategies for optimal use of anticoagulants include initial anticoagulant dose selection bloodadvances.2018024893. Resources for implementing these guidelines, including apps, patient decision aids, and teaching slide sets, may be accessed at the ASH web page hematology.org/vte. The full-text version of this article contains a data supplement.


The full-text version of this article contains a data supplement. (recommendation 1), drug-interaction management (recommen- dation 2), point-of-care international normalized ratio (INR) testing (recommendations 3 and 4), INR recall interval selection (recommen- dations 5 and 6), laboratory monitoring of the anticoagulant response (recommendations 7-9), transitions between anticoagulants (recom- mendation 10), the use of specialized anticoagulation-management services (AMSs) (recommendation 11), structured patient education (recommendation 12), efforts to improve adherence to anticoagulant- medication regimens (recommendations 13a-d), invasive procedure management (recommendations 14 and 15), excessive anticoagulation and bleeding management (recommendations 16, 17, 18a and b, 19, and 20), anticoagulant resumption following bleeding (recommendation 21), and renal function monitoring (good practice statements). These guidelines are based on updated and original systematic reviews of evidence developed under the direction of the McMaster University GRADE Centre. The panel followed best practice for guideline development recommended by the Institute of Medicine and the Guidelines International Network.2-5 The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach6-12 to assess certainty in evidence and formulate recommendations. Interpretation of strong and conditional recommendations The strength of a recommendation is expressed as either strong ( the guideline panel recommends ), or conditional ( the guideline panel suggests ) and has the following interpretations. Strong recommendation c For patients: Most individuals in this situation would want the recommended course of action, and only a small proportion would not. c For clinicians: Most individuals should follow the recommended course of action. Formal decision aids are not likely to be needed to help individual patients make decisions consistent with their values and preferences. c For policy makers: The recommendation can be adopted as policy in most situations. Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator.


Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator. c For researchers: The recommendation is supported by credible research or other convincing judgments that make additional research unlikely to alter the recommendation. On occasion, a strong recommendation is based on low or very low certainty in the evidence. In such instances, further research may provide important information that alters the recommendations. Conditional recommendation c For patients: The majority of individuals in this situation would want the suggested course of action, but many would not. Decision aids may be useful in helping patients to make decisions consistent with their individual risks, values, and preferences. c For clinicians: Different choices will be appropriate for individual patients, and clinicians must help each patient arrive at a management decision consistent with the patient s values and preferences. Decision aids may be useful in helping individuals to make decisions consistent with their individual risks, values, and preferences. c For policy makers: Policy-making will require substantial debate and involvement of various stakeholders. Performance measures should assess whether decision-making is duly documented. c For researchers: This recommendation is likely to be strength- ened (for future updates or adaptation) by additional research. An evaluation of the conditions and criteria (and the related judgments, research evidence, and additional considerations) that determined the conditional (rather than strong) recom- mendation will help identify possible research gaps. Recommendations Initial anticoagulant dose selection Recommendation 1. In obese patients receiving low-molecular- weight heparin (LMWH) therapy for treatment of acute VTE, the American Society of Hematology (ASH) guideline panel suggests initial LMWH dose selection according to actual body weight rather than dose selection based on a fixed maximum daily dose (ie, capped dose) (conditional recommendation based on very low certainty in the evidence about effects ).


In obese patients receiving low-molecular- weight heparin (LMWH) therapy for treatment of acute VTE, the American Society of Hematology (ASH) guideline panel suggests initial LMWH dose selection according to actual body weight rather than dose selection based on a fixed maximum daily dose (ie, capped dose) (conditional recommendation based on very low certainty in the evidence about effects ). Drug-interaction management Recommendation 2. For patients requiring administration of inhibitors or inducers of P-glycoprotein (P-gp) or strong inhibitors or inducers of cytochrome P450 (CYP) enzymes, the ASH guideline panel suggests using an alternative anticoagulant (such as vitamin K antagonist [VKA] or LMWH) rather than a direct oral anticoagulant (DOAC) for the treatment of VTE (conditional recommendation based on very low certainty in the evidence about effects ). Point-of-care INR testing Recommendation 3. For patients receiving maintenance VKA therapy for treatment of VTE, the ASH guideline panel suggests using home point-of-care INR testing (patient self-testing [PST]) over any other INR testing approach except patient self- management (PSM) (see recommendation 4) in suitable patients (those who have demonstrated competency to perform PST and who can afford this option) (conditional recommendation based on low certainty in the evidence about effects ). Recommendation 4. For patients receiving maintenance VKA therapy for treatment of VTE, the ASH guideline panel recom- mends using point-of-care INR testing by the patient at home and self-adjustment of VKA dose (PSM) over any other management approach, including PST in suitable patients (those who have demonstrated competency to perform PSM and who can afford this option) (strong recommendation based on low certainty in the evidence about effects ). Selecting the timing between INR measurements (INR recall interval) Recommendation 5.


Selecting the timing between INR measurements (INR recall interval) Recommendation 5. For patients receiving VKA therapy for treatment of VTE, the ASH guideline panel suggests using an INR recall interval of 4 weeks or fewer rather than intervals longer than 4 weeks following VKA dose adjustment due to an out-of-target- range INR (conditional recommendation based on very low certainty in the evidence about effects ). Recommendation 6. For patients receiving maintenance VKA therapy for treatment of VTE, the ASH guideline panel suggests using a longer (6-12 weeks) INR recall interval rather than a shorter (4 weeks) INR recall interval during periods of stable INR control (conditional recommendation based on very low certainty in the evidence about effects ). Laboratory monitoring of the anticoagulant response Recommendation 7. For patients with renal dysfunction (creatinine clearance, ,30 mL/min) receiving LMWH therapy for treatment of VTE, the ASH guideline panel suggests against using anti factor Xa concentration monitoring to guide LMWH dose adjustment (conditional recommendation based on very low certainty in the evidence about effects ). Remark: Instead of monitoring anti factor Xa concentrations, providers should con- sider using doses adjusted for renal function as recommended in product labeling (eg, enoxaparin) or switching to an alternative anticoagulant with lower renal clearance, such as unfractionated heparin (UFH) or a different LMWH. Recommendation 8. For patients with obesity receiving LMWH therapy for treatment of VTE, the ASH guideline panel suggests against using anti factor Xa concentration monitoring to guide LMWH dose adjustment (conditional recommendation based on very low certainty in the evidence about effects ). Remark: Providers should consider LMWH using doses based on actual body weight (see recommendation 1) and not monitoring anti factor Xa concentrations, similar to the approach used in nonobese patients. Recommendation 9.


Remark: Providers should consider LMWH using doses based on actual body weight (see recommendation 1) and not monitoring anti factor Xa concentrations, similar to the approach used in nonobese patients. Recommendation 9. For patients receiving DOAC therapy for the treatment of VTE, the ASH guideline panel suggests against measuring the DOAC anticoagulant effect during management of bleeding (conditional recommendation based on very low certainty in the evidence about effects ). Transitions between anticoagulants Recommendation 10. For patients transitioning from DOAC to VKA, the ASH guideline panel suggests overlapping DOAC and VKA therapy until the INR is within the therapeutic range over using LMWH or UFH bridging therapy (conditional recommen- dation based on very low certainty in the evidence about effects ). Use of specialized AMSs Recommendation 11. For patients receiving anticoagulation therapy for treatment of VTE, the ASH guideline panel suggests using specialized AMS care rather than care provided by the patient s usual health care provider (conditional recommendation based on very low certainty in the evidence about effects ). Structured patient education Recommendation 12. For patients receiving oral anticoagula- tion therapy for VTE treatment, the ASH guideline panel suggests using supplementary patient education in addition to basic education (conditional recommendation based on very low certainty in the evidence about effects ). Efforts to improve anticoagulant-medication adherence Recommendation 13a. For patients receiving anticoagula- tion therapy for treatment of VTE, the ASH guideline panel suggests against using a daily lottery (between a 1-in-5 and 1-in- 100 chance of a monetary reward each day if a pill compartment on a sophisticated electronic-medication-monitoring system is accessed) to improve medication adherence (conditional rec- ommendation based on very low certainty in the evidence about effects ). Recommendation 13b.


For patients receiving anticoagula- tion therapy for treatment of VTE, the ASH guideline panel suggests against using a daily lottery (between a 1-in-5 and 1-in- 100 chance of a monetary reward each day if a pill compartment on a sophisticated electronic-medication-monitoring system is accessed) to improve medication adherence (conditional rec- ommendation based on very low certainty in the evidence about effects ). Recommendation 13b. For patients receiving anticoagulation therapy for treatment of VTE, the ASH guideline panel suggests against using electronic reminders (daily alarm via an electronic- medication-monitoring system) to improve medication adherence (conditional recommendation based on very low certainty in the evidence about effects ). Remark: This recommendation applies specifically to a sophisticated alert system used in the study evaluated by the panel. Recommendation 13c. For patients receiving anticoagula- tion therapy for treatment of VTE, the ASH guideline panel recommends against using a daily lottery (see recommendation 13a) plus electronic reminders (see recommendation 13b) to improve medication adherence (strong recommendation based on very low certainty in the evidence about effects ). Remark: This recommendation applies specifically to a sophisticated alert system used in the study evaluated by the panel. Recommendation 13d. For patients receiving anticoagula- tion therapy for treatment of VTE, the ASH guideline panel suggests against using visual medication schedules (pro- vided to patients at each visit, along with brief counseling) to improve medication adherence (conditional recommendation based on very low certainty in the evidence about effects ). Invasive procedure management Recommendation 14. For patients at low to moderate risk of recurrent VTE who require interruption of VKA therapy for invasive procedures, the ASH guideline panel recommends against periprocedural bridging with LMWH or UHF in favor of interruption of VKA alone (strong recommendation based on moderate certainty in the evidence about effects ). Recommendation 15.


For patients at low to moderate risk of recurrent VTE who require interruption of VKA therapy for invasive procedures, the ASH guideline panel recommends against periprocedural bridging with LMWH or UHF in favor of interruption of VKA alone (strong recommendation based on moderate certainty in the evidence about effects ). Recommendation 15. For patients interrupting DOAC therapy for scheduled invasive procedures, the ASH guideline panel suggests against performing laboratory testing for DOAC anticoagulant effect prior to procedures (conditional recom- mendation based on very low certainty in the evidence about effects ). Excessive anticoagulation and bleeding management Recommendation 16. For patients receiving VKA for treatment of VTE with INRs of .4.5 but ,10 and without clinically relevant bleeding, the ASH guideline panel suggests using temporary cessation of VKA alone without the addition of vitamin K (conditional recommendation based on very low certainty in the evidence about effects ). 27 NOVEMBER 2018 x VOLUME 2, NUMBER 22 ASH 2018 VTE GUIDELINES: ANTICOAGULATION MANAGEMENT 3259 Recommendation 17. For patients with life-threatening bleed- ing during VKA treatment of VTE who have an elevated INR, the ASH guideline panel suggests using 4-factor prothrombin complex concentrates (PCCs) rather than fresh-frozen plasma (FFP) as an addition to cessation of VKA and IV vitamin K (conditional recommendation based on very low certainty in the evidence about effects ). Recommendation 18a. For patients with life-threatening bleed- ing during oral direct Xa inhibitor treatment of VTE, the ASH guideline panel suggests using either 4-factor PCC administration as an addition to cessation of oral direct Xa inhibitor or cessation of oral direct Xa inhibitor alone (conditional recommendation based on very low certainty in the evidence about effects ). Remark: This recommendation does not apply to non life-threatening bleeding.