Examples of Telehealth Strategies and Technologies to Promote Effective Hypertension Management Telehealth strategies Automated BP data capture and transmission of the patient s self- measured BP Self-management support, including education, reminders, and feedback that is automated or delivered by a healthcare professional Medication titration and follow-up monitoring protocols/algorithm Prescription refill reminders Medication adherence assessments Self-monitoring of lifestyle behaviors Integration of behavior change techniques, including in-person counseling or e-counseling Case/care/population health management Commonly used telehealth technologies Wired landline telephone Wireless smartphone applications Website accessed via computers and handheld devices Text messaging Email messaging Social networking and social media websites/applications Wireless BP measurement devices Electronic pill dispensers/counters Reproduced with permission from Whelton et al.4 Copyright 2018, American Heart Association, Inc., and American College of Cardiology Foundation. BP indicates blood pressure. Appendix A. Continued Table C: Procedures for Use of HBPM Patient training should occur under medical supervision, including: Information about hypertension Selection of equipment Acknowledgment that individual BP readings may vary substantially Interpretation of results Devices: Verify use of automated validated devices. Use of auscultatory devices (mercury, aneroid, or other) is not generally useful for HBPM because patients rarely master the technique required for measurement of BP with auscultatory devices. Monitors with provision for storage of readings in memory are preferred. Verify use of appropriate cuff size to fit the arm. Verify that left/right inter-arm differences are insignificant. If differences are significant, instruct patient to measure BPs in the arm with higher readings. Instructions on HBPM procedures: Remain still: Avoid smoking, caffeinated beverages, or exercise within 30 min before BP measurements. Ensure 5 min of quiet rest before BP measurements. Sit correctly: Sit with back straight and supported (on a straight-backed dining chair, for example, rather than a sofa). Sit with feet flat on the floor and legs uncrossed.


Sit with feet flat on the floor and legs uncrossed. Keep arm supported on a flat surface (such as a table), with the upper arm at heart level. Bottom of the cuff should be placed directly above the antecubital fossa (bend of the elbow). Take multiple readings: Take at least 2 readings 1 min apart in morning before taking medications and in evening before supper. Optimally, measure and record BP daily. Ideally, obtain weekly BP readings beginning 2 wk after a change in the treatment regimen and during the week before a clinic visit. Record all readings accurately: Monitors with built-in memory should be brought to all clinic appointments. BP should be based on an average of readings on 2 occasions for clinical decision making. The information above may be reinforced with the following: AHA webpage Monitoring Your Pressure at Home 217 and AHA video At home blood pressure monitoring 218 Reproduced with permission from Whelton et al.4 Copyright 2018, American Heart Association, Inc., and American College of Cardiology Foundation. BP indicates blood pressure; and HBPM, home blood pressure monitoring. Appendix A. Continued 44 SM-9: Use of a Single, Standardized Plan of Care for All Patients With HBP Measure Components The CDU has developed and implemented a single, standardized plan of care for HBP that addresses health behaviors, comorbid conditions, follow-up, and treatment goals through shared decision making, in accordance with Table D. Rationale A specific plan of care for hypertension is essential and should reflect understanding of the modifiable and nonmodifiable determinants of health behaviors, including the social determinants of risk and outcomes. A clinician s sequential flow chart for management of hypertension is presented (Table D). The determinants will vary among demographic subgroups.


A clinician s sequential flow chart for management of hypertension is presented (Table D). The determinants will vary among demographic subgroups. Studies demonstrate that implementation of a plan of care for hypertension can lead to sustained reduction of BP and attainment of BP targets over several Meta-analysis of RCTs shows reductions in BP of patients with hypertension and achievement of BP goals at 6 months and 1 year when compared with usual care.4 (See Table D.) Clinical Recommendations 2017 Hypertension Clinical Practice Guidelines4 The Plan of Care for Hypertension (Guideline Section 13) Every adult with hypertension should have a clear, detailed, and current evidence-based plan of care that ensures the achievement of treatment and self-management goals, encourages effective management of comorbid conditions, prompts timely follow-up with the healthcare team, and adheres to CVD GDMT. (Class 1, Level of Evidence: C-EO) ACC indicates American College of Cardiology; AHA, American Heart Association; BP, blood pressure; CDU, care delivery unit; CVD, cardiovascular disease; GDMT, guideline-directed medical therapy/treatment; HBP, high blood pressure; and RCTs, randomized controlled trials. Appendix A.


(Class 1, Level of Evidence: C-EO) ACC indicates American College of Cardiology; AHA, American Heart Association; BP, blood pressure; CDU, care delivery unit; CVD, cardiovascular disease; GDMT, guideline-directed medical therapy/treatment; HBP, high blood pressure; and RCTs, randomized controlled trials. Appendix A. Continued Table D. Clinician s Steps for the Management of Hypertension Clinician s Sequential Flowchart for the Management of Hypertension Measure office BP accurately Detect white-coat hypertension or masked hypertension by using ABPM and HBPM Evaluate for secondary hypertension Identify target-organ damage Introduce lifestyle interventions Identify and discuss treatment goals Use ASCVD risk estimation to guide BP threshold for pharmacological therapy Align treatment options with comorbidities Account for age, race, ethnicity, sex, and special circumstances in antihypertensive treatment Initiate antihypertensive pharmacological therapy Insure appropriate follow-up Use team-based care Connect patient to clinician via telehealth Detect and reverse nonadherence Use health information technology for remote monitoring and self- monitoring of BP Reproduced with permission from Whelton et al.4 Copyright 2018, American Heart Association, Inc., and American College of Cardiology Foundation. ABPM indicates ambulatory blood pressure monitoring; ASCVD, atherosclerotic cardiovascular disease; BP, blood pressure; and HBPM, home blood pressure monitoring. Appendix A. Continued 45 Use of Performance Measures to Improve Care for HBP SM-10: Use of Performance and Quality Measures to Improve Quality of Care for Patients With HBP Measure Components The CDU uses performance and quality measures for evaluation and improvement in clinical settings for the diagnosis and management of patients with HBP, which include: Performance measures that are developed according to established ACC/AHA standards. Performance measures that identify key structural components, care processes, and/or outcomes that are highly correlated with important, high-priority patient care goals. Methods to accurately and feasibly collect data in order to assess performance measures.


Methods to accurately and feasibly collect data in order to assess performance measures. Process to identify appropriate patient groups, healthcare providers, and/or observation periods to be included in the measurement process. Process to include outcomes of performance measurement in quality improvement strategies. Rationale Performance measures are systematic and standardized methods that are aimed at identifying and improving suboptimal medical care and patient outcomes. Performance measures represent one of several potential strategies that can be used, together or alone, to help reduce gaps in the quality of health care. Effective performance measures are those that are associated with meaningful, desirable patient outcomes and include broad sampling from appropriate and related medical domains.2 Performance measure design should follow established standards, as outlined by national organizations,2 and have precise, validated components that are feasible, actionable, and meaningful. Performance measures usually reflect clinical practice guidelines of the highest levels of recommendation and evidence. Given that the identification, treatment, and control of HBP are suboptimal,3,225,226 use of effective performance measures can help improve these gaps in care, as has been shown in 1 observational study from Kaiser Permanente of Northern California.56 No RCTs of HBP performance measures have been published.4 Implementation of Performance Measures 1. Identify performances measures for hypertension that: a. Meet established ACC/AHA standards. b. Include key components that influence the impact and sustainability of hypertension detection, treatment, and control for the target population (medical care, cost of care, patient-reported factors). c. Help address the most pressing gaps in hypertension-related care for the healthcare provider, practice, or system. Coordinate the most feasible and meaningful collection of performance measures data with available data sources (eg, electronic health records, national data registries, administrative databases).


Coordinate the most feasible and meaningful collection of performance measures data with available data sources (eg, electronic health records, national data registries, administrative databases). Uses of Performance Measures To assess performance of the healthcare provider, practice, or system, identifying and characterizing gaps in quality of hypertension care (based on comparison to a national benchmark standard or based on comparison to previous performance by the same healthcare provider, practice, or system). 2. To be used to design and implement quality improvement plans to help address gaps in quality of hypertension care identified by performance measures. To report the use and outcomes of performance measurement as part of healthcare quality payment programs that are used by organizations to determine reimbursement to healthcare providers, practices, and systems on the basis of achievement and reporting of various performance metrics. Clinical Recommendations 2017 Hypertension Clinical Practice Guidelines4 Recommendation for Performance Measures (Guideline Section 12.4.1) Use of performance measures in combination with other quality improvement strategies at patient-, provider-, and system-based levels is reasonable to facilitate optimal hypertension control.56,227,228 (Class 2a, Level of Evidence: B-NR) ACC indicates American College of Cardiology; AHA, American Heart Association; CDU, care delivery unit; HBP, high blood pressure; and RCT, randomized controlled trial. Appendix A. Continued 46 Appendix B.


Clinical Recommendations 2017 Hypertension Clinical Practice Guidelines4 Recommendation for Performance Measures (Guideline Section 12.4.1) Use of performance measures in combination with other quality improvement strategies at patient-, provider-, and system-based levels is reasonable to facilitate optimal hypertension control.56,227,228 (Class 2a, Level of Evidence: B-NR) ACC indicates American College of Cardiology; AHA, American Heart Association; CDU, care delivery unit; HBP, high blood pressure; and RCT, randomized controlled trial. Appendix A. Continued 46 Appendix B. Author Listing of Relationships With Industry and Other Entities (Relevant) 2019 AHA/ACC Clinical Performance and Quality Measures for Adults With High Blood Pressure Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Donald E. Casey Jr, Chair Thomas Jefferson College of Population Health Adjunct Faculty; Rush Medical College Faculty; University of Minnesota, Institute of Health Informatics Affiliate Faculty; President, American College of Medical Quality; IPO 4 Health Principal and Founder None None None None None None Randal J. Thomas, Vice Chair Mayo Clinic Medical Director, Cardiac Rehabilitation Program None None None None None None Vivek Bhalla Stanford University Medical Center Assistant Professor of Medicine, Nephrology; Stanford Hypertension Center Director Relypsa, Inc. None None None PyrAmes Health None Yvonne Commodore- Mensah Johns Hopkins School of Nursing Assistant Professor None None None None None None Paul A. Heidenreich Stanford VA Palo Alto Health Care System Professor of Medicine None None None None None None Dhaval Kolte Massachusetts General Hospital and Harvard Medical School International Cardiology Fellow None None None None None None Paul Muntner University of Alabama at Birmingham Professor, Department of Epidemiology None None None None None None Sidney C. Smith Jr University of North Carolina at Chapel Hill Professor of Medicine; Division of Cardiology, Department of Medicine None None None None None None John A. Spertus Washington University School of Medicine in St. Louis Adjunct Professor of Medicine, Cardiovascular Division; Saint Luke s Mid America Heart Institute Director, Health Outcomes Research; University of Missouri-Kansas City Professor, Daniel J. Lauer Missouri Endowed Chair in Metabolism and Vascular Disease Research AstraZeneca* Bayer Healthcare Pharmaceuticals Boehringer Ingelheim* Janssen* Novartis* None None None AstraZeneca UK Limited Novartis* None John R. Windle University of Nebraska College of Medicine Professor, Internal Medicine, Division of Cardiovascular Medicine None None None None None None Gregory D. Wozniak American Medical Association Director, Outcomes Analytics; Northwestern University, Feinberg School of Medicine Adjunct Assistant Professor None None None None None None Boback Ziaeian UCLA David Geffen School of Medicine Assistant Professor; US Department of Veterans Affairs Assistant Professor 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. 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. *Significant relationship. No financial benefit. ACC indicates American College of Cardiology; AHA, American Heart Association; UCLA, University of California, Los Angeles; and VA, Veterans Affairs.


ACC indicates American College of Cardiology; AHA, American Heart Association; UCLA, University of California, Los Angeles; and VA, Veterans Affairs. 47 Appendix C. Reviewer Listing of Relationships With Industry and Other Entities (Comprehensive) 2019 AHA/ACC Clinical Performance and Quality Measures for Adults With High Blood Pressure Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Salary Biykem Bozkurt Official TFPM Lead; TFDS Content Reviewer Baylor College of Medicine Mary and Gordon Cain Chair Professor of Medicine and Director, Winters Center for Heart Failure Research; Michael E. DeBakey VA Medical Center, Cardiology Chief, Cardiology Section Bayer Bristol-Myers Squibb Lantheus Medical Imaging, Inc LivaNova USA Respicardia scPharmaceuticals None None LivaNova USA (DSMB) Abbott None None Nicole L. Lohr Official ACC Medical College of Wisconsin Assistant Professor None None None None Amgen None None Andrea L. Price Official ACC Indiana University Health Director, Quality Databases None None None None ACC Accreditation Foundation Board* None None Brent Egan Official AHA Medical University of South Carolina, Charleston (MUSC) Professor of Medicine and Pharmacology Medtronic Emcure Merck KGaA None None UpToDate None None John M. Flack Official AHA Southern Illinois University School of Medicine, Internal Medicine Professor, Chair, and Chief of Hypertension Specialty Services None None None National Institutes of Health (DSMB) Bayer GlaxoSmithKline Valencia None None Sandra J. Taler Official AHA Mayo Clinic Professor of Medicine None None None None None None None Michael Rakotz Official AMA American Medical Association Vice President, Health Outcomes None None None None AMA None None Cheryl Dennison- Himmelfarb Official PCNA Johns Hopkins School of Nursing Associate Dean for Research, Sarah E. Allison Endowed Professor, and Deputy Director, Institute for Clinical Translational Research None None None Helene Fuld Health Trust* NIH* PCNA None Johns Hopkins University* Nathalie De Michelis Content ACC University of California, Irvine Cardiovascular Program Manager None None None None None None None Eugene Yang Content ACC University of Washington School of Medicine Medical Director and Clinical Associate Professor of Medicine, Division of Cardiology, Carl and Ren e Behnke Endowed Professorship for Asian Health Amgen* RubiconMD* None None None Amgen* Third Party, Firefighter who developed an arrhythmia at work, None Marjorie L. King Content ACC/ AHA Helen Hayes Hospital Chief Medical Officer, Internal Medicine (Cardiology) and Director, Cardiopulmonary, Rehabilitation Island Peer Review Organization* None None None None None None (Continued) 48 Raj Padwal Content AMA University of Alberta Professor of Medicine and Director, Hypertension Dyslipidemia Clinic None None mmHG Inc. None None None None Nancy Houston- Miller Content PCNA The Lifecare Company Associate Director Moving Analytics* None None None None None None This table represents all relationships of reviewers with industry and other entities that were reported 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 reviewer acknowledges that there is no direct or institutional relationship with the trial sponsor as defined in the ACCF or ACC/AHA Disclosure Policy for Writing Committees. ACC indicates American College of Cardiology; AHA, American Heart Association; AMA, American Medical Association; DSMB, Data Safety and Monitoring Board; HBP, high blood pressure; NIH, National Institutes of Health; PCNA, Preventive Cardiovascular Nurses Association; TFDS, Task Force for Data Standards; and TFPM, Task Force on Performance Measures. Appendix C. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Salary


ACC/AHA/HFSA Focused Update Developed in Collaboration With the American College of Chest Physi- cians and International Society for Heart and Lung Transplantation ACC/AHA Task Force Members, see page e287 WRITING COMMITTEE MEMBERS* Clyde W. Yancy, MD, MSc, MACC, FAHA, FHFSA, Chair Mariell Jessup, MD, FACC, FAHA, FESC, Vice Chair Biykem Bozkurt, MD, PhD, FACC, FAHA Javed Butler, MD, MBA, MPH, FACC, FAHA Donald E. Casey, Jr, MD, MPH, MBA, FACC Monica M. Colvin, MD, FAHA Mark H. Drazner, MD, MSc, FACC, FAHA Gerasimos Filippatos, MD, FESC Gregg C. Fonarow, MD, FACC, FAHA, FHFSA Michael M. Givertz, MD, FACC, FHFSA Steven M. Hollenberg, MD, FACC# JoAnn Lindenfeld, MD, FACC, FAHA, FHFSA Frederick A. Masoudi, MD, MSPH, FACC** Patrick E. McBride, MD, MPH, FACC Pamela N. Peterson, MD, FACC Lynne Warner Stevenson, MD, FACC Cheryl Westlake, PhD, RN, ACNS-BC, FHFSA 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America Key Words: AHA Scientific Statements angioedema angiotensin-converting enzyme inhibitors angiotensin receptor blockers angiotensin receptor- neprilysin inhibitor beta blockers focused update heart failure ivabradine natriuretic peptides 2016 by the American College of Cardiology Foundation, the American Heart Association, Inc., and the Heart Failure Society of America.


The American Heart Association requests that this document be cited as follows: Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Colvin MM, Drazner MH, Filippatos G, Fonarow GC, Givertz MM, Hollenberg SM, Lindenfeld J, Masoudi FA, McBride PE, Peterson PN, Stevenson LW, Westlake C. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation. 2016;134:e282 e293. DOI: 10.1161/CIR.0000000000000435. *Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry may apply; see Appendix 1 for detailed information. ACC/AHA Task Force on Clinical Practice Guidelines Liaison. ACC/AHA Representative. ACP Representative. ISHLT Representative. HFSA Representative. #CHEST Representative. **ACC/AHA Task Force on Performance Measures Representative. AAFP Representative. Heart Failure Focused Update on Pharmacological Therapy CLINICAL STATEMENTS AND GUIDELINES Table of Contents Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e283 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e285 7.3. Stage C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e285 Pharmacological Treatment for Stage C HF With Reduced Ejection Fraction: Recommendations e285 Renin-Angiotensin System Inhibition With Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker or ARNI: Recommendations . .


e285 Pharmacological Treatment for Stage C HF With Reduced Ejection Fraction: Recommendations e285 Renin-Angiotensin System Inhibition With Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker or ARNI: Recommendations . . e285 Ivabradine: Recommendation . . . . . . . e287 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e288 Appendix 1. Author Relationships With Industry and Other Entities (Relevant) . . . . . . . . . . . e289 Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive) . . . . . . e291 Preamble Incorporation of new study results, medications, or de- vices that merit modification of existing clinical practice guideline recommendations, or the addition of new rec- ommendations, is critical to ensuring that guidelines re- flect current knowledge, available treatment options, and optimum medical care. To keep pace with evolving evi- dence, the American College of Cardiology (ACC)/Ameri- can Heart Association (AHA) Task Force on Clinical Prac- tice Guidelines ( Task Force ) has issued this focused update to reassess guideline recommendations on the basis of recently published study data. This update 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 Processes have evolved over time in response to pub- lished reports from the Institute of Medicine2,3 and ACC/ leading to adoption of a knowledge byte format. This process entails delineation of a rec- ommendation addressing a specific clinical question, followed by concise text (ideally <250 words) and hy- perlinked to supportive evidence.


This process entails delineation of a rec- ommendation addressing a specific clinical question, followed by concise text (ideally <250 words) and hy- perlinked to supportive evidence. This approach better accommodates time constraints on busy clinicians, facil- itates easier access to recommendations via electronic search engines and other evolving technology, and sup- ports the evolution of guidelines as living documents that can be dynamically updated as needed. Guideline-Directed Evaluation and Management The term guideline-directed evaluation and management (GDEM) refers to care defined mainly by ACC/AHA Class I recommendations. For these and all recommended drug treatment regimens, the reader should confirm dosage with product insert material and carefully evaluate for contraindications and interactions. Recommendations are limited to treatments, drugs, and devices approved for clinical use in the United States. Class of Recommendation and Level of Evidence The Class of Recommendation (COR) and Level of Evi- dence (LOE) are derived independently of each other according to established criteria. The COR indicates the strength of recommendation, encompassing the es- timated magnitude and certainty of benefit of a clinical action in proportion to risk. The LOE rates the quality of scientific evidence supporting the intervention on the basis of the type, quantity, and consistency of data from clinical trials and other sources (Table 1). Recommenda- tions in this focused update reflect the new 2015 COR/ LOE system, in which LOE B and C are subcategorized for the purpose of increased granularity.1,5,8 Relationships With Industry and Other Entities The ACC and AHA exclusively sponsor the work of guide- line writing committees without commercial support, and members volunteer time for this activity. Selected orga- nizations and professional societies with related interests and expertise are invited to participate as partners or collaborators.


Selected orga- nizations and professional societies with related interests and expertise are invited to participate as partners or collaborators. The Task Force makes every effort to avoid actual, potential, or perceived conflicts of interest that might arise through relationships with industry or other entities (RWI). All writing committee members and reviewers are required to fully disclose current industry relationships or personal interests, beginning 12 months before initiation of the writing effort. Management of RWI involves selecting a balanced writing committee and re- quires that both the chair and a majority of writing com- mittee members have no relevant RWI (see Appendix 1 for the definition of relevance). Members are restricted with regard to writing or voting on sections to which RWI apply. Members of the writing committee who recused themselves from voting are indicated and specific section recusals are noted in Appendix 1. In addition, for transpar- ency, members comprehensive disclosure information is available as an Online Supplement, and reviewers RWI disclosures are included in Appendix 2. Comprehensive disclosure information for the Task Force is also avail- able at http://www.acc.org/guidelines/about-guidelines- and-clinical-documents/guidelines-and-documents-task- forces. The Task Force strives to avoid bias by selecting experts from a broad array of backgrounds representing different geographic regions, genders, ethnicities, intel- lectual perspectives, and scopes of clinical activities. Intended Use Guidelines provide recommendations applicable to pa- tients with or at risk of developing cardiovascular disease. The focus is on medical practice in the United States, but guidelines developed in collaboration with other organiza- tions may have a broader target. Although guidelines may Yancy et al be used to inform regulatory or payer decisions, the intent is to improve quality of care and align with patients inter- ests. The guidelines are reviewed annually by the Task Force and are official policy of the ACC and AHA.


The guidelines are reviewed annually by the Task Force and are official policy of the ACC and AHA. Each guideline is considered current unless and until it is up- dated, revised, or superseded by a published addendum. Related Issues For additional information pertaining to the methodology for grading evidence, assessment of benefit and harm, shared decision making between the patient and cli- nician, structure of evidence tables and summaries, standardized terminology for articulating recommen- dations, organizational involvement, peer review, and policies regarding periodic assessment and up- dating of guideline documents, we encourage read- ers to consult the ACC/AHA guideline methodology Jonathan L. Halperin, MD, FACC, FAHA Chair, ACC/AHA Task Force on Clinical Practice Guidelines Table 1. Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated August 2015) Heart Failure Focused Update on Pharmacological Therapy CLINICAL STATEMENTS AND GUIDELINES Introduction The ACC, the AHA, and the Heart Failure Society of America (HFSA) recognize that the introduction of effec- tive new therapies that potentially affect a large number of patients presents both opportunities and challenges. The introduction of an angiotensin receptor neprilysin inhibitor (ARNI) (valsartan/sacubitril) and a sinoatrial node modulator (ivabradine), when applied judiciously, complements established pharmacological and device- based therapies and represents a milestone in the evolu- tion of care for patients with heart failure (HF). Accord- ingly, the writing committees of the 2016 ACC/AHA/ HFSA Focused Update on New Pharmacological Therapy for Heart Failure and the 2016 ESC Guideline on the Diagnosis and Treatment of Acute and Chronic Heart Failure concurrently developed recommendations for the incorporation of these therapies into clinical prac- tice. Working independently, each writing committee sur- veyed the evidence, arrived at similar conclusions, and constructed similar, but not identical, recommendations.


Working independently, each writing committee sur- veyed the evidence, arrived at similar conclusions, and constructed similar, but not identical, recommendations. Given the concordance, the respective organizations si- multaneously issued aligned recommendations on the use of these new treatments to minimize confusion and improve the care of patients with HF. Members of the ACC/AHA/HFSA writing committee without relevant RWI voted on the final recommendations. These were subjected to external peer review by 25 official, organizational, and content reviewers before ap- proval by the Task Force and the leadership of the ACC, AHA, and HFSA, as well as endorsement by the American College of Chest Physicians and the International Society for Heart and Lung Transplantation. The statements is- sued by the European Society of Cardiology writing com- mittee went through a similarly rigorous process of exter- nal review before endorsement by the societal leadership. No single clinical trial answers all pertinent questions, nor can trial results be perfectly replicated in clinical practice. Several critical questions remain unanswered, and further experience in both ongoing trials and clinical therapeutics may require modification of these initial rec- ommendations. On the basis of the currently available evidence, however, the recommendations that follow reflect our assessment of how best to proceed today. 7.3. Stage C 7.3.2. Pharmacological Treatment for Stage C HF With Reduced Ejection Fraction: Recommendations 7.3.2.10. Renin-Angiotensin System Inhibition With Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker or ARNI: Recommendations See the Online Data Supplement for evidence supporting these recommendations.


Renin-Angiotensin System Inhibition With Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker or ARNI: Recommendations See the Online Data Supplement for evidence supporting these recommendations. Recommendations for Renin-Angiotensin System Inhibition With ACE Inhibitor or ARB or ARNI COR LOE Recommendations I ACE: A The clinical strategy of inhibition of the renin-angiotensin system with ACE inhibitors (Level of Evidence: OR ARBs (Level of Evidence: A),15 18 OR ARNI (Level of Evidence: B-R)19 in conjunction with evidence- based beta blockers,20 22 and aldosterone antagonists in selected patients,23,24 is recommended for patients with chronic HFrEF to reduce morbidity and mortality. ARB: A ARNI: B-R See Online Data 18 20. Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity and mortality in heart failure with reduced ejection fraction (HFrEF). Randomized controlled trials (RCTs) clearly establish the benefits of ACE inhibition in patients with mild, moderate, or severe symptoms of HF and in patients with or without coronary artery disease.9 14 ACE inhibitors can produce angioedema and should be given with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium. ACE inhibitors also inhibit kininase and increase levels of bradykinin, which can induce cough but also may contribute to their beneficial effect through vasodilation. Angiotensin receptor blockers (ARBs) were developed with the rationale that angiotensin II production continues in the presence of ACE inhibition, driven through alternative enzyme pathways.ARBs do not inhibit kininase and are associated with a much lower incidence of cough and angioedema than ACE inhibitors; but like ACE inhibitors,ARBs should be given with caution to patients with low systemic blood pressure, renal insufficiency, or elevated serum potassium.


Angiotensin receptor blockers (ARBs) were developed with the rationale that angiotensin II production continues in the presence of ACE inhibition, driven through alternative enzyme pathways.ARBs do not inhibit kininase and are associated with a much lower incidence of cough and angioedema than ACE inhibitors; but like ACE inhibitors,ARBs should be given with caution to patients with low systemic blood pressure, renal insufficiency, or elevated serum potassium. Long-term therapy with ARBs produces hemodynamic, neurohormonal, and clinical effects consistent with those expected after interference with the renin-angiotensin system and have been shown in RCTs15 18 to reduce morbidity and mortality, especially in ACE inhibitor intolerant patients. In ARNI, an ARB is combined with an inhibitor of neprilysin, an enzyme that degrades natriuretic peptides, bradykinin, adrenomedullin, and other vasoactive peptides. In an RCT that compared the first approved ARNI, valsartan/sacubitril, with enalapril in symptomatic patients with HFrEF tolerating an adequate dose of either ACE inhibitor or ARB, the ARNI reduced the composite endpoint of cardiovascular death or HF hospitalization significantly, by 20%.19 The benefit was seen to a similar extent for both death and HF hospitalization and was consistent across subgroups. The use of ARNI is associated with the risk of hypotension and renal insufficiency and may lead to angioedema, as well. I ACE: A The use of ACE inhibitors is beneficial for patients with prior or current symptoms of chronic HFr EF to reduce morbidity and mortality.9 14,25 (Continued) Yancy et al See Online Data Supplement 18.


I ACE: A The use of ACE inhibitors is beneficial for patients with prior or current symptoms of chronic HFr EF to reduce morbidity and mortality.9 14,25 (Continued) Yancy et al See Online Data Supplement 18. ACE inhibitors have been shown in large RCTs to reduce morbidity and mortality in patients with HFrEF with mild, moderate, or severe symptoms of HF, with or without coronary artery disease.9 14 Data suggest that there are no differences among available ACE inhibitors in their effects on symptoms or survival.25 ACE inhibitors should be started at low doses and titrated upward to doses shown to reduce the risk of cardiovascular events in clinical trials. ACE inhibitors can produce angioedema and should be given with caution to patients with low systemic blood pressures, renal insufficiency, or elevated serum potassium (>5.0 mEq/L). Angioedema occurs in <1% of patients who take an ACE inhibitor, but it occurs more frequently in blacks and women.26 Patients should not be given ACE inhibitors if they are pregnant or plan to become pregnant. ACE inhibitors also inhibit kininase and increase levels of bradykinin, which can induce cough in up to 20% of patients but also may contribute to beneficial vasodilation. If maximal doses are not tolerated, intermediate doses should be tried; abrupt withdrawal of ACE inhibition can lead to clinical deterioration and should be avoided. Although the use of an ARNI in lieu of an ACE inhibitor for HFrEF has been found to be superior, for those patients for whom ARNI is not appropriate, continued use of an ACE inhibitor for all classes of HFrEF remains strongly advised.


Although the use of an ARNI in lieu of an ACE inhibitor for HFrEF has been found to be superior, for those patients for whom ARNI is not appropriate, continued use of an ACE inhibitor for all classes of HFrEF remains strongly advised. I ARB: A The use of ARBs to reduce morbidity and mortality is recommended in patients with prior or current symptoms of chronic HFr EF who are intolerant to ACE inhibitors because of cough or angioedema.15 18,27,28 See Online Data and 19. ARBs have been shown to reduce mortality and HF hospitalizations in patients with HFrEF in large RCTs.15 18 Long-term therapy with ARBs in patients with HFrEF produces hemodynamic, neurohormonal, and clinical effects consistent with those expected after interference with the renin-angiotensin system.27,28 Unlike ACE inhibitors, ARBs do not inhibit kininase and are associated with a much lower incidence of cough and angioedema, although kininase inhibition by ACE inhibitors may produce beneficial vasodilatory effects. Patients intolerant to ACE inhibitors because of cough or angioedema should be started on ARBs; patients already tolerating ARBs for other indications may be continued on ARBs if they subsequently develop HF. ARBs should be started at low doses and titrated upward, with an attempt to use doses shown to reduce the risk of cardiovascular events in clinical trials. ARBs should be given with caution to patients with low systemic blood pressure, renal insufficiency, or elevated serum potassium (>5.0 mEq/L). Although ARBs are alternatives for patients with ACE inhibitor induced angioedema, caution is advised because some patients have also developed angioedema with ARBs. Head-to-head comparisons of an ARB versus ARNI for HF do not exist. For those patients for whom an ACE inhibitor or ARNI is inappropriate, use of an ARB remains advised.


For those patients for whom an ACE inhibitor or ARNI is inappropriate, use of an ARB remains advised. I ARNI: B-R In patients with chronic symptomatic HFr EF NYHA class II or III who tolerate an ACE inhibitor or ARB, replacement by an ARNI is recommended to further reduce morbidity and mortality.19 See Online Data and 18. Benefits of ACE inhibitors with regard to decreasing HF progression, hospitalizations, and mortality rate have been shown consistently for patients across the clinical spectrum, from asymptomatic to severely symptomatic HF. Similar benefits have been shown for ARBs in populations with mild-to-moderate HF who are unable to tolerate ACE inhibitors. In patients with mild-to-moderate HF (characterized by either 1) mildly elevated natriuretic peptide levels, BNP [B-type natriuretic peptide] >150 pg/mL or NT-proBNP [N-terminal pro-B-type natriuretic peptide] 600 pg/mL; or 2) BNP 100 pg/mL or NT-proBNP 400 pg/mL with a prior hospitalization in the preceding 12 months) who were able to tolerate both a target dose of enalapril (10 mg twice daily) and then subsequently an ARNI (valsartan/sacubitril; 200 mg twice daily, with the ARB component equivalent to valsartan 160 mg), hospitalizations and mortality were significantly decreased with the valsartan/sacubitril compound compared with enalapril. The target dose of the ACE inhibitor was consistent with that known to improve outcomes in previous landmark clinical trials.10 This ARNI has recently been approved for patients with symptomatic HFrEF and is intended to be substituted for ACE inhibitors or ARBs. HF effects and potential off-target effects may be complex with inhibition of the neprilysin enzyme, which has multiple biological targets. Use of an ARNI is associated with hypotension and a low-frequency incidence of angioedema.


Use of an ARNI is associated with hypotension and a low-frequency incidence of angioedema. To facilitate initiation and titration, the approved ARNI is available in 3 doses that include a dose that was not tested in the HF trial; the target dose used in the trial was 97/103 mg twice daily.29 Clinical experience will provide further information about the optimal titration and tolerability of ARNI, particularly with regard to blood pressure, adjustment of concomitant HF medications, and the rare complication of angioedema.30 III: Harm B-R ARNI should not be administered concomitantly with ACE inhibitors or within 36 hours of the last dose of an See Online Data Supplement 3. Oral neprilysin inhibitors, used in combination with ACE inhibitors, can lead to angioedema and concomitant use is contraindicated and should be avoided. A medication that represented both a neprilysin inhibitor and an ACE inhibitor, omapatrilat, was studied in both hypertension and HF, but its development was terminated because of an unacceptable incidence of angioedema31,32 and associated significant morbidity. This adverse effect was thought to occur because both ACE and neprilysin break down bradykinin, which directly or indirectly can cause angioedema.32,33 An ARNI should not be administered within 36 hours of switching from or to an ACE inhibitor. Recommendations for Renin-Angiotensin System Inhibition With ACE Inhibitor or ARB or ARNI (Continued) COR LOE Recommendations (Continued) CLINICAL STATEMENTS AND GUIDELINES Heart Failure Focused Update on Pharmacological Therapy 7.3.2.11. Ivabradine: Recommendation See the Online Data Supplement for evidence supporting this recommendation. The remainder of the 2016 ACC/AHA/HFSA Focused Update on the Management of Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure will be forthcoming.


The remainder of the 2016 ACC/AHA/HFSA Focused Update on the Management of Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure will be forthcoming. ACC/AHA TASK FORCE MEMBERS Jonathan L. Halperin, MD, FACC, FAHA, Chair Glenn N. Levine, MD, FACC, FAHA, Chair-Elect 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 Jos Joglar, MD, FACC, FAHA Susan J. Pressler, PhD, RN, FAHA Duminda N. Wijeysundera, MD, PhD Presidents and Staff American College of Cardiology Richard A. Chazal, MD, FACC, 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, Educa- tion, Quality, and Publishing American College of Cardiology/American Heart Association Melanie Stephens-Lyman, MSc, Director, Guideline Operations and Strategy Lisa Bradfield, CAE, Director, Guideline Methodology and Policy Abdul R. Abdullah, MD, Associate Science and Medicine Advisor Recommendation for Ivabradine COR LOE Recommendation IIa B-R Ivabradine can be beneficial to reduce HF hospitalization for patients with symptomatic (NYHA class II-III) stable chronic HFr EF (LVEF 35%) who are receiving GDEM, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of 70 bpm or greater at rest.37 40 See Online Data Supplement 4. Ivabradine is a new therapeutic agent that selectively inhibits the If current in the sinoatrial node, providing heart rate reduction.


Ivabradine is a new therapeutic agent that selectively inhibits the If current in the sinoatrial node, providing heart rate reduction. One RCT demonstrated the efficacy of ivabradine in reducing the composite endpoint of cardiovascular death or HF hospitalization.38 The benefit of ivabradine was driven by a reduction in HF hospitalization. The study included patients with HFrEF (New York Heart Association [NYHA] class II-IV, albeit with only a modest representation of NYHA class IV HF) and left ventricular ejection fraction (LVEF) 35%, in sinus rhythm with a resting heart rate of 70 bpm. Patients enrolled included a small number with paroxysmal atrial fibrillation (<40% of the time) but otherwise in sinus rhythm and a small number experiencing ventricular pacing but with a predominant sinus rhythm. Those with a myocardial infarction within the preceding 2 months were excluded. Patients enrolled had been hospitalized for HF in the preceding 12 months and were on stable GDEM for 4 weeks before initiation of ivabradine therapy. The target of ivabradine is heart rate slowing (the presumed benefit of action), but only 25% of patients studied were on optimal doses of beta-blocker therapy.20 22,38 Given the well-proven mortality benefits of beta-blocker therapy, it is important to initiate and up titrate these agents to target doses, as tolerated, before assessing the resting heart rate for consideration of ivabradine initiation.38 III: Harm C-EO ARNI should not be administered to patients with a history of angioedema. N/A Omapatrilat, a neprilysin inhibitor (as well as an ACE inhibitor and aminopeptidase P inhibitor), was associated with a higher frequency of angioedema than that seen with enalapril in an RCT of patients with HFrEF.31 In a very large RCT of hypertensive patients, ompatrilat was associated with a 3-fold increased risk of angioedema as compared with Blacks and smokers were particularly at risk.


N/A Omapatrilat, a neprilysin inhibitor (as well as an ACE inhibitor and aminopeptidase P inhibitor), was associated with a higher frequency of angioedema than that seen with enalapril in an RCT of patients with HFrEF.31 In a very large RCT of hypertensive patients, ompatrilat was associated with a 3-fold increased risk of angioedema as compared with Blacks and smokers were particularly at risk. The high incidence of angioedema ultimately led to cessation of the clinical development of omapatrilat.34,35 In light of these observations, angioedema was an exclusion criterion in the first large trial assessing ARNI therapy in patients with hypertension36 and then in the large trial that demonstrated clinical benefit of ARNI therapy in HFrEF.19 ARNI therapy should not be administered in patients with a history of angioedema because of the concern that it will increase the risk of a recurrence of angioedema. Recommendations for Renin-Angiotensin System Inhibition With ACE Inhibitor or ARB or ARNI (Continued) COR LOE Recommendations Yancy et al Morgane Cibotti-Sun, MPH, Project Manager, Clinical Practice Guidelines American Heart Association Mark A. Creager, MD, FACC, FAHA, President Nancy Brown, Chief Executive Officer Rose Marie Robertson, MD, FAHA, Chief Science and Medical Officer Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice Presi- dent, Office of Science Operations Comilla Sasson, MD, PhD, FACEP, Vice President, Science and Medicine Jody Hundley, Production Manager, Scientific Publications, Office of Science Operations FOOTNOTES 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 Executive Committee, and the Heart Failure Society of America Executive Committee in April 2016. The Comprehensive RWI Data Supplement table is available with this article at http://circ.ahajournals.org/lookup/suppl/ doi:10.1161/CIR.0000000000000435/-/DC1. The Data Supplement is available with this article at CIR.0000000000000435/-/DC2.


The Data Supplement is available with this article at CIR.0000000000000435/-/DC2. This article has been copublished in the Journal of the American College of Cardiology and the Journal of Cardiac Failure. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org), the American Heart Association (professional.heart.org), and the Heart Failure Society of America (www.hfsa.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 addi- tional 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 state- ments 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. A link to the Copyright Permissions Request Form appears on the right side of the page. Circulation is available at http://circ.ahajournals.org. References 1. ACCF/AHA Task Force on Practice Guidelines. Methodology Manual and Policies From the ACCF/AHA Task Force on Practice Guidelines. Available at: http://assets.cardiosource.com/Method- ology_Manual_for_ACC_AHA_Writing_Committees.pdf and http:// my.americanheart.org/idc/groups/ahamah-public/@wcm/@sop/ College of Cardiology and American Heart Association. Accessed April 7, 2016. 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). Finding What Works in Health Care: Standards for Systematic Reviews. Wash- ington, DC: National Academies Press; 2011. 4. Jacobs AK, Kushner FG, Ettinger SM, et al.


Wash- ington, DC: National Academies Press; 2011. 4. Jacobs AK, Kushner FG, Ettinger SM, et al. ACCF/AHA clinical prac- tice 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. 5. 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. 6. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA state- ment 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 Perfor- mance Measures and Task Force on Practice Guidelines. Circula- tion. 2014;129:2329 45. 7. Arnett DK, Goodman RA, Halperin JL, et al. AHA/ACC/HHS strate- gies to enhance application of clinical practice guidelines in pa- tients with cardiovascular 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. 8. Halperin JL, Levine GN, Al-Khatib SM, et al. Further evolution of the ACC/AHA clinical practice guideline recommendation classi- fication system: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guide- lines. Circulation. 2016;133:1426 28. 9. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med. 1987;316:1429 35. 10. Effect of enalapril on survival in patients with reduced left ven- tricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med. 1991;325:293 302. 11. Packer M, Poole-Wilson PA, Armstrong PW, et al.


1991;325:293 302. 11. Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative ef- fects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart fail- ure. ATLAS Study Group. Circulation. 1999;100:2312 8. 12. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunc- tion after myocardial infarction. Results of the survival and ven- tricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992;327:669 77. 13. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lan- cet. 1993;342:821 8. 14. K ber L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Tran- dolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med. 1995;333:1670 6. 15. Cohn JN, Tognoni G, Valsartan Heart Failure Trial Investigators. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667 75. Heart Failure Focused Update on Pharmacological Therapy CLINICAL STATEMENTS AND GUIDELINES 16. Pfeffer MA, McMurray JJV, Velazquez EJ, et al. Valsartan, capto- pril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med. 2003;349: 1893 906. 17. Konstam MA, Neaton JD, Dickstein K, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lan- cet. 2009;374:1840 8. 18. Pfeffer MA, Swedberg K, Granger CB, et al. Effects of candesar- tan on mortality and morbidity in patients with chronic heart fail- ure: the CHARM-Overall programme. Lancet. 2003;362:759 66. 19. McMurray JJV, Packer M, Desai AS, et al.


2003;362:759 66. 19. McMurray JJV, Packer M, Desai AS, et al. Angiotensin-nepri- lysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993 1004. 20. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353:2001 7. 21. Packer M, Fowler MB, Roecker EB, et al. Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (CO- PERNICUS) study. Circulation. 2002;106:2194 9. 22. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;128:e240 327. 23. Eschalier R, McMurray JJV, Swedberg K, et al. Safety and effi- cacy of eplerenone in patients at high risk for hyperkalemia and/ or worsening renal function: analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIv- al Study in Heart Failure). J Am Coll Cardiol. 2013;62:1585 93. 24. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341:709 17. 25. Garg R, Yusuf S. Overview of randomized trials of angiotensin-con- verting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials. JAMA. 1995;273:1450 6. 26. Woodard-Grice AV, Lucisano AC, Byrd JB, et al. Sex-dependent and race-dependent association of XPNPEP2 C-2399A polymor- phism with angiotensin-converting enzyme inhibitor-associated angioedema. Pharmacogenet Genomics. 2010;20:532 6. 27. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. ONTARGET Investigators. N Engl J Med. 2008;358:1547 59. 28.


Telmisartan, ramipril, or both in patients at high risk for vascular events. ONTARGET Investigators. N Engl J Med. 2008;358:1547 59. 28. Yusuf S, Teo K, Anderson C, et al. Effects of the angiotensin-re- ceptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) Investigators. Lancet. 2008;372:1174 83. 29. Entresto [package insert]. Hanover, NJ: Novartis Pharmaceuticals Corporation; 2015. 30. Solomon SD, Zile M, Pieske B, et al. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejec- tion fraction: a phase 2 double-blind randomised controlled trial. Lancet. 2012;380:1387 95. 31. Packer M, Califf RM, Konstam MA, et al. Comparison of omapa- trilat and enalapril in patients with chronic heart failure: the Omapatrilat Versus Enalapril Randomized Trial of Utility in Reduc- ing Events (OVERTURE). Circulation. 2002;106:920 6. 32. Kostis JB, Packer M, Black HR, et al. Omapatrilat and enala- pril in patients with hypertension: the Omapatrilat Cardiovas- cular Treatment vs. Enalapril (OCTAVE) trial. Am J Hypertens. 2004;17:103 11. 33. Vardeny O, Miller R, Solomon SD. Combined neprilysin and renin- angiotensin system inhibition for the treatment of heart failure. JACC Heart Fail. 2014;2:663 70. 34. Messerli FH, Nussberger J. Vasopeptidase inhibition and angio- oedema. Lancet. 2000;356:608 9. 35. Braunwald E. The path to an angiotensin receptor antagonist-ne- prilysin inhibitor in the treatment of heart failure. J Am Coll Cardiol. 2015;65:1029 41. 36. Ruilope LM, Dukat A, B hm M, et al. Blood-pressure reduction with LCZ696, a novel dual-acting inhibitor of the angiotensin II receptor and neprilysin: a randomised, double-blind, placebo-controlled, ac- tive comparator study. Lancet. 2010;375:1255 66. 37. B hm M, Robertson M, Ford I, et al.


37. B hm M, Robertson M, Ford I, et al. Influence of cardiovascular and noncardiovascular co-morbidities on outcomes and treatment effect of heart rate reduction with ivabradine in stable heart failure (from the SHIFT trial). Am J Cardiol. 2015;116:1890 7. 38. Swedberg K, Komajda M, B hm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010;376:875 85. 39. Fox K, Ford I, Steg PG, et al. Ivabradine in stable coronary artery disease without clinical heart failure. N Engl J Med. 2014;371:1091 9. 40. Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807 16. Appendix 1. Author Relationships With Industry and Other Entities (Relevant) 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure (December 2015) Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals By Section* Clyde W. Yancy, Chair Northwestern University Feinberg School of Medicine, Division of Cardiology Professor of Medicine and Chief; Diversity and Inclusion Vice Dean None None None None None None None Mariell Jessup, Vice Chair University of Pennsylvania Professor of Medicine None None None None None None None Biykem Bozkurt Michael E. DeBakey VA Medical Center The Mary and Gordon Cain Chair and Professor of Medicine None None None Novartis None None 7.3.2.10 and 7.3.2.11. (Continued) Yancy et al Javed Butler Stony Brook University Division Chief of Cardiology Bayer CardioCell Medtronic Merck Novartis Relypsa Takeda Trevena Z Pharma Zensun Novartis None Amgen (DSMB) None None 7.3.2.10 and 7.3.2.11.


(Continued) Yancy et al Javed Butler Stony Brook University Division Chief of Cardiology Bayer CardioCell Medtronic Merck Novartis Relypsa Takeda Trevena Z Pharma Zensun Novartis None Amgen (DSMB) None None 7.3.2.10 and 7.3.2.11. Donald E. Casey, Jr Thomas Jefferson College of Population Health Adjunct Faculty; Alvarez & Marsal IPO4Health Principal and Founder None None None None None None None Monica M. Colvin University of Michigan Associate Professor of Medicine, Cardiology None None None None None None None Mark H. Drazner University of Texas Southwestern Medical Center Professor, Internal Medicine None None Trevena None DCRI/Otsuka UptoDate None None Gerasimos S. Filippatos National and Kapodistrian University of Athens; Attikon University Hospital, Department of Cardiology, Heart Failure Unit Professor of Cardiology None None None Bayer Bayer (DSMB) Novartis Servier Pharmaceuticals Vifor None None 7.3.2.10 and 7.3.2.11. Gregg C. Fonarow Ahmanson-UCLA Cardiomyopathy Center Director; UCLA Division of Cardiology Co-Chief Amgen Janssen Pharmaceuticals Novartis None None Novartis None None 7.3.2.10 and 7.3.2.11. Michael M. Givertz Brigham and Women s Hospital Professor of Medicine Merck Novartis None None None None None 7.3.2.10 and 7.3.2.11. Steven M. Hollenberg Cooper University Hospital Director, Coronary Care Unit, Professor of Medicine None None None None None None None JoAnn Lindenfeld Vanderbilt Heart and Vascular Institute Director, Advanced Heart Failure and Transplant Section Professor of Medicine Abbott Janssen Pharmaceuticals Novartis Relypsa ResMed None None AstraZeneca Novartis None None 7.3.2.10 and 7.3.2.11.


Steven M. Hollenberg Cooper University Hospital Director, Coronary Care Unit, Professor of Medicine None None None None None None None JoAnn Lindenfeld Vanderbilt Heart and Vascular Institute Director, Advanced Heart Failure and Transplant Section Professor of Medicine Abbott Janssen Pharmaceuticals Novartis Relypsa ResMed None None AstraZeneca Novartis None None 7.3.2.10 and 7.3.2.11. Frederick A. Masoudi University of Colorado, Denver Associate Professor of Medicine, Division of Cardiology None None None None None None None Patrick E. McBride University of Wisconsin School of Medicine and Public Health Professor of Medicine and Family Medicine; Associate Director, Preventive Cardiology None None None None None None None Pamela N. Peterson University of Colorado, Denver Health Medical Center Associate Professor of Medicine, Division of Cardiology None None None None None None None Lynne W. Stevenson Brigham and Women s Hospital Cardiovascular Division Director, Cardiomyopathy and Heart Failure Program None None None Novartis PARENT trial (PI) NHLBI INTERMACS (Co PI) None None 7.3.2.10 and 7.3.2.11. 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* (Continued) CLINICAL STATEMENTS AND GUIDELINES Heart Failure Focused Update on Pharmacological Therapy 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* (Continued) CLINICAL STATEMENTS AND GUIDELINES Heart Failure Focused Update on Pharmacological Therapy Appendix 2. Reviewer Relationships With Industry and Other Entities (Comprehensive) 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure (March 2016) Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Kim K. Birtcher Official Reviewer ACC/AHA Task Force on Clinical Practice Guidelines University of Houston College of Pharmacy Clinical Professor Jones & Bartlett Learning None None None None None Akshay S. Desai Official Reviewer HFSA Brigham and Women s Hospital Director, Heart Failure Disease Management, Advanced Heart Disease Section, Cardiovascular Division; Harvard Medical School, Associate Professor of Medicine Medscape Cardiology* Merck Novartis* Relypsa* St. Jude Medical* None None None Novartis* Thoratec None Anita Deswal Official Reviewer AHA Michael E. DeBakey VA Medical Center Associate Chief of Cardiology; Director, Heart Failure Program; Baylor College of Medicine Professor of Medicine None None None NIH* AHA AHA (GWTG Steering Committee) HFSA None Dipti Itchhaporia Official Reviewer ACC Board of Trustees Newport Coast Cardiology Robert and Georgia Roth Endowed Chair for Excellence in Cardiac Care; Director of Disease Management None None None None St. Jude Medical None Ileana L. Pi a Official Reviewer AHA Montefiore Medical Center Associate Chief for Academic Affairs, Cardiology Relypsa None None None None None Geetha Raghuveer Official Reviewer ACC Board of Governors University of Missouri-Kansas City School of Medicine Professor of Pediatrics; Children s Mercy Hospital Pediatric Cardiology None None None None None None (Continued) Cheryl Westlake Azusa Pacific University Professor and Associate Dean, International and Community Programs 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.


Reviewer Relationships With Industry and Other Entities (Comprehensive) 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure (March 2016) Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Kim K. Birtcher Official Reviewer ACC/AHA Task Force on Clinical Practice Guidelines University of Houston College of Pharmacy Clinical Professor Jones & Bartlett Learning None None None None None Akshay S. Desai Official Reviewer HFSA Brigham and Women s Hospital Director, Heart Failure Disease Management, Advanced Heart Disease Section, Cardiovascular Division; Harvard Medical School, Associate Professor of Medicine Medscape Cardiology* Merck Novartis* Relypsa* St. Jude Medical* None None None Novartis* Thoratec None Anita Deswal Official Reviewer AHA Michael E. DeBakey VA Medical Center Associate Chief of Cardiology; Director, Heart Failure Program; Baylor College of Medicine Professor of Medicine None None None NIH* AHA AHA (GWTG Steering Committee) HFSA None Dipti Itchhaporia Official Reviewer ACC Board of Trustees Newport Coast Cardiology Robert and Georgia Roth Endowed Chair for Excellence in Cardiac Care; Director of Disease Management None None None None St. Jude Medical None Ileana L. Pi a Official Reviewer AHA Montefiore Medical Center Associate Chief for Academic Affairs, Cardiology Relypsa None None None None None Geetha Raghuveer Official Reviewer ACC Board of Governors University of Missouri-Kansas City School of Medicine Professor of Pediatrics; Children s Mercy Hospital Pediatric Cardiology None None None None None None (Continued) Cheryl Westlake Azusa Pacific University Professor and Associate Dean, International and Community Programs 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.


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 committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply. Significant relationship.


*Writing committee members are required to recuse themselves from voting on sections to which their specific relationships with industry and other entities may apply. Significant relationship. ACC indicates American College of Cardiology; AHA, American Heart Association; DCRI, Duke Clinical Research Institute; DSMB, data safety monitoring board; HFSA, Heart Failure Society of America; INTERMACS, The Interagency Registry for Mechanically Assisted Circulatory Support; NHLBI, National Heart, Lung, and Blood Institute; PARENT, pulmonary artery pressure reduction with Entresto; and VA, Veterans Affairs. 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* Yancy et al James E. Udelson Official Reviewer HFSA Tufts Medical Center Chief, Division of Cardiology Lantheus Medical Imaging None None Gilead (DSMB) GlaxoSmithKline (DSMB) NHLBI Otsuka Abbott Laboratories (Eligibility Committee) AHA* Circulation/Circulation: Heart Failure HFSA (Executive Council) Pfizer/ GlaxoSmithKline (Clinical Events Committee) Sunshine Heart (Eligibility Committee) None Mary Norine Walsh Official Reviewer ACC Board of Trustees St Vincent Heart Center of Indiana Medical Director, Heart Failure and Cardiac Transplantation None None None None Corvia Medical Otsuka PCORI Thoratec None David A. Baran Organizational Reviewer ISHLT Newark Beth Israel Medical Center Director of Heart Failure and Transplant Research Maquet Otsuka* Novartis None CareDx IMAGE trial (Steering Committee)* NIH* None None Kenneth Casey Organizational Reviewer CHEST Wm.


Continued Committee Member Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness Voting Recusals By Section* Yancy et al James E. Udelson Official Reviewer HFSA Tufts Medical Center Chief, Division of Cardiology Lantheus Medical Imaging None None Gilead (DSMB) GlaxoSmithKline (DSMB) NHLBI Otsuka Abbott Laboratories (Eligibility Committee) AHA* Circulation/Circulation: Heart Failure HFSA (Executive Council) Pfizer/ GlaxoSmithKline (Clinical Events Committee) Sunshine Heart (Eligibility Committee) None Mary Norine Walsh Official Reviewer ACC Board of Trustees St Vincent Heart Center of Indiana Medical Director, Heart Failure and Cardiac Transplantation None None None None Corvia Medical Otsuka PCORI Thoratec None David A. Baran Organizational Reviewer ISHLT Newark Beth Israel Medical Center Director of Heart Failure and Transplant Research Maquet Otsuka* Novartis None CareDx IMAGE trial (Steering Committee)* NIH* None None Kenneth Casey Organizational Reviewer CHEST Wm. S. Middleton Memorial Veterans Hospital Director, Sleep Medicine None None None None CHEST None M. Fuad Jan Organizational Reviewer CHEST Aurora Advanced Healthcare Cardiologist None None None None None None Kenneth W. Lin Organizational Reviewer AAFP Georgetown University School of Medicine Clinician Educator Track, Associate Professor None None None None None None Joaquin E. Cigarroa Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines Oregon Health & Science University Clinical Professor of Medicine None None None None ACC/AHA AHA ASA Catheterization and Cardiovascular Intervention NIH Portland Metro Area AHA (President) SCAI Quality Interventional Council None Lee A. Fleisher Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines University of Pennsylvania Health System Robert Dunning Dripps Professor of Anesthesiology and Critical Care; Chair, Department of Anesthesiology & Critical Care Blue Cross/ Blue Shield* NQF Yale University None None Johns Hopkins (DSMB) Association of University Anesthesiologists NIH None Samuel S. Gidding Content Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Nemours/Alfred I. duPont Hospital for Children Chief, Division of Pediatric Cardiology FH Foundation International FH Foundation None None FH Foundation NIH* None None James L. Januzzi Content Reviewer Massachusetts General Hospital Hutter Family Professor of Medicine in the Field of Cardiology Critical Diagnostics* Novartis* Phillips Roche Diagnostics* Sphingotec* None None Amgen (DSMB) Boeringer Ingelheim (DSMB)* Janssen Pharmaceuticals (DSMB) Prevencio* None None (Continued) Appendix 2.


S. Middleton Memorial Veterans Hospital Director, Sleep Medicine None None None None CHEST None M. Fuad Jan Organizational Reviewer CHEST Aurora Advanced Healthcare Cardiologist None None None None None None Kenneth W. Lin Organizational Reviewer AAFP Georgetown University School of Medicine Clinician Educator Track, Associate Professor None None None None None None Joaquin E. Cigarroa Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines Oregon Health & Science University Clinical Professor of Medicine None None None None ACC/AHA AHA ASA Catheterization and Cardiovascular Intervention NIH Portland Metro Area AHA (President) SCAI Quality Interventional Council None Lee A. Fleisher Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines University of Pennsylvania Health System Robert Dunning Dripps Professor of Anesthesiology and Critical Care; Chair, Department of Anesthesiology & Critical Care Blue Cross/ Blue Shield* NQF Yale University None None Johns Hopkins (DSMB) Association of University Anesthesiologists NIH None Samuel S. Gidding Content Reviewer ACC/AHA Task Force on Clinical Practice Guidelines Nemours/Alfred I. duPont Hospital for Children Chief, Division of Pediatric Cardiology FH Foundation International FH Foundation None None FH Foundation NIH* None None James L. Januzzi Content Reviewer Massachusetts General Hospital Hutter Family Professor of Medicine in the Field of Cardiology Critical Diagnostics* Novartis* Phillips Roche Diagnostics* Sphingotec* None None Amgen (DSMB) Boeringer Ingelheim (DSMB)* Janssen Pharmaceuticals (DSMB) Prevencio* None None (Continued) Appendix 2. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness CLINICAL STATEMENTS AND GUIDELINES Heart Failure Focused Update on Pharmacological Therapy Jos A. Joglar Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines UT Southwestern Medical Center Professor of Internal Medicine; Clinical Cardiac Electrophysiology Program Director None None None None None None Edward K. Kasper Content Reviewer Johns Hopkins Cardiology E. Cowles Andrus Professor in Cardiology None None None None None None Wayne C. Levy Content Reviewer University of Washington Professor of Medicine Abbott Laboratories Biotronik GE Healthcare HeartWare PharminIN None None NIH Novartis* St. Jude Medical* Amgen* AHA HeartWare* Novartis* Resmed* Thoratec None Judith E. Mitchell Content Reviewer SUNY Downstate Medical Center Director/Heart Failure Center; SUNY Downstate College of Medicine Associate Professor of Medicine None None None None Association of Black Cardiologists None Sean P. Pinney Content Reviewer ACC Heart Failure and Transplant Council Mount Sinai School of Medicine Associate Professor of Medicine, Cardiology Acorda Therapeutics Thoratec CareDX None None Thoratec NIH None None Randall C. Starling Content Reviewer ACC Heart Failure and Transplant Council Cleveland Clinic Department of Cardiovascular Medicine Vice Chairman,Department of Cardiovascular Medicine; Section Head,Heart Failure & CardiacTransplant BioControl Medtronic Novartis None None Medtronic NIH* Novartis St. Jude Medical St. Jude Medical None W. H. Wilson Tang Content Reviewer Cleveland Clinic Foundation Assistant Professor of Medicine None None None NIH* Alnylam Pharmaceuticals NIH NHLBI Roche Novartis Thoratec None Emily J. Tsai Content Reviewer Columbia University College of Physicians & Surgeons Assistant Professor, Section of Cardiology None None None Bayer Bristol-Myers Squib NHLBI* None None Duminda N. Wijeysundera Content Reviewer ACC/ AHA Task Force on Clinical Practice Guidelines Li Ka Shing Knowledge Institute of St. Michael s Hospital Scientist; University of Toronto Assistant Professor, Department of Anesthesia and Institute of Health Policy Management and Evaluation None None None CIHR (DSMB) CIHR* Heart and Stroke Foundation of Canada* Ministry of Health & Long-term Care of Ontario* PCORI (DSMB) 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.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.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. American College of Physicians did not provide a peer reviewer for this document. *Significant relationship. No financial benefit. AAFP indicates American Academy of Family Physicians; ACC,American College of Cardiology; AHA,American Heart Association; ASA,American Stroke Association; CHEST,American College of Chest Physicians; CIHR, Canadian Institutes of Health Research; DSMB, data safety monitoring board; FH, familial hypercholesterolemia; GWTG, Get With The Guidelines; HFSA, Heart Failure Society of America; IMAGE, Invasive Monitoring Attenuation through Gene Expression; ISHLT, International Society for Heart and Lung Transplantation; NIH, National Institutes of Health; NHLBI, National Heart, Lung, and Blood Institute; NQF, National Quality Forum; PCORI, Patient-Centered Outcomes Research Institute; SCAI, Society for Cardiovascular Angiography and Interventions; SUNY, State University of New York; UT, University of Texas; and VA, Veterans Affairs. Appendix 2. Continued Reviewer Representation Employment Consultant Speakers Bureau Ownership/ Partnership/ Principal Personal Research Institutional, Organizational, or Other Financial Benefit Expert Witness


ACC/AHA TASK FORCE ON PERFORMANCE MEASURES Gregg C. Fonarow, MD, FACC, FAHA, Chair; Paul A. Heidenreich, MD, MS, FACC, FAHA, Immediate Past Chair; Nancy M. Albert, PhD, CCNS, CCRN, FAHA ; Geoffrey D. Barnes, MD, MSc, FACC ; Paul S. Chan, MD, MSc, FACC ; Lesley H. Curtis, PhD ; Lauren Gilstrap, MD ; Michelle Gurvitz, MD, FACC ; P. Michael Ho, MD, PhD, FACC, FAHA ; Corrine Y. Jurgens, PhD, RN, ANP-BC, FAHA ; Sean O Brien, PhD ; Jeffrey Olin, DO, FACC, FAHA ; Tiffany Randolph, MD ; Andrea M. Russo, MD, FACC ; Randal J. Thomas, MD, FACC, FAHA ; Paul D. Varosy, MD, FACC ; Robert Yeh, MD, FACC ; Samad Zaheeruddin, MD 2017 by the American Heart Association, Inc., and the American College of Cardiology Foundation. Circ Cardiovasc Qual Outcomes is available at http://circoutcomes.ahajournals.org DOI: 10.1161/HCQ.0000000000000032 *ACC/AHA Task Force on Performance Measures Liaison. Society for Cardiovascular Angiography and Interventions Representative. American College of Cardiology Representative. American Heart Association Representative. The American Heart Association and the American College of Cardiology make every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This document was approved by the American College of Cardiology Clinical Policy Approval Committee on May 22, 2017, the American Heart Association Science Advisory and Coordinating Committee on June 7, 2017, the American Heart Association Executive Committee on August 11, 2017, and the Society for Cardiovascular Angiography and Interventions on July 17, 2017.


This document was approved by the American College of Cardiology Clinical Policy Approval Committee on May 22, 2017, the American Heart Association Science Advisory and Coordinating Committee on June 7, 2017, the American Heart Association Executive Committee on August 11, 2017, and the Society for Cardiovascular Angiography and Interventions on July 17, 2017. The Comprehensive RWI Data Supplement table is available with this article at http://circoutcomes.ahajournals.org/lookup/suppl/doi:10.1161/ HCQ.0000000000000032/-/DC1. The American Heart Association requests that this document be cited as follows: Jneid H, Addison D, Bhatt DL, Fonarow GC, Gokak S, Grady KL, Green LA, Heidenreich PA, Ho PM, Jurgens CY, King ML, Kumbhani DJ, Pancholy S. 2017 AHA/ACC clinical performance and quality measures for adults with ST-elevation and non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. Circ Cardiovasc Qual Outcomes. 2017;10:e000032. doi: 10.1161/HCQ.0000000000000032. This article has been copublished in the Journal of the American College of Cardiology. Copies: This document is available on the World Wide Web sites of the American College of Cardiology (www.acc.org) and the American Heart Association (professional.heart.org). A copy of the document is available at http://professional.heart.org/statements by selecting either the By Topic link or the By Publication Date link. 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 and select the Policies and Development link. 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. (Circ Cardiovasc Qual Outcomes. 2017;10:e000032. DOI: 10.1161/HCQ.0000000000000032.)


A link to the Copyright Permissions Request Form appears on the right side of the page. (Circ Cardiovasc Qual Outcomes. 2017;10:e000032. DOI: 10.1161/HCQ.0000000000000032.) 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures Developed in Collaboration With the Society for Cardiovascular Angiography and Interventions Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation WRITING COMMITTEE MEMBERS Hani Jneid, MD, FACC, FAHA, Chair; Daniel Addison, MD; Deepak L. Bhatt, MD, MPH, FACC, FAHA; Gregg C. Fonarow, MD, FACC, FAHA; Sana Gokak, MPH; Kathleen L. Grady, PhD, FAHA; Lee A.


2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction A Report of the American College of Cardiology/American Heart Association Task Force on Performance Measures Developed in Collaboration With the Society for Cardiovascular Angiography and Interventions Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation WRITING COMMITTEE MEMBERS Hani Jneid, MD, FACC, FAHA, Chair; Daniel Addison, MD; Deepak L. Bhatt, MD, MPH, FACC, FAHA; Gregg C. Fonarow, MD, FACC, FAHA; Sana Gokak, MPH; Kathleen L. Grady, PhD, FAHA; Lee A. Green, MD, MPH; Paul A. Heidenreich, MD, MS, FACC, FAHA*; P. Michael Ho, MD, PhD, FACC, FAHA; Corrine Y. Jurgens, PhD, RN, ANP-BC, FAHA; Marjorie L. King, MD, FACC; Dharam J. Kumbhani, MD, SM, FACC, FAHA; Samir Pancholy, MD, FACC AHA/ACC Performance Measures 2 Table of Contents Scope of the Problem 3 Disclosure of Relationships With Industry and Other Entities 4 Definition and Selection of Measures 5 AHA/ACC STEMI and NSTEMI Measure Set Performance Measures 6 Discussion of Changes to 2008 STEMI and NSTEMI Measure Set 6 Areas for Further Research 9 Appendix A STEMI and NSTEMI Performance Measures 15 Performance Measures for Use in Patients With Inpatient STEMI and NSTEMI 15 Inpatient Measures 15 Short Title: PM-1: Aspirin at Arrival 15 Short Title: Short Title: PM-3: Beta Blocker at Short Title: PM-4: High-Intensity Statin Short Title: Short Title: Short Title: Short Title: PM-8: First Medical Short Title: Short Title: PM-10: Door-in-Door-Out Time 22 Short Title: PM-11: Time to Primary PCI Among Transferred Patients 24 Short Title: PM-12: Cardiac Rehabilitation Short Title: Inhibitor at Short Title: PM-14: ImmediateAngiography After Cardiac Arrest 26 Short Title: PM-15: Stress Test in Conservatively Treated Patients 27 Short Title: PM-16: Early Troponin Measurement After NSTEMI 28 Short Title: PM-17: AMI Registry Quality Improvement Measures for Inpatient STEMI and NSTEMI Patients 29 Inpatient Measures 29 Short Title: QM-1: Risk Score Stratification Short Title: QM-2: Early Invasive Strategy for High-Risk NSTEMI 30 Short Title: Hypothermia for STEMI Patients 31 Short Title: QM-4: Aldosterone Antagonist Short Title: QM-5: Inappropriate In-Hospital Use of NSAIDs 32 Short Title: Prasugrel at Discharge in Short Title: High-Dose Aspirin With Ticagrelor at Discharge 34 Appendix B Author Listing of Relationships With Industry and Other Entities (Relevant) 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction 35 Appendix C Peer Reviewer Relationships With Industry and Other Entities 2017 AHA/ACC Clinical Performance and Quality Measures for Adults With ST-Elevation and Non ST-Elevation Myocardial Infarction 37 Preamble The American College of Cardiology (ACC)/American Heart Association (AHA) performance measure sets serve as vehi- cles to accelerate translation of scientific evidence into clini- cal practice.


Measure sets developed by the ACC/AHA are intended to provide practitioners and institutions that deliver cardiovascular services with tools to measure the quality of care provided and identify opportunities for improvement. Writing committees are instructed to consider the meth- odology of performance measure development1 and to ensure that the measures developed are aligned with ACC/AHA clinical practice guidelines. The writing committees also are charged with constructing measures that maximally cap- ture important aspects of care quality, including timeliness, safety, effectiveness, efficiency, equity, and patient-centered- ness, while minimizing, when possible, the reporting burden imposed on hospitals, practices, and/or practitioners. Potential challenges from measure implementation may lead to unintended consequences. The manner in which chal- lenges are addressed is dependent on several factors, includ- ing the measure design, data collection method, performance attribution, baseline performance rates, reporting methods, and incentives linked to these reports. The ACC/AHA Task Force on Performance Measures (Task Force) distinguishes quality measures from performance measures. Quality measures are those metrics that may be use- ful for local quality improvement but are not yet appropriate for public reporting or pay for performance programs (uses of performance measures). New measures are initially evalu- ated for potential inclusion as performance measures. In some cases, a measure is insufficiently supported by the guidelines. In other instances, when the guidelines support a measure, the writing committee may feel it is necessary to have the measure tested to identify the consequences of measure implementation. Quality measures may then be promoted to the status of per- formance measures as supporting evidence becomes available.


Quality measures may then be promoted to the status of per- formance measures as supporting evidence becomes available. Gregg C. Fonarow, MD, FACC, FAHA Chair, ACC/AHA Task Force on Performance Measures 3 In the summer of 2015, the Task Force convened the writing committee to begin the process of revising the existing set of performance measures for adult patients hospitalized with ST-Elevation and Non ST-Elevation Myocardial Infarction (STEMI and NSTEMI, respectively), that was last updated in The writing committee was charged with the task of developing new measures to benchmark and improve the qual- ity of care for patients with STEMI and NSTEMI. All the measures included in the measure set are briefly summarized in Table 1, which provides information on the measure number, title, care setting, attribution, and domain. The detailed measure specifications (available in Appendix A) provide not only the information included in Table 1, but also more detailed information including the measure description, numerator, denominator (including denominator exclusions and exceptions), rationale for the measure, guideline recom- mendations that support the measure, measurement period, and sources of data. The writing committee has developed a comprehensive STEMI/NSTEMI measure set that includes 24 total measures of which 17 are performance measures and 7 are quality mea- sures (as reflected in Table 1 and Appendix A). The writing committee believes that implementation of this measure set by healthcare providers, physician practices, and hospital sys- tems will enhance the quality of care and likely improve out- comes of patients with STEMI and NSTEMI. 1.1. Scope of the Problem Acute myocardial infarction (AMI) is a frequent cause of hospital admission in the United States and is associated with significant short- and long-term mortality and mor- bidity.


Scope of the Problem Acute myocardial infarction (AMI) is a frequent cause of hospital admission in the United States and is associated with significant short- and long-term mortality and mor- bidity. Every 42 seconds, approximately 1 American will suffer an AMI, and the estimated annual incidences of new and recurrent MI events are 550 000 and 200 000 events, Fortunately, the rates of hospitalization and 30-day mor- tality for AMI have been on the decline.4,5 This reduction in mortality is likely related to the shift in the pattern of clinical presentation of AMI as well as to improved acute treatments and long-term care. Yeh and colleagues examined age- and sex-adjusted incidence rates for STEMI and NSTEMI from a community-based population (Northern California) between 1999 and 2008, and demonstrated an overall significant decrease in AMI incidence rate after 2000.6 Although the adjusted 30-day mortality rate after AMI decreased signifi- cantly (driven by a significant reduction in NSTEMI mortal- ity), the overall mortality rate in 2008 after an AMI was still Importantly, AMI patients who survive the initial event have substantial risk for future cardiovascular events, includ- ing recurrent MI, death, heart failure, and stroke.


Yeh and colleagues examined age- and sex-adjusted incidence rates for STEMI and NSTEMI from a community-based population (Northern California) between 1999 and 2008, and demonstrated an overall significant decrease in AMI incidence rate after 2000.6 Although the adjusted 30-day mortality rate after AMI decreased signifi- cantly (driven by a significant reduction in NSTEMI mortal- ity), the overall mortality rate in 2008 after an AMI was still Importantly, AMI patients who survive the initial event have substantial risk for future cardiovascular events, includ- ing recurrent MI, death, heart failure, and stroke. In the PLATO (Platelet Inhibition and Patient Outcomes) trial, the rate of the combined cardiovascular endpoint (vascular death, MI, or stroke) was 11.7% at 12 months among AMI patients treated with aspirin and clopidogrel.7 This included a 6.9% rate of recurrent MI at 12 months.7 In 2010 alone, about 595000 inpatient hospital discharges were attributed to AMI.3 AMI is also associated with a substantial direct and indirect cost burden, and is classified among the top 10 most expensive hospital principal discharge diagnoses.3 As indicated in the Third Universal Definition of Myocardial Infarction consensus document published in AMI is defined by the detection of a rise and/or fall of cardiac biomarkers (preferably cardiac troponin levels) with at least 1 value above the 99th percentile upper reference limit and with at least one of the following: (a) symptoms of ischemia; (b) new or presumed new signi cant ST-segment T wave changes or new left bundle branch block; (c) develop- ment of pathological Q waves in the electrocardiogram (ECG); (d) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; (e) identi cation of an intracoronary thrombus by angiography or autopsy.


In the PLATO (Platelet Inhibition and Patient Outcomes) trial, the rate of the combined cardiovascular endpoint (vascular death, MI, or stroke) was 11.7% at 12 months among AMI patients treated with aspirin and clopidogrel.7 This included a 6.9% rate of recurrent MI at 12 months.7 In 2010 alone, about 595000 inpatient hospital discharges were attributed to AMI.3 AMI is also associated with a substantial direct and indirect cost burden, and is classified among the top 10 most expensive hospital principal discharge diagnoses.3 As indicated in the Third Universal Definition of Myocardial Infarction consensus document published in AMI is defined by the detection of a rise and/or fall of cardiac biomarkers (preferably cardiac troponin levels) with at least 1 value above the 99th percentile upper reference limit and with at least one of the following: (a) symptoms of ischemia; (b) new or presumed new signi cant ST-segment T wave changes or new left bundle branch block; (c) develop- ment of pathological Q waves in the electrocardiogram (ECG); (d) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality; (e) identi cation of an intracoronary thrombus by angiography or autopsy. The Third Universal Definition of Myocardial Infarction consen- sus document, published in 2012, classifies MI into 5 types, based on pathological, clinical, and prognostic differences, along with different treatment strategies.8 The performance and quality measures described in the current document are predominantly pertinent to patients with spontaneous MI, or MI type 1. MI type 1 is an event related to atherosclerotic plaque disruption (eg, rupture, ulceration, erosion) with super- imposed thrombus formation in a coronary artery, resulting in acute reduction in myocardial blood supply and/or distal embolization with subsequent myonecrosis.