2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction PDF

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 83, NO. 15, 2024 ª 2024 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY...

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY VOL. 83, NO. 15, 2024 ª 2024 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER EXPERT CONSENSUS DECISION PATHWAY 2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction A Report of the American College of Cardiology Solution Set Oversight Committee Writing Thomas M. Maddox, MD, MSC, FACC, Chair Nasrien E. Ibrahim, MD, MPH, FACC Committee James L. Januzzi JR, MD, FACC, Vice Chair JoAnn Lindenfeld, MD, FACC Frederick A. Masoudi, MD, MSPH, MACC Larry A. Allen, MD, MHS, FACC Shweta R. Motiwala, MD, MPH, FACC Khadijah Breathett, MD, MS, FACC Estefania Oliveros, MD, MSC, FACC Sara Brouse, PHARMD, BCCP, BCPS, FACC Mary Norine Walsh, MD, MACC Javed Butler, MD, MBA, MPH, FACC Alan Wasserman, MD, FACC Leslie L. Davis, PHD, RN, ANP-BC, FACC Clyde W. Yancy, MD, MSC, MACC Gregg C. Fonarow, MD, FACC Quentin R. Youmans, MD, MSC Solution Set Nicole M. Bhave, MD, FACC, Chair Dharam J. Kumbhani, MD, SM, FACC Oversight Gurusher S. Panjrath, MBBS, FACC Committee Niti R. Aggarwal, MD, FACC Barbara Wiggins, PHARMD, FACC Katie Bates, ARNP, DNP David E. Winchester, MD, MS, FACC Biykem Bozkurt, MD, PHD, FACC Megan Coylewright, MD, MPH, FACC—Ex Officio John P. Erwin III, MD, FACC TABLE OF CONTENTS OVERVIEW....................................... 1445 2.2 Definitions................................... 1446 3. PATHWAY SUMMARY GRAPHIC................... 1447 1. INTRODUCTION................................. 1445 Figure 1. Ten Pivotal Issues About HFrEF........... 1448 2. ASSUMPTIONS AND DEFINITIONS................. 1446 4. DESCRIPTION AND RATIONALE: 2.1. General Clinical Assumptions.................... 1446 ANSWERS TO 10 PIVOTAL ISSUES IN HF........... 1447 This document was approved by the American College of Cardiology Clinical Policy Approval Committee in February 2024. The American College of Cardiology requests that this document be cited as follows: Maddox TM, Januzzi JL Jr, Allen LA, Breathett K, Brouse S, Butler J, Davis LL, Fonarow GC, Ibrahim NE, Lindenfeld J, Masoudi FA, Motiwala SR, Oliveros E, Walsh MN, Wasserman A, Yancy CW, Youmans QR. 2024 ACC expert consensus decision pathway for treatment of heart failure with reduced ejection fraction: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol 2024;83(15):1444-1488. Copies: This document is available on the website of the American College of Cardiology (www.acc.org). For copies of this document, please contact Elsevier Inc. Reprint Department via fax (212-633-3820) or e-mail ([email protected]). Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American College of Cardiology. Requests may be completed online via the Elsevier site (https://www.elsevier.com/about/policies/ copyright/permissions). ISSN 0735-1097/$36.00 https://doi.org/10.1016/j.jacc.2023.12.024 JACC VOL. 83, NO. 15, 2024 Maddox et al 1445 APRIL 16, 2024:1444–1488 ACC Expert Consensus Decision Pathway for Treatment of HFrEF 4.1. How to Initiate, Add, or Switch to Evidence- 5. DISCUSSIONS AND IMPLICATIONS OF PATHWAY..... 1477 Based Guideline-Directed Therapy for HFrEF. 1447 4.1.1. Initiating GDMT.................... 1447 REFERENCES................................. 1478 Figure 2. Treatment Algorithm for Guideline-Directed Medical Therapy...... 1450 APPENDIX 1 Figure 3. GDMT, Including Newer Therapies in the ECDP for Chronic HF............ 1451 Author Relationships With Industry and Other Entities (Relevant)....................... 1485 4.1.2. Angiotensin Receptor/Neprilysin Inhibitor.......................... 1452 APPENDIX 2 4.1.3. Initiation of an ARNI De Novo Without Prior Exposure to an ACE Inhibitor or ARB... 1455 Peer Reviewer Relationships With Industry and 4.1.4. SGLT Inhibitors.................... 1457 Other Entities (Comprehensive)................. 1487 4.1.5. Ivabradine......................... 1458 APPENDIX 3 4.1.6. Vericiguat......................... 1459 4.1.7. Consensus Pathway Algorithm for Initiation Abbreviations................................ 1488 and Titration of HFrEF Therapies...... 1459 4.1.8. Mitral Regurgitation and the Use of OVERVIEW Transcatheter Mitral Valve Repair..... 1459 4.1.9. Patients in Whom New Therapies The 2021 Update to the 2017 American College of Cardi- May Not Be Indicated............... 1460 ology (ACC) Expert Consensus Decision Pathway for 4.2. How to Achieve Optimal Therapy Given Multiple Optimization of Heart Failure Treatment: Answers to 10 Drugs for HF, Including Augmented Clinical Pivotal Issues About Heart Failure With Reduced Ejection Assessment That May Trigger Additional Fraction 1 provided a practical, streamlined resource for Changes in GDMT (eg, Imaging Data, Biomarkers, and Filling Pressures).......... 1460 clinicians managing patients with heart failure with reduced ejection fraction (HFrEF). The expert consensus 4.2.1. Target Doses....................... 1460 decision pathway (ECDP) provided guidance on intro- 4.2.2. Barriers to Medication Titration....... 1461 ducing the numerous evidence-based therapies, 4.2.3. Clinical Assessment................. 1462 improving adherence, overcoming treatment barriers, Figure 4. Testing and Medication Titration acknowledging contraindications and situations for which Following Diagnosis of HFrEF.......... 1463 little data exist, affording expensive therapies, treating 4.2.4. When to Order an Echocardiogram.... 1462 special cohorts, and making the transition to palliative 4.2.5. Biomarkers—When to Order care. Rather than focusing on extensive text, the docu- Natriuretic Peptides................. 1462 ment provided practical tips, tables, and figures to make 4.2.6. Filling Pressure Assessment—When and clear the steps, tools, and provisos needed to treat the How to Measure Filling Pressures..... 1464 patient with HFrEF successfully and expeditiously. Many 4.3. When to Refer to an HF Specialist.......... 1464 of the pivotal issues addressed in the ECDP were not the 4.4. How to Optimize Care Coordination......... 1465 substance of clinical trials; rather, they represent the 4.5. How to Improve Adherence................ 1466 challenge of clinical practice. 4.5.1. Medication Nonadherence............ 1466 Since publication of the 2021 ECDP, new data have 4.5.2. General Approaches to developed that necessitate an update to the ECDP, Improving Adherence............... 1467 including publication of the 2022 AHA/ACC/HFSA Guide- 4.5.3. Systems and Policies to line for the Management of Heart Failure.2 This update Promote Adherence................. 1468 thus serves as updated guidance to clinicians based on contemporary knowledge. The treatment of HFrEF can 4.6. What is Needed in Specific Patient Cohorts: African-American Populations, Older Adults, feel overwhelming, and many opportunities to improve and Patients Living With Frailty............ 1469 patient outcomes are being missed; hopefully, this ECDP will streamline care to realize the best possible patient 4.7. How to Manage Patients’ Costs and Access to HF Medications.......................... 1470 outcomes in HF (heart failure). 4.8. How to Manage the Increasing Complexity of 1. INTRODUCTION HF Management......................... 1472 4.9. How to Manage Common Comorbidities..... 1475 The prevalence of HF is escalating rapidly, with a pro- 4.10. How to Integrate Palliative Care and Transition jected increase of 34% in upcoming decades.3,4 Com- to Hospice Care.......................... 1476 pounding this, HF is a syndrome that consumes 1446 Maddox et al JACC VOL. 83, NO. 15, 2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF APRIL 16, 2024:1444–1488 substantial health care resources, inflicts considerable with left ventricular ejection fractions (LVEFs) higher morbidity and mortality, and adversely affects quality of than 40%, this document focuses primarily on the life. Important breakthroughs have redefined opportu- management of patients with chronic HFrEF with nities to change the natural history of HF with a broad LVEF #40% in the ambulatory setting and without range of medical therapies, devices, and care strategies. symptoms or signs of clinical instability. For a patient The purpose of this document is to update the 2021 presenting with symptoms of orthopnea or uncom- ECDP with further data from recent studies and to provide fortable peripheral edema, the initial therapy would succinct, practical guidance for managing patients with include diuretic agent therapy with early follow-up to HFrEF. The format of the 10 Pivotal Issues in the ensure progress toward decongestion; following that, prior versions of this ECDP was preserved, and their the steps outlined in this document would apply. For associated treatment algorithms and tables have been more information on care of worsening HF/congestion, updated to accommodate the evolving evidence. The the reader is directed to the ACC ECDP on Risk Preface and Methods sections are accessible online in the Assessment, Management, and Clinical Trajectory of Supplemental Appendix. Patients Hospitalized with HF. 6 3. The expert consensus Writing Committee endorses the Ten Pivotal Issues in HFrEF evidence-based approaches to HF therapy and man- 1. How to initiate, add, or switch therapies with agement enumerated in the 2022 AHA/ACC/HFSA HF consideration of newer evidence-based guideline- guideline.2 directed treatments for HFrEF. 4. These algorithms assume the clinician will seek input 2. How to achieve optimal therapy given multiple drugs as needed from a pharmacist, a cardiologist, an HF for HF, including augmented clinical assessment (eg, specialist, and/or a disease management program, and/ imaging data, biomarkers, and filling pressures) that or other relevant specialists (eg, endocrinologists or may trigger modifications in guideline-directed nephrologists) to guide clinical management. therapy. 5. In all cases, patient preferences and values, in addition 3. When to refer to an HF specialist. to evidence-based clinical judgment, should guide 4. How to enhance care coordination. clinical decision-making. 5. How to improve medication adherence. 6. At any point in time, these suggestions and algorithms 6. How to tailor treatment in specific patient cohorts: may be superseded by new data. African-American patients, older adults, and patients with frailty. 2.2. Definitions 7. How to manage patients’ costs and increase access to AHA/ACC/HFSA Stages of HF: HF medications. 8. How to manage the increasing complexity of HF. n Stage A: At risk for HF but without symptoms, struc- 9. How to manage common comorbidities. tural heart disease, or cardiac biomarkers of stretch or 10. How to integrate palliative care and the transition to injury (eg, patients with hypertension, atherosclerotic hospice care. cardiovascular disease, diabetes, metabolic syndrome and obesity, exposure to cardiotoxic agents, genetic variant for cardiomyopathy, or positive family history 2. ASSUMPTIONS AND DEFINITIONS of cardiomyopathy). n Stage B: Structural heart disease but no prior or current To limit inconsistencies in interpretation, specific as- signs or symptoms of HF. Structural heart disease may sumptions (eg, treatment effects in varied populations) include reduced left or right ventricular function, left were considered by the writing group in development of ventricular (LV) hypertrophy, chamber enlargement, the ECDP. References are supplied when applicable or wall motion abnormalities, or valvular heart disease. appropriate. Additionally, evidence for increased filling pressures by invasive hemodynamic measurements or imaging as 2.1. General Clinical Assumptions well as elevated concentrations of B-type natriuretic 1. Although many topics are generalizable to all patients peptide (BNP)/N-terminal pro–B-type natriuretic pep- with HF, the focus of this effort is on patients with tide (NT-proBNP) or high-sensitivity cardiac troponins. HFrEF. The reader is directed to the 2023 ACC ECDP on n Stage C: Structural heart disease with prior or current Management of HFpEF for more focused details on symptoms of HF. care for this population. 5 n Stage D: Marked HF symptoms that interfere with daily 2. Although some of the recommendations may be rele- life, with recurrent hospitalizations despite attempts to vant to patients hospitalized with acute HF or in those optimize GDMT. JACC VOL. 83, NO. 15, 2024 Maddox et al 1447 APRIL 16, 2024:1444–1488 ACC Expert Consensus Decision Pathway for Treatment of HFrEF GDMT: Guideline-directed medical therapy, repre- of the “4 pillars” of GDMT to maximize the early benefits senting treatment options supported for use by clinical of improvement in patient-reported outcomes, reduction practice guidelines. in HF hospitalizations, reduction in mortality, and HFrEF: Clinical HF and LVEF #40%. improved adherence to GDMT.8-14 When using the thera- New York Heart Association (NYHA) functional peutic standard of a 4-drug regimen (ARNI, beta-blocker, classification: mineralocorticoid antagonist, SGLT inhibitor), there is an aggregate treatment effect that includes increasing years n Class I: No limitation of physical activity. Ordinary of survival and years free from cardiovascular (CV) death physical activity does not cause symptoms of HF. or HF hospitalizations. 15 As an example, 4-class medica- n Class II: Slight limitation of physical activity. Comfort- tion initiation reduced the hazard of CV death or hospital able at rest, but ordinary physical activity results in admission for HF significantly (HR: 0.38; 95% CI: 0.3-0.47) symptoms of HF. compared with therapy with just an ACE inhibitor/ARB n Class III: Marked limitation of physical activity. plus a beta-blocker.15-18 Comfortable at rest, but less than ordinary activity Another important development since the publication causes symptoms of HF. of the 2021 ECDP is the growing recognition of the safety n Class IV: Unable to perform any physical activity and urgency of initiating therapies rapidly. As an without symptoms of HF, or symptoms of HF at rest. example, the STRONG-HF (Safety, Tolerability, and Effi- Optimal therapy: GDMT provided at either the target or cacy of Rapid Optimization, Helped by NT-proBNP the highest-tolerated dose for a given patient. Testing, of Heart Failure Therapies) trial showed that Target doses: Doses targeted in clinical trials. among patients admitted to the hospital with acute HF, high-intensity management that included rapid up- 3. PATHWAY SUMMARY GRAPHIC titration of GDMT and close follow-up, with a goal of reaching target doses within 6 weeks of discharge after Figure 1 is an update of the 2017 ACC ECDP Summary hospitalization, was safe, well-tolerated, and associated Graphic outlining the 10 pivotal issues about HFrEF. with a reduced risk of 180-day all-cause death or HF readmission compared with usual care. 18,19 4. DESCRIPTION AND RATIONALE: ANSWERS Finally, the VICTORIA (Vericiguat Global Study in Pa- TO 10 PIVOTAL ISSUES IN HF tients With Heart Failure and Reduced Ejection Fraction) trial showed that in higher-risk patients with HFrEF 4.1. How to Initiate, Add, or Switch to Evidence-Based already on GDMT with worsening symptoms, the oral Guideline-Directed Therapy for HFrEF soluble guanylyl cyclase stimulator vericiguat was supe- Although loop diuretic agents are an important part of the rior to placebo in reducing the risk of HF hospitalization treatment of congestion in the individual with HFrEF, and/or CV death.20 Subsequently, vericiguat was given a once approaching or achieving euvolemia, it is critical to Class 2b recommendation in the updated 2022 AHA/ACC/ add and optimize therapies proven to reduce morbidity HFSA HF guideline.2 In light of these developments, an and mortality. Established pharmacological therapies for update on when and how to add, switch, and titrate all chronic HFrEF include renin-angiotensin inhibitors such HFrEF therapies to maximally tolerated and, ideally, as angiotensin II receptor/neprilysin inhibitors (ARNIs), target doses (Figure 1, Table 1) was deemed important. angiotensin-converting enzyme (ACE) inhibitors, and HF is a complex clinical syndrome typically associated angiotensin receptor blockers (ARBs), along with with multiple comorbidities; most patients are on multi- evidence-based beta-blockers, sodium-glucose cotrans- ple medications. No clinical trials have specifically eval- porter (SGLT) inhibitors, mineralocorticoid antagonists, uated the potential for greater benefit or excessive risk of loop diuretic agents, hydralazine/isosorbide dinitrate indicated therapies among patients with multimorbidity. (HYD/ISDN), ivabradine, and vericiguat. With the excep- To assess tolerability of medications and best assess the tion of loop diuretic agents, all of these therapies have trajectory of HF, it is often necessary for patients to have been shown in randomized controlled trials to improve more frequent follow-ups, especially after initiation or symptoms, reduce hospitalizations, and/or prolong sur- titration of therapy. These follow-ups may be in-person or vival. 2,7 In contrast, use of digoxin as a treatment for virtual on a case-by-case basis and depending on patient HFrEF lacks contemporary data; most of its use in modern stability and adjustment(s) made. HFrEF management focuses on its role as a rate control agent for atrial fibrillation (AF) in those with low blood 4.1.1. Initiating GDMT pressure. Recommendations for starting GDMT in a patient with a Since the publication of the 2021 ECDP, more data have new diagnosis of symptomatic HFrEF are detailed in emerged to support early and rapid initiation and titration Figure 2. 1448 Maddox et al JACC VOL. 83, NO. 15, 2024 ACC Expert Consensus Decision Pathway for Treatment of HFrEF APRIL 16, 2024:1444–1488 F I G U R E 1 Ten Pivotal Issues About HFrEF CV ¼ cardiovascular; GDMT, guideline-directed medical treatment; HF ¼ heart failure; HFrEF ¼ heart failure with reduced ejection fraction. In a patient with new-onset Stage C HFrEF, a com- and titration of GDMT should be early and as rapid as mon question is which medication class to initiate first, possible with a goal to use the 4 key medication classes and a common second question is how rapidly to add in each patient. additional agents and titrate medication doses. There is For the person with de novo HFrEF, therapies should no optimal order of initiation and/or titration, so the be initiated with a goal of reaching target or maximally Writing Committee recommends that clinicians will tolerated doses of the 4 key medication classes as soon need to approach each patient in an individual as possible, and ideally no longer than 3 months. In fashion to decide on which agents to titrate and when many individuals, some GDMT may already be in place, to do so. The Writing Committee also recommends that and the Writing Committee recommends initiation and regardless of the sequencing of agents, careful initiation titration of missing key therapies as rapidly as possible, JACC VOL. 83, NO. 15, 2024 Maddox et al 1449 APRIL 16, 2024:1444–1488 ACC Expert Consensus Decision Pathway for Treatment of HFrEF Starting and Target Doses of GDMT for HF (Choice and timing of each therapy and who should have them added are TABLE 1 discussed in the text)* Starting Dose Target Dose Beta-blockers Bisoprolol 1.25 mg once daily 10 mg once daily Carvedilol 3.125 mg twice daily 25 mg twice daily for weight