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Evaluating the Application of Chronic Heart Failure Therapies and Developing Treatments in Individuals With Recent Myocardial InfarctionA Review

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Importance  Despite advances in cardiac care, patients remain at a high risk of death and the development of heart failure (HF) following myocardial infarction (MI). These risks are highest in patients with reduced ejection fraction (EF) or signs of HF immediately after MI. Drugs to mitigate these risks have been identified through the systematic evaluation of therapies with proven efficacy in patients with HF and reduced EF (HFrEF).

Observations  Although landmark studies in patients with HFrEF consistently exclude patients with recent MI, dedicated post-MI trials of these drugs have led to multiple therapies with proven benefit in these patients. However, not all therapies with proven efficacy in patients with chronic HF have been shown to provide benefit in the post-MI population, as recently evidenced by the discrepant results between chronic HF and post-MI trials of sacubitril-valsartan. Similarly, multiple trials of early and aggressive use of therapies effective in chronic heart failure immediately post-MI failed to demonstrate benefit or were associated with harm, emphasizing the vulnerability of the post-MI population.

Conclusions and Relevance  Trials of patients at high risk of HF following MI have emphasized the differences between the post-MI and HFrEF populations and the necessity for dedicated trials in the post-MI population. This review summarizes trials studying the use of these therapies for at-risk patients following MI from therapies used in patients with HFrEF and exploring new potential therapies for this high-risk population.

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Article Information

Accepted for Publication: July 13, 2022.

Published Online: August 31, 2022. doi:10.1001/jamacardio.2022.2847

Correction: This article was corrected on October 12, 2022, to fix the presentation of the author name W. Schuyler Jones.

Corresponding Author: Javed Butler, MD, MPH, MBA, Baylor Scott and White Research Institute, 3434 Live Oak St, Ste 501, Dallas, TX 75204 (javed.butler@bwshealth.org).

Author Contributions: Drs Harrington and Butler had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Harrington, Petrie, Bhatt, Jones, Hernandez, Butler.

Acquisition, analysis, or interpretation of data: Harrington, Anker, Bhatt, Jones, Udell, Butler.

Drafting of the manuscript: Harrington, Petrie, Butler.

Critical revision of the manuscript for important intellectual content: Harrington, Anker, Bhatt, Jones, Udell, Hernandez, Butler.

Administrative, technical, or material support: Hernandez.

Supervision: Petrie, Jones, Butler.

Conflict of Interest Disclosures: Dr Harrington reported salary support from T32 training grant T32HL069749. Dr Petrie reported grants from AstraZeneca, Boehringer Ingelheim, Novartis, Novo Nordisk, Vifor, and SQ Innovations; personal fees from AstraZeneca, Boehringer Ingelheim, Novartis, Novo Nordisk, Pharmacosmos, Bayer, Takeda, and SQ Innovations outside the submitted work; is supported by the British Heart Foundation Centre of Research Excellence Award; receives research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, and Pharmacosmos; and serves as a consultant and on end point committees for Boehringer Ingelheim, Novartis, AstraZeneca, Novo Nordisk, AbbVie, Bayer, Takeda, Cardiorentis, and Pharmacosmos. Dr Anker reported receiving fees from Abbott, Bayer, Boehringer Ingelheim, Cardiac Dimension, Impulse Dynamics, Novartis, Occlutech, Servier, and Vifor Pharma and grant support from Abbott and Vifor Pharma. Dr. Bhatt discloses the following relationships: serving on the advisory board for AngioWave, Bayer, Boehringer Ingelheim, Cardax, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Regado Biosciences, Stasys; serving on the board of directors for AngioWave (stock options), Boston Veterans Affairs Research Institute, Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock), Society of Cardiovascular Patient Care, TobeSoft; serving as chair for the American Heart Association Quality Oversight Committee (inaugural chair); serving as a consultant for Broadview Ventures; serving on the data monitoring committees for Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (chair, PEITHO trial), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Contego Medical (chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical), Novartis, Population Health Research Institute, Rutgers University (for the National Institutes of Health–funded MINT trial); receiving honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org; chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (editor in chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (editor in chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor; associate editor), K2P (cochair, interdisciplinary curriculum), Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (course director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national coleader, funded by Bayer), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), WebMD (CME steering committees), Wiley (steering committee); serving as deputy editor for Clinical Cardiology, chair for the NCDR-ACTION Registry Steering Committee, chair for the VA CART Research and Publications Committee; holding patents for sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither Dr Bhatt nor Brigham and Women’s Hospital receive any income from this patent); receiving research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, 89Bio; receiving royalties from Elsevier (editor, Braunwald’s Heart Disease); serving as site coinvestigator for Abbott, Biotronik, Boston Scientific, Cardiovascular Systems Incorporated, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions; serving as trustee for American College of Cardiology; and conducting unfunded research for FlowCo, Takeda. Dr Udell reported speaker/consulting honoraria from Amgen, Boehringer Ingelheim, Janssen, Merck, Novartis, and Sanofi; grant support to his institutions from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Novartis, and Sanofi; personal fees from AstraZeneca and GlaxoSmithKline outside the submitted work. Dr Hernandez reported research grants from American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Merck, Novartis, and Verily and consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Myokardia, Novo Nordisk. Dr Jones reported research grants from Agency for Healthcare Research and Quality, Amgen, Bayer, Boehringer Ingelheim, American Regent, Doris Duke Charitable Foundation, Merck National Institutes of Health, Patient-Centered Outcomes Research Institute, Verily; honoraria or other support from Bayer, Bristol Myers Squibb, and Janssen Pharmaceuticals; and personal fees from AstraZeneca, Boston Scientific, Cytokinetics, and Bristol Myers Squibb outside the submitted work. Dr Butler reports serving as a consultant to Abbott, Adrenomed, Amgen, Array, AstraZeneca, Bayer, Berlin Cures, Boehringer Ingelheim, Bristol Myers b, CVRx, G3 Pharmaceutical, Innolife, Janssen, LivaNova, Luitpold, Medtronic, Merck, Novartis, Novo Nordisk, Occlutech, Relypsa, Roche, Sanofi, SC Pharma, V-Wave Limited, and Vifor. No other disclosures were reported.

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Cherney  DZI , Udell  JA .  Use of sodium glucose cotransporter 2 inhibitors in the hands of cardiologists: with great power comes great responsibility.   Circulation. 2016;134(24):1915-1917. doi:10.1161/CIRCULATIONAHA.116.024764PubMedGoogle ScholarCrossref
Anker  SD , Butler  J , Filippatos  GS ,  et al; EMPEROR-Preserved Trial Committees and Investigators.  Evaluation of the effects of sodium-glucose co-transporter 2 inhibition with empagliflozin on morbidity and mortality in patients with chronic heart failure and a preserved ejection fraction: rationale for and design of the EMPEROR-Preserved Trial.   Eur J Heart Fail. 2019;21(10):1279-1287. doi:10.1002/ejhf.1596PubMedGoogle ScholarCrossref
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AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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