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Review
. 2023 Feb 7;81(5):505-514.
doi: 10.1016/j.jacc.2022.08.814.

Evolving Management Paradigm for Stable Ischemic Heart Disease Patients: JACC Review Topic of the Week

William E Boden  1 , Mario Marzilli  2 , Filippo Crea  3 , G B John Mancini  4 , William S Weintraub  5 , Viviany R Taqueti  6 , Carl J Pepine  7 , Javier Escaned  8 , Rasha Al-Lamee  9 , Luis Henrique W Gowdak  10 , Colin Berry  11 , Juan Carlos Kaski  12 ; Chronic Myocardial Ischemic Syndromes Task Force
Affiliations
Review

Evolving Management Paradigm for Stable Ischemic Heart Disease Patients: JACC Review Topic of the Week

William E Boden et al. J Am Coll Cardiol. .

Abstract

Management of stable coronary artery disease (CAD) has been based on the assumption that flow-limiting atherosclerotic obstructions are the proximate cause of angina and myocardial ischemia in most patients and represent an important target for revascularization. However, the role of revascularization in reducing long-term cardiac events in these patients has been limited mainly to those with left main disease, 3-vessel disease with diabetes, or decreased ejection fraction. Mounting evidence indicates that nonepicardial coronary causes of angina and ischemia, including coronary microvascular dysfunction, vasospastic disorders, and derangements of myocardial metabolism, are more prevalent than flow-limiting stenoses, raising concerns that many important causes other than epicardial CAD are neither considered nor probed diagnostically. There is a need for a more inclusive management paradigm that uncouples the singular association between epicardial CAD and revascularization and better aligns diagnostic approaches that tailor treatment to the underlying mechanisms and precipitants of angina and ischemia in contemporary clinical practice.

Keywords: coronary microvascular dysfunction; epicardial coronary artery disease; myocardial ischemia; percutaneous coronary intervention; revascularization; stable angina.

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Conflict of interest statement

Funding Support and Author Disclosures This publication was supported by an educational grant from Servier, Suresnes Cedex, France. Support in the development of the manuscript was also provided by Liberum IME, London, United Kingdom. Dr Boden receives research grant support from AbbVie, Amarin Pharmaceuticals, Amgen, AstraZeneca, Sanofi, Massachusetts Veterans Epidemiology Research and Information Center, VA New England Healthcare System’s Clinical Trials Network, and the National Heart, Lung, and Blood Institute (NHLBI), where he served as national co-principal investigator for the ISCHEMIA trial; is on the Board of Directors for the Boston VA Research Institute; receives consulting fees from Amarin Pharmaceuticals, Amgen, Janssen Pharmaceuticals, Metuchen Pharmaceuticals, and Servier; is on the VA Cooperative Studies Program data monitoring committee; and has received speaking honoraria from Amarin, Amgen, Janssen Pharmaceuticals, Pfizer, and Servier. Dr Marzilli lectures for Servier, Menarini, Degussa Pharma Group, Baldacci, Abbott, and AstraZeneca. Dr Crea has received personal speaker fees from Amgen, AstraZeneca, Servier, and BMS; and is a member of the advisory board for GlyCardial Diagnostics. Dr Mancini has received grants, advisory board appointments, and honoraria for educational lectures from Amgen, Sanofi, NovoNordisk, Lilly/Boehringer Ingelheim, and HLI Therapeutics; is on the advisory board for Esperion; and receives reports on grants from the National Institutes of Health (NIH) for the COURAGE and ISCHEMIA trials. Dr Weintraub has received research support from Amarin Corporation, NIH, and Centers for Disease Control and Prevention; and has served as a consultant for Amarin Corporation, AstraZeneca, Pfizer, Janssen, SC Pharma, Lexicon, Faraday, and The Medicines Company. Dr Taqueti is supported by NIH grant K23HL135438. Dr Pepine receives research grant support from NIH/NHLBI (R21AG063143, K08 HL130945, K01 HL138172, R01 HL146158, AG065141, R01 HL152162, R21 HL152264, R01 HL132448, UM1 HL087366, UM1 HL087318), NIH/National Center for Advancing Translational Sciences (UL1 TR001427), U.S. Department of Defense (W81XWH-17-2-0030, WARRIOR), Biocardia, Brigham and Women’s Hospital, CSL Behring, Cytori Therapeutics, DCRI, GE Healthcare, Mesoblast, and Pfizer; receives consultant fees/honoraria from Caladrius Biosciences, Slack, and Xylocor; and receives grant support from the Gatorade Foundation through the University of Florida Department of Medicine and from the McJunkin Family Foundation, Plantation, Florida. Dr Escaned has received speaker and advisory board honoraria from Abbott Laboratories and Philips. Dr Al-Lamee has received speaker honoraria from Philips Volcano, Abbott Vascular, and Menarini Pharmaceuticals. Dr Gowdak has received congress-related travel expenses from Servier; has participated in clinical trials sponsored by Servier and Angion Biomedica; has been a speaker for Servier, Boehringer-Lilly, and Abbott; is an advisory board member for Servier; and has prepared written scientific material for Servier and Abbott. Dr Berry is employed by the University of Glasgow, which holds consultancy and research agreements for his work with Abbott Vascular, AstraZeneca, Auxilius Pharma, Boehringer Ingelheim, Causeway Therapeutics, Coroventis, Genentech, GSK, HeartFlow, Menarini, Neovasc, Siemens Healthcare, and Valo Health; and receives research funding from the British Heart Foundation (grant RE/18/6134217), Chief Scientist Office, Engineering and Physical Sciences Research Council (EP/R511705/1, EP/S030875/1), European Union (754946-2), Medical Research Council (MR/S018905/1), and UKRI (MC/PC/20014). Dr Kaski has received speaker honoraria from A. Menarini Farmaceutica lnternazionale, Servier, and Bayer UK. Dr Escaned has reported that he has no relationships relevant to the contents of this paper to disclose.

Figures

FIGURE 1
FIGURE 1. Clinical Assessment of Myocardial Ischemia and CAD
In SCOT-HEART, most patients with suspected stable coronary artery disease (CAD) did not have epicardial coronary obstructions, with the vast majority (~4 in 5) having angina and/or ischemia not due to epicardial stenoses. CCTA = coronary computed tomography angiography; CMD = coronary microvascular dysfunction; CV = cardiovascular; INOCA = ischemia with no obstructive coronary arteries; MI = myocardial infarction; OMT = optimal medical therapy.
FIGURE 2
FIGURE 2. Antianginal Treatment Directed to the Mechanism Responsible for Ischemia
For exertional angina, antianginal drugs that reduce myocardial oxygen consumption (ie, beta-blockers [BBs], nondihydropyridine calcium-channel blockers [CCBs], or ivabradine) are most efficacious, whereas for variable threshold angina or coronary microvascular dysfunction, agents that improve myocardial oxygen utilization (ie, ranolazine or trimetazidine) are suitable treatment options. CCBs are the preferred option for epicardial or microvascular spasm, but nitrates and nicorandil may also be appropriate. BP = blood pressure; CAD = coronary artery disease; DHP = dihydropyridine; HR = heart rate; LAN = long-acting nitrate.
CENTRAL ILLUSTRATION
CENTRAL ILLUSTRATION. Management Algorithm for Obstructive and Nonobstructive Coronary Causes of Angina
A more inclusive management paradigm for stable coronary artery disease (CAD) patients that addresses the many pathogenetic mechanisms responsible for angina and ischemia is necessary to identify diagnostic and therapeutic approaches that would better tailor the appropriate treatment of obstructive and nonobstructive causes of myocardial ischemia to the underlying ischemia precipitants. Such an approach seeks to promote both evidence-based pharmacologic secondary prevention and procedural interventions as complementary and potentially additive treatments to optimize the management of stable angina patients. ACh = acetylcholine; CCTA = coronary computed tomography angiography; CFR = coronary flow reserve; CV = cardiovascular; FFR = fractional flow reserve (a hyperemic pressure ratio);GDMT = guideline-directed medical therapy; iFR = instantaneous free wave ratio; IMR = index of microvascular resistance; LMD = left main disease.
See this image and copyright information in PMC

References

    1. Grines C, Patel A, Zijlstra F, et al. Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: six-month follow up and analysis of individual patient data from randomized trials. Am Heart J. 2003;145:47–57. - PubMed
    1. Kirov H, Caldonazo T, Rahouma M, et al. A systematic review and meta-analysis of percutaneous coronary intervention compared to coronary artery bypass grafting in non–ST-elevation acute coronary syndrome. Sci Rep. 2022;12:5138. - PMC - PubMed
    1. Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356:1503–1516. - PubMed
    1. BARI 2D Study Group, Frye RL, August P, Brooks MM, et al. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. 2009;360:2503–2515. - PMC - PubMed
    1. Ben-Yehuda O, Kazi DS, Bonafede M, et al. Angina and associated healthcare costs following percutaneous coronary intervention: a real-world analysis from a multi-payer database. Catheter Cardiovasc Interv. 2016;88:1017–1024. - PubMed

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