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  • Review Article
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Invasive and medical management approaches to non-acute myocardial ischaemic syndromes

Nature Reviews Cardiology (2026)Cite this article

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Abstract

Over the past two decades, approaches to managing patients with coronary artery disease have improved substantially with advances in percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) surgery, pharmacological secondary prevention, anti-anginal agents and lifestyle interventions. Accordingly, clinical management choices in non-acute myocardial ischaemic syndromes (NAMIS) remain a timely and important topic. The risks and benefits of an invasive strategy combined with optimal medical therapy (OMT) versus a conservative strategy of OMT alone should be discussed with patients to facilitate shared clinical decision making. The findings from high-quality, randomized, controlled trials in the era of modern OMT form an essential platform for these informed conversations. In totality, the evidence from randomized, controlled trials supports OMT as the first-line therapeutic approach in patients with NAMIS, whereas selected patients at high anatomical risk or those with persistent anginal symptoms despite initial OMT often derive further symptom relief from invasive therapy with PCI. In patients with high-risk NAMIS, including those with multivessel disease and diabetes mellitus, CABG surgery improves survival, whereas the benefit is less clear for PCI. In this Review, we discuss the findings from contemporary trials evaluating outcomes in patients with NAMIS treated invasively or conservatively with OMT alone, and we conclude with proposed management pathways.

Key points

  • The available evidence supports the optimization of medical therapy as the first-line therapeutic approach for most patients with non-acute myocardial ischaemic syndromes.

  • Physicians should carefully consider selected patients who might benefit from invasive therapy with percutaneous coronary intervention or coronary artery bypass graft surgery.

  • Patients with persistent symptoms who are unable to tolerate up-titration of medications might be candidates for early percutaneous coronary intervention to improve symptoms, especially for non-complex coronary artery disease.

  • Selecting appropriate high-risk patients who would benefit from coronary artery bypass graft surgery continues to be supported by the evidence for improved event-free survival.

  • Prospective studies are warranted both to define subsets of patients with non-acute myocardial ischaemic syndromes who might benefit from invasive therapies and to elucidate the mechanisms by which benefit is derived.

  • The totality of trial-based evidence points towards the need for physicians and patients to engage in shared clinical decision making on whether to proceed with invasive management.

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Fig. 1: Timeline of trials in which revascularization was compared with medical therapy in patients with non-acute myocardial ischaemic syndromes.
Fig. 2: Timeline of trials in which CABG surgery was compared with PCI and/or medical therapy in patients with non-acute myocardial ischaemic syndromes.
Fig. 3: Treatment effects of PCI and CABG surgery in coronary artery disease.

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Authors and Affiliations

  1. Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, Boston, MA, USA

    Nicholas Chiu & David P. Faxon

  2. Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Deepak L. Bhatt

  3. Cardiovascular Division, Pisa University Hospital – University of Pisa, Pisa, Italy

    Raffaele De Caterina

  4. Department of Cardiothoracic Surgery, Jena University Hospital, Friedrich Schiller University, Jena, Germany

    Torsten Doenst & Hristo Kirov

  5. Centro Cardiovascular Universitario, Hospital de Clínicas, Universidad de la Republica, Montevideo, Uruguay

    Victor Dayan

  6. Division of Cardiology, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    Sanjay Kaul

  7. British Heart Foundation Centre for Research Excellence, School of Cardiovascular and Metabolic Medicine and Sciences, King’s College, London, UK

    Divaka Perera

  8. Emory Heart and Vascular Center, Emory University School of Medicine, Atlanta, GA, USA

    John D. Puskas

  9. Université Paris-Cité, Assistance Publique – Hopitaux de Paris, INSERM U1148 and FACT (French Alliance of Cardiovascular Trials), Paris, France

    Philippe Gabriel Steg

  10. VA Boston Healthcare System, Boston University School of Medicine, Boston, MA, USA

    William E. Boden

Authors
  1. Nicholas Chiu
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  2. Deepak L. Bhatt
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  3. Raffaele De Caterina
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  4. Torsten Doenst
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  5. Hristo Kirov
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  6. Victor Dayan
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  7. David P. Faxon
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  8. Sanjay Kaul
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  9. Divaka Perera
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  10. John D. Puskas
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  11. Philippe Gabriel Steg
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  12. William E. Boden
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Contributions

N.C. and W.E.B. researched data for the article. All the authors discussed its content. N.C., R.D.C., T.D. and W.E.B. wrote the manuscript. All the authors reviewed/edited the manuscript before submission.

Corresponding author

Correspondence to William E. Boden.

Ethics declarations

Competing interests

D.L.B. discloses the following relationships: membership of Advisory Boards for Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, E-Star Biotech, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, NirvaMed, Novo Nordisk, Stasys, and Tourmaline Bio; membership of Board of Directors for American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); consultant for Broadview Ventures, Corcept Therapeutics, GlaxoSmithKline, Hims, SFJ, Summa Therapeutics, and Youngene; membership of 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, 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; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute, and Rutgers University (for the NIH-funded MINT trial); 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; 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), CSL Behring (AHA lecture), 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), 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 co-leader, funded by Bayer), WebMD (CME steering committees), and Wiley (steering committee); Clinical Cardiology (Deputy Editor); named on a patent for sotagliflozin (assigned to Brigham and Women’s Hospital who assigned to Lexicon; neither I nor Brigham and Women’s Hospital receive any income from this patent); research funding from Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, and 89Bio; royalties from Elsevier (Editor, Braunwald’s Heart Disease); and Cleerly (site co-investigator). P.G.S. discloses the following relationships: research grants from Amarin and Sanofi; membership of clinical trial steering committee, clinical events committee, and data and safety monitoring board for Amarin, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Janssen, Merck, Novartis, Pfizer and Sanofi; consulting or speaking for Amarin, Amgen, BMS, Novo Nordisk, Novartis and Pfizer; Senior Associate Editor of Circulation; and Chief Medical Officer at Bioquantis. The other authors declare no competing interests.

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Nature Reviews Cardiology thanks Antonio Colombo, Michal Tendera and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Chiu, N., Bhatt, D.L., De Caterina, R. et al. Invasive and medical management approaches to non-acute myocardial ischaemic syndromes. Nat Rev Cardiol (2026). https://doi.org/10.1038/s41569-026-01259-x

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