Stable Coronary Artery Disease: History
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Coronary revascularization is one of the most studied treatment modalities in cardiology; however, there is no consensus among experts about its indications in patients with stable coronary artery disease (SCAD). 

  • chronic coronary syndromes
  • revascularization
  • prognosis
  • angina

1. Introduction

A record number of studies have been conducted on myocardial revascularization in stable coronary artery disease (SCAD) [1], but despite this, the choice between a conservative and invasive strategy in a particular patient remains a complex and controversial issue. The current European Society of Cardiology (ESC) Guidelines, containing sections on myocardial revascularization in SCAD (chronic coronary syndromes [CCS], in ESC terminology), published with an interval of one year [2][3], differ significantly. The recently completed large-scale randomized clinical trial (RCT) ISCHEMIA and the ongoing ISCHEMIA-EXTEND trial provide new evidence for treatment selection in SCAD that conflicts with the current guidelines. Moreover, the published results of ISCHEMIA have already become the subject of a new hot discussion arguing their role as the ultimate guide for decision-making [4][5]. Special attention is directed to the value of revascularization in subpopulations of known high risk, such as 3-vessel disease and unprotected left main coronary artery (LMCA) disease patients (the latter not presented in ISCHEMA) [6].

2. Summary of Guidelines on Myocardial Revascularization before ISCHEMIA

The most significant recommendations on which clinical decision-making in practice has been based in the last decade were the European Guidelines on Myocardial Revascularization [2], the ESC Guidelines for the Diagnosis and Management of Chronic Coronary Syndromes [3], and the American Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease [7]. Revascularization is performed to alleviate the ischemic symptoms or to improve the prognosis.
The indications for revascularization available in the listed sources are summarized below (Table 1 and text).
European revascularization Guidelines [2] are very similar. There, the Class I and IIa indications for myocardial revascularization to improve prognosis are high-risk coronary lesions: left main coronary artery (LMCA) disease; proximal stenosis of the left anterior descending artery (LAD); two or three vessel disease in patients with significantly depressed left ventricular ejection fraction (EF) of <35%; stenosis of the last patent coronary artery (all lesions are considered angiographically significant if ≥50% according to the European standard). Also, inducible ischemia of a large area (>10% of the left ventricle [LV] area) during a stress test is an indication for coronary intervention. To improve symptoms, revascularization is recommended in the presence of hemodynamically significant coronary artery stenosis if the patient has limiting angina or the angina equivalent (dyspnea) with an insufficient response to OMT while considering the patient’s preference. Revascularization of stenosis is warranted if it is >90% by angiography or if 50–90%, when (1) ischemia of >10% LV area is induced in this coronary territory at an imaging stress test or (2) measurement of FFR/instantaneous wave-free ratio (iwFR) gives a result of ≤0.80 or ≤0.89, respectively.
However, the ESC Guidelines on CCS [3] state in contrast that an invasive strategy may improve prognosis in any hemodynamically significant lesion. According to this document, revascularization may be considered in a patient who is asymptomatic (i.e., for prognostic purposes) when (1) ischemia is confirmed by a stress test and the area of inducible ischemia is >10% of the LV, or (2) when the stress test is negative or not carried out, in the presence of stenosis of any localization if hemodinamically significant (defined as above); revascularization should also be considered with an EF < 35% as a result of coronary artery disease. Also, revascularization may be indicated to improve symptoms in a patient with angina and confirmed myocardial ischemia.
Although these guidelines have been the basis of clinical decision-making for a long time, they are controversial. Also, statements on the prognostic benefit of coronary artery bypass grafting (CABG) in individuals with high-risk coronary lesions and reduced EF are based on observational data from the 1980s and 1990s, conducted before the era of modern optimal medical therapy (OMT) [8]. The prognostic advantage of percutaneous coronary intervention (PCI) over OMT was, in fact, only shown in the FAME 2 study, where revascularization was performed after confirming the hemodynamic significance of stenosis by measuring the FFR [9]. These data are the basis of the latest version of the European recommendations [3]. Nevertheless, FAME 2 failed to show differences in the “hard” endpoints of cardiac death, acute myocardial infarction (AMI), and confirmed unstable angina. The only parameter in which the invasive strategy showed superiority was acute coronary syndrome, not confirmed by ECG/biomarkers. The explanation for this is the increased alertness of patients in the “conservative” group of the FAME2 study (and their attending physicians) regarding any suspicious symptoms in a situation where the presence of significant stenosis was proven by FFR and revascularization, which in this case ‘should’ be performed, was not performed due to the conditions of the trial [10]. On the other hand, in the extended (5-year) follow-up of the FAME 2 cohort [11], the authors did show the advantage of PCI in terms of less urgent revascularizations and spontaneous AMIs. Obviously, if PCI of significant stenosis really prevents AMI, this conflicts with the existing idea of the predominant development of atherothrombosis at the site of an insignificant “vulnerable” atherosclerotic plaque [12].

This entry is adapted from the peer-reviewed paper 10.3390/life13071497


  1. Authors/Task Force Members; Windecker, S.; Kolh, P.; Alfonso, F.; Collet, J.P.; Cremer, J.; Falk, V.; Filippatos, G.; Hamm, C.; Head, S.J.; et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS)Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur. Heart J. 2014, 35, 2541–2619.
  2. Neumann, F.J.; Sousa-Uva, M.; Ahlsson, A.; Alfonso, F.; Banning, A.P.; Benedetto, U.; Byrne, R.A.; Collet, J.P.; Falk, V.; Head, S.J.; et al. 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur. Heart J. 2019, 40, 87–165.
  3. Knuuti, J.; Wijns, W.; Saraste, A.; Capodanno, D.; Barbato, E.; Funck-Brentano, C.; Prescott, E.; Storey, R.F.; Deaton, C.; Cuisset, T.; et al. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur. Heart J. 2020, 41, 407–477.
  4. Lopez-Sendon, J.; Moreno, R.; Tamargo, J. ISCHEMIA Trial: Key Questions and Answers. Eur. Cardiol. 2021, 16, e34.
  5. Kanoun Schnur, S.S.; Achim, A.; Toth, G.G. Clinical application of results of the ISCHEMIA trial. Trends Cardiovasc. Med. 2023, 33, 125–130.
  6. Kohsaka, S.; Ejiri, K.; Takagi, H.; Watanabe, I.; Gatate, Y.; Fukushima, K.; Nakano, S.; Hirai, T. Diagnostic and Therapeutic Strategies for Stable Coronary Artery Disease Following the ISCHEMIA Trial. JACC Asia 2023, 3, 15–30.
  7. Fihn, S.D.; Gardin, J.M.; Abrams, J.; Berra, K.; Blankenship, J.C.; Dallas, A.P.; Douglas, P.S.; Foody, J.M.; Gerber, T.C.; Hinderliter, A.L.; et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J. Am. Coll. Cardiol. 2012, 60, e44–e164.
  8. Bershteyn, L.L.; Andreeva, A.E.; Katamadze, N.O.; Zbyshevskaya, E.V.; Kuzmina-Krutetskaya, A.M.; Volkov, A.V.; Gumerova, V.E.; Bitakova, F.I.; Sayganov, S.A. ISCHEMIA—The Largest Ever Randomized Study in Stable Coronary Artery Disease. Baseline Characteristics of Enrolled Patients in One Russian Site. Kardiologiia 2017, 57, 12–19.
  9. Stergiopoulos, K.; Boden, W.E.; Hartigan, P.; Möbius-Winkler, S.; Hambrecht, R.; Hueb, W.; Hardison, R.M.; Abbott, J.D.; Brown, D.L. Percutaneous coronary intervention outcomes in patients with stable obstructive coronary artery disease and myocardial ischemia: A collaborative meta-analysis of contemporary randomized clinical trials. JAMA Intern. Med. 2014, 174, 232–240.
  10. Rajkumar, C.A.; Nijjer, S.S.; Cole, G.D.; Al-Lamee, R.; Francis, D.P. ‘Faith Healing’ and ‘Subtraction Anxiety’ in Unblinded Trials of Procedures: Lessons from DEFER and FAME-2 for End Points in the ISCHEMIA Trial. Circ. Cardiovasc. Qual. Outcomes 2018, 11, e004665, Erratum in Circ Cardiovasc. Qual Outcomes 2018, 11, e000038.
  11. Xaplanteris, P.; Fournier, S.; Pijls, N.H.; Fearon, W.F.; Barbato, E.; Tonino, P.A.; Engstrøm, T.; Kääb, S.; Dambrink, J.-H.; Rioufol, G.; et al. Five-Year Outcomes with PCI Guided by Fractional Flow Reserve. N. Engl. J. Med. 2018, 379, 250–259.
  12. Little, W.C. Angiographic assessment of the culprit coronary artery lesion before acute myocardial infarction. Am. J. Cardiol. 1990, 66, 44G–47G.
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