Skip to main content
Log in

Optimal Medical Therapy as First-Line Therapy for Chronic Coronary Syndromes: Lessons from COURAGE, BARI 2D, FAME 2, and ISCHEMIA

  • Invited Review Article
  • Published:
Cardiovascular Drugs and Therapy Aims and scope Submit manuscript

Abstract

The chronic coronary syndromes (CCS) include patients with a classic history of angina pectoris in the presence of either risk factors for or known atherosclerotic coronary artery disease. Randomized, controlled trials conducted in the optimal medical therapy (OMT) era have convincingly demonstrated that adherence to the outdated paradigm focused on treatment of obstructive coronary disease with initial revascularization fails to reduce death or myocardial infarction and inconsistently reduces angina symptoms. Rather, OMT reduces events and improves symptoms and should be considered first-line treatment for patients with CCS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Availability of Data and Material (data transparency)

Not applicable.

Code Availability (software application or custom code)

Not applicable.

References

  1. Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: the task force for the diagnosis and management of chronic coronary syndromes of the European Society of Cardiology (ESC). Eur Heart J. 2020;41(3):407–77.

    Article  Google Scholar 

  2. Patel MR, Dai D, Hernandez AF, Douglas PS, Messenger J, Garratt KN, Maddox TM, Peterson ED, Roe MT. Prevalence and predictors of nonobstructive coronary artery disease identified with coronary angiography in contemporary clinical practice. Am Heart J. 2014;167(6):846–52.

    Article  Google Scholar 

  3. Veterans Administration Coronary Artery Bypass Surgery Cooperative Study Group. Eleven-year survival in the Veterans Administration randomized trial of coronary bypass surgery for stable angina. N Engl J Med. 1984; 311(21):1333–9.

  4. Varnauskas E, European Coronary Surgery Study Group. Twelve-year follow-up of survival in the randomized European Coronary Surgery Study. N Engl J Med 1988; 319(6):332–7.

  5. CASS Principal Investigators and Their Associates. Myocardial infarction and mortality in the coronary artery surgery study (CASS) randomized trial. N Engl J Med. 1984;310(12):750–8.

    Article  Google Scholar 

  6. Yusuf S, Zucker D, Passamani E, Peduzzi P, Takaro T, Fisher LD, Kennedy JW, Davis K, Killip T, Norris R, Morris C. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet. 1994;344(8922):563–70.

    Article  CAS  Google Scholar 

  7. Braunwald E. Effects of coronary-artery bypass grafting on survival: implications of the randomized coronary-artery surgery study. N Engl J Med. 1983;309:1181–4.

    Article  CAS  Google Scholar 

  8. Podrid PJ, Graboys TB, Lown B. Prognosis of medically treated patients with coronary-artery disease with profound ST-segment depression during exercise testing. N Engl J Med. 1981;305(19):1111–6.

    Article  CAS  Google Scholar 

  9. Grüntzig AR, Senning Å, Siegenthaler WE. Nonoperative dilatation of coronary-artery stenosis: percutaneous transluminal coronary angioplasty. N Engl J Med. 1979;301(2):61–8.

    Article  Google Scholar 

  10. Henderson RA, Pocock SJ, Clayton TC, Knight R, Fox KA, Julian DG, Chamberlain DA, Second Randomized Intervention Treatment of Angina (RITA-2) Trial Participants. Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy. Journal of the American College of Cardiology. 2003 42(7):1161–70.

  11. Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007; 356(15):1503–16.

    Article  CAS  Google Scholar 

  12. BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. New England Journal of Medicine. 2009 360(24):2503–15.

  13. Xaplanteris P, Fournier S, Pijls NH, Fearon WF, Barbato E, Tonino PA, Engstrøm T, Kääb S, Dambrink JH, Rioufol G, Toth GG. Five-year outcomes with PCI guided by fractional flow reserve. N Engl J Med. 2018;379(3):250–9.

    Article  Google Scholar 

  14. Rajkumar CA, Nijjer SS, Cole GD, Al-Lamee R, Francis DP. ‘Faith Healing’and ‘Subtraction Anxiety’in Unblinded Trials of Procedures: lessons from DEFER and FAME-2 for End Points in the ISCHEMIA Trial. Circulation: Cardiovascular Quality and Outcomes. 2018 11(3):e004665.

  15. Soares A, Brown DL. The fallacies of fractional flow reserve. Int J Cardiol. 2020;302:34–5.

    Article  Google Scholar 

  16. Maron DJ, Hochman JS, Reynolds HR, et al. Initial invasive or conservative strategy for stable coronary disease. N Engl J Med. 2020;382(15):1395–407.

    Article  Google Scholar 

  17. Hara H, Serruys PW, Takahashi K, Kawashima H, Ono M, Gao C, Wang R, Mohr FW, Holmes DR, Davierwala PM, Head SJ, Thuijs D, Milojevic M, Kappetein AP, Garg S, Onuma Y, Mack MJ. SYNTAX Extended Survival Investigators. Impact of peri-procedural myocardial infarction on outcomes after revascularization. J Am Coll Cardiol 2020;76:1622–1639.

  18. Silvain J, Zeitouni M, Paradies V, Zheng HL, Ndrepepa G, Cavallini C, Feldman DN, Sharma SK, Mehilli J, Gili S, Barbato E, Tarantini G, Ooi SY, von Birgelen C, Jaffe AS, Thygesen K, Montalescot G, Bulluck H, Hausenloy DJ. Cardiac procedural myocardial injury, infarction, and mortality in patients undergoing elective percutaneous coronary intervention: a pooled analysis of patient-level data. Eur Heart J. 2021;42:323–34.

    Article  CAS  Google Scholar 

  19. Chaitman BR, Alexander KP, Cyr DD, Berger JS, Reynolds HR, Bangalore S, Boden WE, Lopes RD, Demkow M, Piero Perna G, Riezebos RK. Myocardial infarction in the ISCHEMIA trial: impact of different definitions on incidence, prognosis, and treatment comparisons. Circulation. 2021;143(8):790–804.

    Article  Google Scholar 

  20. Pursnani S, Korley F, Gopaul R, Kanade P, Chandra N, Shaw RE, Bangalore S. Percutaneous coronary intervention versus optimal medical therapy in stable coronary artery disease: a systematic review and meta-analysis of randomized clinical trials. Circulation: Cardiovascular Interventions 2012; 5(4):476–90.

  21. Navarese EP, Lansky AJ, Kereiakes DJ, Kubica J, Gurbel PA, Gorog DA, Valgimigli M, Curzen N, Kandzari DE, Bonaca MP, Brouwer M. Cardiac mortality in patients randomised to elective coronary revascularisation plus medical therapy or medical therapy alone: a systematic review and meta-analysis. Eur Heart J 2021; May 18.

  22. Brown DL, Boden WE. Impact of revascularisation on outcomes in chronic coronary syndromes: a new meta-analysis with the same old biases?. Eur Heart J 2021; Jun 10.

  23. Weintraub WS, Spertus JA, Kolm P, Maron DJ, Zhang Z, Jurkovitz C, Zhang W, Hartigan PM, Lewis C, Veledar E, Bowen J. Effect of PCI on quality of life in patients with stable coronary disease. N Engl J Med. 2008;359(7):677–87.

    Article  CAS  Google Scholar 

  24. Mitchell JD, Brown DL. Harmonizing the paradigm with the data in stable coronary artery disease: a review and viewpoint. Journal of the American Heart Association. 2017; 6(11):e007006.

  25. Dagenais GR, Lu J, Faxon DP, Kent K, Lago RM, Lezama C, Hueb W, Weiss M, Slater J, Frye RL, Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Study Group. Effects of optimal medical treatment with or without coronary revascularization on angina and subsequent revascularizations in patients with type 2 diabetes mellitus and stable ischemic heart disease. Circulation. 2011; 123(14):1492–500.

  26. Spertus JA, Jones PG, Maron DJ, O’Brien SM, Reynolds HR, Rosenberg Y, Stone GW, Harrell FE Jr, Boden WE, Weintraub WS, Baloch K. Health-status outcomes with invasive or conservative care in coronary disease. N Engl J Med. 2020;382(15):1408–19.

    Article  Google Scholar 

  27. Crea F, Merz C, Beltrame J. On behalf of the Coronary Vasomotion Disorders International Study Group (COVADIS). Mechanisms and diagnostic evaluation of persistent or recurrent angina following percutaneous coronary revascularization. Eur Heart J: 2019; 40:2455–62.

  28. Li Y, Yang D, Lu L, Wu D, Yao J, Hu X, Long M, Luo C, Du Z. Thermodilutional confirmation of coronary microvascular dysfunction in patients with recurrent angina after successful percutaneous coronary intervention. Canadian J Cardiol. 2015;31(8):989–97.

    Article  Google Scholar 

  29. Ong P, Athanasiadis A, Perne A, Mahrholdt H, Schäufele T, Hill S, Sechtem U. Coronary vasomotor abnormalities in patients with stable angina after successful stent implantation but without in-stent restenosis. Clin Res Cardiol 2014; Jan;103(1):11–9.

  30. Ford TJ, Stanley B, Good R, Rocchiccioli P, McEntegart M, Watkins S, Eteiba H, Shaukat A, Lindsay M, Robertson K, Hood S. Stratified medical therapy using invasive coronary function testing in angina: the CorMicA trial. J Am Coll Cardiol 2018: Dec 11;72(23 Part A):2841–55.

  31. Mesnier J, Ducrocq G, Danchin N, Ferrari R, Ford I, Tardif JC, Tendera M, Fox KM, Steg PG, CLARIFY Investigators. International observational analysis of evolution and outcomes of chronic stable angina: the multinational CLARIFY study. Circulation. 2021 144(7):512–23.

  32. Benson H, McCallie DP Jr. Angina pectoris and the placebo effect. N Engl J Med. 1979;300(25):1424–9.

    Article  CAS  Google Scholar 

  33. Rana JS, Mannam A, Donnell-Fink L, Gervino EV, Sellke FW, Laham RJ. Longevity of the placebo effect in the therapeutic angiogenesis and laser myocardial revascularization trials in patients with coronary heart disease. Am J Cardiol. 2005;95(12):1456–9.

    Article  Google Scholar 

  34. Lauder L, da Costa BR, Ewen S, Scholz SS, Wijns W, Lüscher TF, Serruys PW, Edelman ER, Capodanno D, Böhm M, Jüni P. Randomized trials of invasive cardiovascular interventions that include a placebo control: a systematic review and meta-analysis. Eur Heart J. 2020;41(27):2556–69.

    Article  Google Scholar 

  35. Al-Lamee R, Thompson D, Dehbi HM, Sen S, Tang K, Davies J, Keeble T, Mielewczik M, Kaprielian R, Malik IS, Nijjer SS. Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. The Lancet. 2018;391(10115):31–40.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Not applicable.

Corresponding author

Correspondence to David L. Brown.

Ethics declarations

Competing Interests

The author declares no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Brown, D.L. Optimal Medical Therapy as First-Line Therapy for Chronic Coronary Syndromes: Lessons from COURAGE, BARI 2D, FAME 2, and ISCHEMIA. Cardiovasc Drugs Ther 36, 1039–1045 (2022). https://doi.org/10.1007/s10557-021-07289-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10557-021-07289-6

Keywords

Navigation