Review article
Management of stable patients with coronary heart disease: Clinical implications of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial

https://doi.org/10.1016/j.jacl.2007.10.009Get rights and content

Abstract

Early coronary revascularization has been shown to reduce major adverse cardiovascular events in patients with acute coronary syndromes. In patients with stable coronary heart disease (CHD), however, coronary revascularization does not reduce death or myocardial infarction compared to intensive medical therapy. The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial was the first to study whether coronary revascularization performed in addition to medical therapy, rather than as an alternative, would reduce death or myocardial infarction in patients with stable CHD. Between 1999 and 2004, 2287 patients were enrolled in 50 centers throughout Canada and the United States. After a median follow-up of 4.6 years, revascularization performed in addition to intensive medical therapy did not result in reduced mortality or myocardial infarction compared to medical therapy alone. At the end of follow-up, anginal control was similar in both groups, although patients receiving medical therapy only did require more antianginal medications, and one-third ultimately required revascularization. We review the strengths, limitations, and clinical relevance of the COURAGE trial in the context of the current literature on the benefits of medical management and coronary revascularization in patients with stable CHD.

Section snippets

The COURAGE trial

The COURAGE trial7 was conducted in 50 centers throughout Canada and the United States, including both Veterans Administration and non–Veterans Administration hospitals. Individuals were enrolled if they had at least one proximal epicardial coronary artery stenosis of ≥70% and objective evidence of myocardial ischemia (≥1 mm of ST-segment depression or ≥2 mm of T-wave inversion on a electrocardiogram at rest or inducible ischemia on exercise or pharmacologic stress testing). Individuals with at

Evidence for revascularization

To fully understand the implications of the COURAGE trial, we must first examine the known benefits of revascularization and medical therapy. Previous trials have established the efficacy of coronary revascularization in certain high-risk populations with coronary artery disease (CAD). In the 1970s and 1980s, the benefits of CABG surgery over medical therapy for CAD were evaluated in the Veterans Affairs Cooperative Study of Coronary Artery Bypass Surgery,10 the Coronary Artery Surgery Study,11

Evidence for medical therapy

The ACC/AHA guidelines4 divide therapies for CAD into two categories: (1) antianginal and anti-ischemic therapy, and (2) treatments that reduce death and myocardial infarction. Beta blockers are the preferred first-line antianginal agents, as they reduce mortality in patients with a recent myocardial infarction.17 In addition to β blockers, calcium channel blockers and nitrates are recommended to decrease anginal symptoms and ischemia, if necessary.

To reduce the risk of death or myocardial

Incremental benefit of revascularization in addition to medical therapy

Given these data, why did PCI, when used in addition to intensive medical therapy in the COURAGE trial, fail to provide an incremental reduction in death or myocardial infarction beyond that provided by medical therapy? For PCI to prevent myocardial infarction, the lesion targeted by the intervention must be likely to result in a myocardial infarction if not intervened upon. However, because the majority of myocardial infarctions result from acute rupture of previously nonobstructive lesions

Strengths and limitations of the COURAGE trial

Many have argued that participants in COURAGE represent a highly select group of patients with CAD who are not representative of the typical CAD patient seen in United States cardiology practices. Wharton et al8 stated that, based on their interpretation of data from New York State, only approximately one-third of patients who have undergone PCI have truly stable CAD. Furthermore, they state that many patients with stable CAD would still have been excluded from COURAGE for other high-risk

Conclusions

The COURAGE trial demonstrated that on average, patients with stable CAD, who represent at least half of the US population with CHD,45 can be safely and effectively managed with an initial strategy of intensive medical therapy, reserving revascularization for patients with persistent or progressive symptoms. None of the subgroups analyzed, including diabetics and patients with multivessel disease, appeared to benefit from early, routine revascularization. It is important to note, however, that

Acknowledgment

Dr. Brown’s position is supported in part by grant number 5 T32 HS013852 from the Agency for Healthcare Research and Quality, Rockville, MD.

References (53)

  • L.J. Shaw et al.

    Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

    J Nucl Cardiol

    (2006)
  • D.J. Kereiakes et al.

    The truth and consequences of the COURAGE trial

    J Am Coll Cardiol

    (2007)
  • W. Rosamond et al.

    Heart Disease and Stroke Statistics–2007 UpdateA report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee

    Circulation

    (2007)
  • E.M. Antman et al.

    ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction)

    (2004)
  • R.J. Gibbons et al.

    ACC/AHA 2002 guideline update for the management of patients with chronic stable angina: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for the Management of Patients with Chronic Stable Angina). 2002

  • G.A. Lin et al.

    Cardiologists’ use of percutaneous coronary interventions for stable coronary artery disease

    Arch Intern Med

    (2007)
  • W.E. Boden et al.

    Optimal medical therapy with or without PCI for stable coronary disease

    N Engl J Med

    (2007)
  • T.P. Wharton et al.

    PCI for stable coronary disease

    N Engl J Med

    (2007)
  • D.G. Katritsis et al.

    Percutaneous coronary intervention versus conservative therapy in nonacute coronary artery disease: a meta-analysis

    Circulation

    (2005)

  • Eleven-year survival in the Veterans Administration randomized trial of coronary bypass surgery for stable angina

    N Engl J Med

    (1984)

  • CASS: a randomized trial of coronary bypass surgery

    Circulation

    (1983)
  • E. Varnauskas

    Twelve-year follow-up of survival in the randomized European Coronary Surgery Study

    N Engl J Med

    (1988)

  • Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease

    N Engl J Med

    (1996)

  • Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease: the Bypass Angioplasty Revascularization Investigation (BARI)

    Circulation

    (1997)
  • N. Freemantle et al.

    Beta blockade after myocardial infarction: systematic review and meta regression analysis

    BMJ

    (1999)

  • Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients

    N Engl J Med

    (2000)

    • Cited by (6)

    • Circulating levels of sgp130 and sex hormones in male patients with coronary atherosclerotic disease

      2017, Atherosclerosis
      Citation Excerpt :

      A total of 376 male patients were divided into the CHD group (254 cases) and control group (122 cases) according to the coronary angiography. Individuals with more than 30% occlusion of at least one major coronary artery were diagnosed with CHD [26]; while control subjects who had symptoms of chest pain and tightness exhibited completely normal coronary arteries. Based on the diagnosis standards of CHD [27], 254 CHD cases were divided into three subgroups: stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI).

    • Achievement of optimal medical therapy goals for U.S. adults with coronary artery disease: Results from the REGARDS Study (REasons for Geographic and Racial Differences in Stroke)

      2014, Journal of the American College of Cardiology

    • The roles of a novel anti-inflammatory factor, milk fat globule-epidermal growth factor 8, in patients with coronary atherosclerotic heart disease

      2014, Atherosclerosis
      Citation Excerpt :

      All of the subjects received coronary angiography. Individuals found to have >30% occlusion of at least one major coronary artery were defined as having CHD (cases); while those with completely normal coronary arteries and with ≤30% occlusion in all coronary arteries (free of significant stenosis) constituted the control group [9]. According to the CHD diagnosis standards [10], we divided the cases into three subgroups: stable angina (SA), unstable angina (UA), and acute myocardial infarction (AMI).

    • Serum cystatin C and the risk of coronary heart disease in ethnic Chinese patients with normal renal function

      2016, Lab Medicine

    • The RIDA allergy screen versus the phadiatop test in 430 consecutive patient specimens

      2016, Lab Medicine

    • Estradiol/testosterone imbalance: Impact on coronary heart disease risk factors in postmenopausal women

      2012, Cardiology (Switzerland)
    View full text
    Copyright © 2007 National Lipid Association. Published by Elsevier Inc. All rights reserved.