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Should patients with stable ischemic heart disease undergo revascularization?

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The answer is less clear for these patients than for patients with acute coronary syndromes. In the latter group, percutaneous or surgical revascularization reduces the rates of morbidity and mortality, whereas in patients with stable ischemic heart disease, benefits may be limited to the improvement of angina. Certain markers and criteria may help us in this decision, and trials are ongoing.

Of importance, all patients with coronary artery disease should receive guideline-directed medical therapy as tolerated, regardless of whether they undergo revascularization.


In all the relevant trials, patients with stable ischemic heart disease in both the revascularization groups and the unrevascularized groups received guideline-directed medical therapy. Current guidelines1 give class I recommendations (ie, treatment should be given) for:

  • Lipid management
  • Blood pressure management
  • Physical activity
  • Weight management
  • Smoking cessation
  • Antiplatelet therapy
  • Beta-blockers for patients with normal left ventricular function after an acute coronary syndrome event, and for those with an ejection fraction of 40% or less
  • Angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for patients who have hypertension, diabetes mellitus, a left ventricular ejection fraction of 40% or less, or chronic kidney disease
  • Annual influenza vaccination
  • Anti-ischemic medications (beta-blockers, calcium channel blockers, nitrates) for relief of symptoms.


Results of the studies outlined below will help in deciding when to use guideline-directed medical therapy alone or medical therapy plus revascularization.

COURAGE trial: No added benefit in patients at low risk

The findings of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE), published in 2007, suggested that in select patients, percutaneous coronary intervention for stable coronary artery disease was no better than guideline-directed medical therapy alone for reducing the outcomes of death, myocardial infarction, or hospitalization for acute coronary syndrome.2

Of note, however, is that the 2,287 patients included in COURAGE were a low-risk subset of the more than 35,000 patients initially evaluated. The investigators reviewed the patients’ coronary angiograms before enrollment, and thus many patients with complex or high-risk anatomy were likely excluded based on an a priori assessment of angiographic images.

Also, coronary stent technology has substantially improved since COURAGE (which primarily used bare-metal stents and early drug-eluting stents), and this brings into question whether the results are applicable to current patients.

Moreover, in subsequent substudies from COURAGE, revascularization significantly improved symptoms of angina and quality-of-life scores compared with medical therapy alone.3,4

Also important is that more than one-third of the patients in the medical therapy group crossed over to revascularization during the study, most often for worsening symptoms of angina.

Regardless of its limitations, COURAGE played an important role in delineating the use of guideline-directed medical therapy alone in certain low-risk patients and sparked debate about when and if to revascularize other patients.

BARI 2D trial: CABG may benefit those with diabetes

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, published in 2009, aimed to find out if revascularization in patients with stable ischemic heart disease and diabetes was beneficial compared with medical therapy alone.5

While it was not designed to directly compare percutaneous coronary intervention vs coronary artery bypass grafting (CABG), it did find that medical therapy plus CABG might reduce the rate of adverse cardiovascular events in this population compared with medical therapy alone or medical therapy plus percutaneous intervention.

As with COURAGE, however, the patients in the medical therapy group in BARI 2D also had a high rate of crossover to revascularization, primarily driven by worsening anginal symptoms.

FREEDOM and the 2014 updated guideline

Based on the findings of BARI 2D and those of FREEDOM (Future Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of Multivessel Disease),6 the American College of Cardiology and American Heart Association updated their recommendations in 2014.7 This focused update states that for patients with diabetes and multivessel coronary artery disease, if revascularization is likely to improve survival (for example, in three-vessel disease or complex two-vessel disease involving the proximal left anterior descending artery), then CABG should be performed if a left internal mammary artery graft can be anastomosed to the left anterior descending artery. Otherwise, percutaneous coronary intervention should be reserved for those patients with diabetes and high-risk or complex multivessel coronary artery disease who are not good surgical candidates.

FAME 2 trial: Fractional flow reserve as a guide

The Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 2 (FAME 2) trial,8 published in 2012, evaluated whether clinical outcomes differ between patients who undergo percutaneous revascularization plus medical therapy and those who are treated with medical therapy alone, using fractional flow reserve as a means to determine which stenoses should be considered for intervention. Fractional flow reserve performed during invasive angiography determines the ratio of intracoronary pressure to aortic pressure using a wire advanced across a coronary obstruction.

FAME 2 found a markedly lower incidence of the primary composite end point of death, myocardial infarction, and urgent revascularization with randomization to percutaneous revascularization plus medical therapy compared with medical therapy only (4.3% vs 12.7%, P = .001) in patients with a fractional flow reserve less than 0.80 (considered a hemodynamically significant obstruction). The trial was stopped early because of the markedly different outcomes.

Of note, however, the reduction in adverse clinical outcomes was driven primarily by a reduction in urgent revascularizations in those treated with percutaneous coronary intervention in the revascularization arm. Regardless, using fractional flow reserve to guide whether obstructive coronary lesions should be treated with percutaneous coronary intervention has appropriately become a mainstay in interventional cardiology.

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