This outcome should have been no surprise. The only surprise is that many in the medical and lay public were surprised to learn that the life-saving benefits of PCI for acute coronary syndromes did not transfer to the stable angina patient. An erroneous but previously widely-held belief was that mechanical lumen enlargement (i.e., stenting) for stable, focal CAD would save lives over medical therapy alone. The COURAGE Trial1 was widely touted in the media as a study demonstrating there was too much angioplasty and unnecessary stenting. I believe that this is not true to a large extent, as does Dr. Dehmer. However, the COURAGE trial, as Dr. Boden emphatically mentions, indicates that some of the patients stented would likely have done as well with fewer stents (or perhaps no stents) and more intensive medical treatment. This is the most important take-home message from the COURAGE trial.

Points of interest when reviewing the trial should be kept in mind. COURAGE was conducted from 1999 to 2004, involving 50 U.S. and Canadian medical centers. It screened 35,000 patients and found only 3071 eligible to participate, with only 74% (2287) ultimately enrolled. Randomized to the PCI group were 1149 patients, with 1138 patients randomized to the medical therapy group. The study was well-conducted, with the two patient groups matched for age, sex, ethnic origins, severity and duration of angina, and history of coexisting morbidities, including hypertension, diabetes, heart failure, MI, cardiovascular anomalies (CVA), prior coronary artery bypass grafting (CABG), and prior PCI. Ischemic testing was present in equal proportion between the groups, and involved both single and multiple reversible defects on nuclear perfusion imaging. The severity of CAD differed only in regard to the presence of proximal left anterior descending coronary artery (LAD) disease, which was more prevalent in the medical therapy group. At the 5-year follow-up, no difference in death or MI in the PCI group (19% versus 18.5%, P=NS) was observed. Also note that not every patient remained in the assigned group (i.e., cross-over), although they were correctly analyzed by the initial intention to treat. Revascularization with PCI or CABG occurred more in the medical than the PCI group (32.6% versus 21.1% for the PCI group). Dr. Boden notes that DES would likely not have altered these results even if they had been available over the study period.

This trial did not surprise the interventionalists as much as the press and general medical community. Prior studies comparing PCI to medical therapy showed PCI provided better symptom relief, reduced medication use and increased exercise tolerance over medical therapy alone. As shown by COURAGE, PCI does not reduce myocardial infarctions, very likely due to the diffuse nature of atherosclerosis, with activated plaque causing infarction despite treatment of angina-producing severe lesions. There are more than 10 times as many mild non-obstructing plaques as severe plaques in most CAD patients.

Dr. Dehmer provides insight to the management of patients with CAD in light of the COURAGE trial. He reminds us that medications and lifestyle modification alone may not overcome the life limiting aspects of angina in at least 1/3 of patients. Stenting does reduce the amount of medication needed and improves the quality of a person's life despite having no major impact on longevity.

How applicable are the results of COURAGE to the larger population of CAD patients?

The COURAGE trial excluded 90% of CAD patients for a variety of good reasons, focusing only on the stable, intermediate-risk individuals. Dr. Boden feels that this was a higher-risk CAD subset, but selecting only 10% of patients from a broad population might question this. It can be casually said that the results are not applicable to the majority of CAD patients who have complex presentations and co-morbidities. However, if COURAGE had included all patients with coronary artery disease, the results might not be as powerful, since the study population would have been uncontrolled. Dr. Dehmer puts this issue into perspective for us.

Did some lesions receive stents that could have just as well been treated medically?

This issue is also very likely, since recent studies (Ragosta et al2) point to the disparity between ischemic testing in multivessel disease patients as well as the well-known disparity between physiology (e.g., fractional flow reserve, or FFR) and angiography (Sant'Anna et al3). Using current methods such as FFR, selective intervention for only those lesions which are truly ischemic-producing can be performed to obtain COURAGE-like results. Medical therapy over intervention (for lesions which are physiologically normal) is also supported by COURAGE, with selectively-employed PCI for patients with refractory (to medical treatment) angina. This approach may be the best option for all.

To take a quote from Dr. Dehmer at the press conference on release of the COURAGE trial, The results of COURAGE remind us that medicine is a dynamic art. We base practice on evidence we learned at one time and alter it based on additional evidence accumulated at another. The COURAGE trial should not be viewed as a battle between intervention and medicine; rather, an attempt to identify the additional benefit of mechanical opening of selected lesions in the setting of systemic medical therapy for atherosclerosis.