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Medicine or PCI for Stable CAD: Use COURAGE

Disclosure: None
Pub Date: Thursday, May 3, 2007
Authors: Morton J. Kern, MD, FAHA 
Article: Medicine or PCI for Stable CAD: Use COURAGE

Citation

Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR, Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC, Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS.,  Optimal medical therapy with or without PCI for stable coronary disease.,  The New England journal of medicine,  356 (15) 1503-16. View in PubMed

Article Text

A previously wide-held belief that simple lumen enlargement using percutaneous coronary intervention (PCI, e.g., stenting) for stable coronary artery disease (CAD) would save lives over medical therapy alone was recently dispelled by the COURAGE trial.[1]

Boden and colleagues [1] asked whether optimal medical therapy with aggressive lifestyle and CAD risk factor modification alone is superior to optimal medical therapy plus PCI in reducing the risk of cardiovascular events over a 5-year period. Conducted from 1999 to 2000 in 50 U.S. and Canadian medical centers, the study screened 35,000 patients to find 3071 who met eligibility criteria, of whom 74% were entered into the protocol. The 2287 enrolled patients were randomized, 1149 to PCI and 1138 to optimal medical therapy. About 100 patients were lost to follow-up for each group, and the remaining patients were followed for primary endpoints over 5 years.

The two patient groups were well matched for age, sex, ethnic origins, severity and duration of angina, and history of coexisting morbidities, including hypertension, diabetes, heart failure, myocardial infarction (MI), cardiovascular accident (CVA), prior coronary artery bypass graft (CABG), and prior PCI. Ischemic testing was present in equal proportions 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 LAD disease, which was more prevalent in the medical therapy group.

The clinical outcome over the 5-year period showed no difference in death or MI between the PCI and medical groups (19% vs. 18.5%, p = NS). There was a similar proportion of hospitalizations for acute coronary syndrome (ACS) in both groups (12.4% vs. 11.8%), and total nonfatal MIs, including periprocedural infarctions, were equivalent (13.2% vs. 12.3%). There was a greater need for revascularization with PCI or CABG in the medical group (32.6% vs. 21.1% for the PCI group). The study concludes that, in patients with stable CAD receiving optimal medical management, the addition of PCI did not reduce the risk of death, MI, or other major cardiovascular events over 5 years.

Although it has long been known that PCI does not reduce death or MI in nonacute patients [2], the medical community and lay press were surprised to be reintroduced to this fact after many years of experiencing superior results from interventional cardiology, treating our most critically ill patients with great success. It was always the hope that the mortality benefits of PCI for ACS and acute MI (AMI) patients could be transferred to others. As shown in earlier studies [2] and again by COURAGE, this is not the case.

Why does PCI not reduce the incidence of AMI in stable CAD? The reason for this lies in the natural history of atherosclerosis. The diffuse distribution of CAD provides a milieu of numerous nonobstructive plaques that have the propensity to activate and evolve into acute obstructive lesions producing acute coronary syndromes, including MI. Despite excellent resolution of obstructions by coronary stenting, the few isolated proximal angina-producing obstructions are far outnumbered by the many nonobstructive luminal narrowings with the potential to activate and thrombose. This aspect of CAD is a problem that cannot be resolved by PCI. In fairness, it should be said that medications and lifestyle modifications alone may not overcome the life-limiting aspects of angina. PCI improves the quality of a person's life despite having no major impact on longevity [3], and for this, more than almost any other reason, PCI remains part of everyday cardiology practice.

The major obstacles in using more "COURAGE" to treat CAD are (1) the cardiologists' bias toward angiography and (2) the unknown results in the large number of patients with CAD (>32,000) who did not qualify to enter the study. Cardiologists have a long-standing and intuitive bias toward using the angiogram as an indicator of CAD and its prognosis. A common dilemma faced by a treating physician is the management of an asymptomatic middle-aged patient with a 75% proximal left anterior descending stenosis with abnormal stress test results. It is a rare interventionalist who can resist the urge to stent this lesion to not only relieve ischemia (silent or symptomatic) but also, and perhaps wishfully, to prevent the potentially life-threatening anterior infarction. The "oculostenotic reflex" (i.e., treating by angiography alone) is so powerful that routine stenting has become ingrained in the treatment of CAD.

Given the results of medical therapy, does COURAGE indicate that there was an excess of stenting? This is difficult to determine, but it is possible that some lesions did not benefit (nor were they harmed) by stenting. Angiography has well-known limitations for the determination of ischemia, especially for intermediately severe lesions, which comprise many of the multivessel lesions.[4] Stenting lesions that were not flow limiting would not produce either anti-ischemic or survival benefit over medical therapy alone. It is possible to perform selective intervention for only those lesions that are truly ischemia producing by using in-lab functional testing (e.g., fractional flow reserve [5]), producing outcomes equivalent to CABG of all lesions.[6] Medical therapy over intervention (for lesions that are physiologically normal) is also supported by studies describing selectively employed FFR-guided PCI. Such an approach may be the best option for use of PCI in MV patients.[7]

How applicable are the results of COURAGE to the larger population of CAD patients? To answer a specific question, the COURAGE study excluded 90% of CAD patients for a variety of good reasons, focusing only on the stable intermediate-risk individuals. In so doing, it can be said that the results are not applicable to the majority of CAD patients who have comorbidities associated with CAD. On the other hand, should enrollment have included all patients with CAD, critics would likely say that the results would not be applicable due to the uncontrolled nature of the study population. Nonetheless, the question of whether PCI was of long-term benefit to stable angina patients without active syndromes, severe comorbidities, valvular heart disease, and so on was well addressed.

The real surprise of COURAGE is that anyone was indeed surprised. Stable CAD, by virtue of its diffuse nature, will continue to cause morbidity even after complete coronary revascularization. (Recall studies showing that CABG, like PCI, does not reduce MI rates.) The medical and lay community may have been inadvertently misled to believe that the benefits of primary PCI in AMI would be transferred to patients with stable CAD. However, in the absence of data to the contrary, interventional cardiology continues to address CAD outcomes in the 90% of CAD patients not yet addressed by the COURAGE study design.

The COURAGE trial should not be viewed as a battle between intervention and medicine but rather as an attempt to identify the additional benefit of revascularizing selected regions in the setting of systemic medical therapy for atherosclerosis.

References

  1. Boden WE, et al. Optimal medical therapy with or without PCI for stable coronary artery disease. N Engl J Med 2007;356:1503-1516.
  2. Katritsis DG, Ioannidis JPA. Percutaneous coronary intervention versus conservative therapy in nonacute coronary artery disease: a meta-analysis. Circulation 2005;111:2906-2912.
  3. Parisi AF, Folland ED, Hartigan P. A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. N Engl J Med 1992;326:10-16.
  4. Sant'Anna F, Silva E, et al. Influence of routine assessment of fractional flow reserve on decision making during coronary interventions. Am J Cardiol 2007;99:504-508.
  5. Ragosta M, Bishop A, et al. Comparison between angiography and fractional flow reserve versus single-photon emission computed tomographic myocardial perfusion imaging for determining lesion significance in patients with multivessel coronary disease. J Am Cardiol 2007;896-902.
  6. Berger A, Kees-Joost B, et al. Long-term clinical outcome after fractional flow reserve-guided percutaneous coronary intervention in patients with multivessel disease. J Am Coll Cardiol 2005;46:438-442.
  7. Kees-Joost B, Nico HJ, et al. Percutaneous coronary intervention or bypass surgery in multivessel disease? Catheter Cardiovasc Interv 2004;63:184-191.

-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association. --