The results of one of the more remarkable studies from the meeting of the American College of Cardiology were presented on Monday, along with the simultaneous early publishing of the study online in the New England Journal of Medicine. As a result the study results captured a front page article in today’s New York Times.
The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial was a randomized trial involving 2287 patients with stable but significant coronary artery disease who were randomized to either undergo PCI (using bare metal stents) or to receive optimal medical therapy alone. The primary outcome of the study was a composite outcome of death from any cause and non-fatal myocardial infarction. During a mean follow up of 4.6 years, there were no significant differences between the PCI group and the medical-therapy group in the primary event rate (19% in the PCI group, 18.5% in the medical therapy group, P=0.62). Secondary endpoints included hospitalization for acute coronary syndrome, stroke, rates of MI and death. All secondary outcomes and individual components of the primary outcomes showed no significant differences between the study groups. Although there was a statistically significant difference in the rate of patients who were free from angina between the study groups at 1 and 3 years, this difference was not significant at baseline or at 5 years of follow-up. 74% of patients who had undergone PCI were angina-free at 5 years, compared with 72% of those who had received medical therapy (P=0.35). Revascularization was performed at the discretion of the patient’s physician due to worsening ischemia or refractory angina, and rates of revascularization were significantly higher in the medical-therapy group (21.1 % versus 32.6%, P<0.001).
The patients enrolled in this study, which occurred between 1999 and 2004, were mostly white males with stable coronary artery disease (as documented by ST depression or T wave inversion on resting ECG, inducible ischemia with exercise or pharmacological stress, or at least one coronary artery stenosis of at least 80% and classic angina). Two thirds of the patients had multi-vessel disease. Patients with refractory heart failure or an ejection fraction less than 30%, recent revascularization, or a markedly positive stress test were excluded. Both of the study groups received optimization of medical therapy, including aspirin along with aggressive lipid and blood pressure lowering.
The results from the study are surprising and somewhat unexpected. The authors of the study explain their results, in part, by the physiologic differences between vulnerable plaques which rupture and are associated with acute coronary syndromes and more fibrous plaques that can cause luminal narrowing and anginal symptoms in patients with stable disease such as those in enrolled in this study.
In summary, this study reveals that PCI offers no benefit over aggressive medical management when performed in patients with stable coronary artery disease, and suggests that PCI may be deferred in patients with stable disease as long as medical therapy is optimized and maintained. It’s a ground-breaking study that challenges our current practice and harbors tremendous clinical implications and is certain to generate much controversy.
Boden WE et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med 2007 Mar 27; [pub ahead of print]. (http://content.nejm.org/cgi/content/short/NEJMoa070829)