Optimal medical treatment—with or without percutaneous coronary intervention—improved quality of life significantly in most patients with stable angina, according to an analysis of the quality of life of patients in the COURAGE trial. But PCI may be worthwhile in patients with treatment-refractory symptoms who are initially treated with medical therapy alone.
The combination of PCI plus optimal medical therapy improved patients' quality of life slightly more than did optimal medical therapy alone. Patients with the most frequent symptoms accrued most of the benefits seen with combination treatment, but these were significant for only 6–24 months.
This quality of life subanalysis of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial “demonstrates that both treatment strategies can have a profoundly positive effect on patients' health status and suggests complementary roles—optimal medical therapy as first-line therapy, with PCI reserved for patients who do not have a response or who have severe baseline symptoms,” Dr. Eric D. Peterson and Dr. John S. Rumsfeld wrote in an editorial accompanying the study (N. Engl. J. Med. 2008;359:751-3).
In the trial, Dr. William S. Weintraub of the Christiana Care Health System, Newark, Del., and his associates in the COURAGE Trial Research Group randomized 2,287 patients to either treatment arm. The patients were required to have stenosis of more than 70% in at least one major epicardial coronary artery, with objective evidence of myocardial ischemia or stenosis of at least 80% in at least one coronary artery and classic angina without provocative testing.
The main findings of COURAGE, presented at the annual meeting of the American College of Cardiology in March 2007 and published simultaneously, showed no difference between PCI plus optimal medical therapy versus optimal medical therapy alone on the primary end point of death or myocardial infarction during the study's median follow-up period of 4.6 years (N. Engl. J. Med. 2007;356:1503-16).
In the present analysis, mean scores on all domains of the Seattle Angina Questionnaire significantly improved in both groups after 1–3 months, and did not change substantially thereafter. The questionnaire measures physical limitations resulting from angina; any recent change in the severity of angina; satisfaction with treatment; and quality of life. After 6–24 months of follow-up, scores on some domains of the 19-item questionnaire had improved significantly more among the patients who underwent PCI. This difference was lost at the final 36-month assessment (N. Engl. J. Med. 2008;359:677-87).
Patients who were treated with medical therapy alone (including patients who did not cross over to undergo PCI) also had “significant and rapid improvement” of scores on the Seattle Angina Questionnaire, which “shows that PCI is not always essential for the relief of symptoms in patients with stable angina,” wrote Dr. Peterson of the Duke Clinical Research Institute, Durham, N.C., and Dr. Rumsfeld of the Denver Veterans Affairs Medical Center.
For the first 6 months of follow-up, a greater percentage of PCI-treated patients had “clinically significant” improvement in the domains of physical limitation, angina frequency, and quality of life than did patients who received medical treatment alone. This difference did not persist beyond 6 months.
Baseline scores on the questionnaire were worse for 68 patients treated with medical therapy alone who crossed over to the other group to undergo PCI within 3 months after randomization, compared with the 895 patients in the trial arm who did not cross over within the first 3 months. The scores of these 68 patients rapidly improved following revascularization, “confirming that some patients have an especially marked benefit from PCI,” Dr. Weintraub and his coinvestigators wrote.
Analyses of the patients who had complete data through 36 months showed that most of the improvement in angina frequency occurred during the first 3 months. PCI-treated patients who had the most frequent angina symptoms (multiple episodes of angina per week) had the largest clinical improvement in that period. No improvement occurred among patients who rarely had angina.
During the first 24 months of follow-up, a significantly greater proportion of patients who received PCI and optimal medical therapy were totally free from angina symptoms, compared with those who received optimal medical therapy alone. (See box.) But this result was driven by patients with the most frequent angina symptoms.
In comparison with optimal medical therapy alone, Dr. Weintraub and his colleagues calculated that 11–17 patients would have to be treated with PCI plus optimal medical therapy in order for 1 patient to obtain a clinically significant improvement in angina frequency, physical function, or quality of life.
But this calculation does not take into account the harms associated with PCI, according to Dr. Peterson and Dr. Rumsfeld. The current in-hospital mortality associated with elective PCI is about 0.2%, based on data from the National Cardiovascular Data Registry. The periprocedural rate of myocardial infarction in the COURAGE trial was 2.8%. Based on the calculations of the COURAGE trial investigators and these figures, “for every 1,000 patients treated with a PCI-first strategy, approximately 2 would die, 28 would have a periprocedural myocardial infarction, 60 to 90 would have an incremental, transient gain in health status, and 800 or more would see neither harm nor benefit,” Dr. Peterson and Dr. Rumsfeld wrote. This estimation makes it “difficult to assert that a PCI-first strategy should clearly be adopted routinely in patients with stable angina.”