These results have spawned considerable attention, and at times, controversy, over the way that we treat patients with stable coronary artery disease.
Presenters: William E. Boden, MD (Buffalo General Hospital, Buffalo, New York), and William S. Weintraub, MD (Christiana Care Health System, Newark, Delaware)
Introduction
More than 1 million percutaneous coronary interventions (PCIs) are performed in the United States each year, the great majority of which are performed electively in patients with stable coronary artery disease. PCI in patients with acute coronary syndrome (ACS) has been shown to reduce the incidence of death and myocardial infarction (MI). However, the effects of PCI in patients with stable coronary artery disease have not been well studied, with prior studies in this patient population suggesting that PCI only reduces the frequency of angina and improves short-term exercise performance with no impact on mortality.
Study Design
The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE)[1] trial was a multicenter, randomized, controlled trial that compared a strategy of PCI plus optimal medical therapy (OMT; PCI group) vs OMT alone in patients with stable coronary artery disease. The trial was designed with 2 hypotheses.
Primary: PCI would reduce all-cause mortality or nonfatal MI relative to OMT alone.
Secondary: PCI would yield superior outcomes related to resource utilization and quality-of-life outcomes.
Patients were randomized to PCI or to OMT alone and followed for 2.5-7.0 years (mean, 4.6 years). Patients with 1-, 2-, or 3-vessel disease (> 70% visual stenosis of proximal segment), with anatomy suitable for PCI, and Canadian Cardiovascular Society (CCS) class I-III angina were enrolled in the study. Patients with unstable angina, post-MI, revascularization within the last 6 months, cardiogenic shock, or heart failure were excluded.
Primary endpoint: Death or nonfatal MI.
Secondary endpoints:
Death, MI, or stroke;
Hospitalization for biomarkers;
Cost, resource utilization;
Quality of life, including angina; and
Cost-effectiveness.
Patient Population
A total of 2287 patients screened at 50 centers in the United States and Canada were randomized to PCI (n = 1149) or to OMT (n = 1138). All patients were treated with antiplatelet therapy with aspirin (81-325 mg/day) or 75 mg/day of clopidogrel. In addition, all patients were treated with aggressive lipid-lowering therapy with simvastatin alone or in combination with ezetimibe. Baseline clinical and angiographic characteristics were well balanced between the 2 groups ( Table 1 ). More than half of all patients in the PCI arm were treated with 1 stent and 41% received ≥ 2 stents.
COURAGE: Primary Hypothesis -- Effects on Mortality and Nonfatal MI
Dr. Boden presented the results of the primary hypothesis of the trial evaluating the effects of PCI vs OMT alone on mortality and nonfatal MI.
After a mean follow-up of 4.6 years, there was no difference in the rate of freedom from death of any cause or nonfatal MI between the PCI and OMT-alone groups (19.0% vs 18.5%, respectively; P =62). There were also no differences in the individual rates of all-cause mortality, MI, stroke, or hospitalization for ACS ( Table 2 ) The number of patients in the PCI group who underwent revascularization was significantly lower than the number of first procedures performed in the OMT group, at an average of 10 and 11 months, respectively (21.1% vs 32.6%; P <001). In addition, freedom from angina was higher in the PCI group than OMT alone at 1- and 3-year follow-up; by 5 years, the rates were similar between the 2 groups (Figure 1).
Figure 1.
COURAGE: freedom from angina at 1-, 3-, and 5-year follow-up.
Primary Hypothesis: Conclusions
As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk for death, MI, or other major cardiovascular events when added to OMT.
PCI resulted in better angina relief during most of the follow-up period, but OMT was also effective, with no between-group difference in angina-free status at 5 years.
These findings reinforce existing clinical practice guidelines, which state that PCI can be safely deferred in patients with stable coronary artery disease, even in those with extensive, multivessel involvement and inducible ischemia, provided that intensive, multifaceted OMT is instituted and maintained.
OMT and aggressive management of multiple treatment targets without initial PCI can be implemented safety in the majority of patients with stable coronary artery disease, two thirds of whom may not require even a first revascularization during long-term follow-up.
COURAGE: Secondary Hypothesis -- Health Status and Economic Outcomes
Dr. Weintraub presented the results of the health status and economic analyses of the COURAGE study.
Quality of life was assessed with 3 different questionnaires :
The Seattle Angina Questionnaire (SAQ);
RAND 36-Item Health Survey; and
Utility by Standards Gamble.
Data were collected at 1, 3, 6, and 12 months, and then annually.
At baseline, there was no difference between the 2 groups in SAQ scores that measured physical limitations, angina frequency, and quality of life. However, evidenced as early as 3 months and sustained out to 36 months, patients in the PCI group had higher SAQ scores, suggesting improved status in all measures studied (Figure 2). RAND 36 scores were higher in the PCI group, but by 24 months, the difference was not significant (Figure 2).
Figure 2.
COURAGE: Seattle Angina Questionnaire and RAND 36-Item Health Survey scores over 36-month follow-up.
The economic cost analysis compared resource utilization and costs between the 2 groups. An incremental cost-efficacy analysis was also performed, which was calculated as the additional cost of PCI divided by the gain in life-years and quality-adjusted life-years (QALYs).[2] QALYs were calculated by multiplying survival by utility.
At each follow-up period, cost data were significantly lower with OMT alone than with PCI (P <0001) ( Table 3 ). There was no difference in utility between the 2 groups at any time during follow-up. The difference in calculated QALYs between the 2 groups was 0.024, equating to approximately 8 days. This difference translated into a cost of $217,000 per QALY gained. Given that the cost-effective benchmark for such therapies is $50,000, the overall cost of QALY gained suggests that PCI would only be considered a cost-effective approach in < 1% of patients.
Secondary Hypothesis: Conclusions
Compared with OMT alone, PCI plus OMT is associated with improved quality-of-life measures over long-term follow-up.
PCI plus OMT as a first-choice therapy for stable coronary artery disease is not cost-effective compared with OMT alone.
Viewpoint
COURAGE is a landmark trial that provides important data in stable angina patients with coronary artery disease. The results reinforce the current guidelines that state that in selected patients OMT can be as effective and as safe as PCI in the prevention of hard endpoints, such as death, MI, and stroke. However, in this study, PCI provided better anginal relief in the initial years of follow-up.
In addition, the secondary hypothesis of the study, evaluating quality of life and cost-effectiveness, provides important additional information on how we treat our patients. The aforementioned analysis showed that PCI on top of OMT does a better job in controlling physical limitation, angina, and improves quality of life, but at a significantly higher cost.
These results have spawned considerable attention, and at times, controversy, over the way that we treat patients with stable coronary artery disease. The results are telling, but are they sufficiently conclusive to deny early PCI in all stable patients? Certainly, we must always consider each patient on an individual basis.
Medscape Cardiology © 2007 Medscape
Cite this: COURAGE: Revascularization and Aggressive Drug Evaluation in Stable Coronary Artery Disease -- Mortality, Quality of Life, and Cost-Effectiveness - Medscape - May 01, 2007.
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