Cost-Effectiveness of Diagnostic Strategies for Patients with Chest Pain

Coronary artery disease continues to be the leading cause of death in the United States. Approximately 500000 patients receive a new diagnosis of coronary artery disease each year, 47% of whom will have angina as their initial event (1). The prevalence of coronary artery disease in patients who present with typical angina is 93% for men and 72% for women; approximately 48% of these patients have triple-vessel or left main coronary artery disease (2). Even for patients who present with nonspecific chest pain, the prevalence of coronary artery disease can be as high as 27% (for example, among 65-year-old men) (2). Selective use of revascularization with coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA) can improve both the prognosis and the health-related quality of life of many patients. For patients who present with chest pain, many noninvasive tests can be used to determine whether they should undergo coronary angiography. Exercise electrocardiography is widely used and has a demonstrated sensitivity and specificity of 68% and 77%, respectively (3). Adjunctive imaging techniques, such as echocardiography or single-photon emission computed tomography (SPECT), improve the overall diagnostic performance of the exercise test, although at higher cost. The routine use of coronary angiography without previous noninvasive testing is typically not advocated because of the associated risk for morbidity and death and its relatively high cost. From a health care policy perspective, the value of diagnostic test strategies for patients with chest pain should reflect not only the diagnostic accuracy, risk, and cost of the test but also the probability that the patient has significant coronary artery disease, the costs of further testing or treatments that may be induced by the test result, the costs of events that may be averted by subsequent treatment, and the health-related quality of life associated with various degrees of chest pain. We constructed a decision-analytic model to evaluate the cost-effectiveness of various diagnostic strategies for patients with chest pain from a health care policy perspective (4). We extend the work of a previous cost-effectiveness analysis of exercise electrocardiography in patients with chest pain (5) by including two widely used noninvasive tests that are often the initial test selected in current clinical practice: exercise echocardiography and exercise SPECT. Methods We evaluated cohorts of patients stratified by decade of age (40 to 49 years, 50 to 59 years, or 60 to 69 years), sex, and characteristics and severity of chest pain. Three types of chest pain were considered: typical angina (substernal chest pain that is exertional in nature and is relieved promptly by nitroglycerin therapy), atypical angina (pain with two of the three characteristics of typical angina), and nonspecific chest pain (pain with no more than one of the three characteristics of typical angina). We assumed that the severity of chest pain was either mild or severe. Because most of the available data applied to men 50 to 59 years of age, this demographic population was used in the base-case analyses. Decision-Analytic Model We constructed a decision-analytic model to evaluate various diagnostic work-up scenarios for patients who present with chest pain, have no history of myocardial infarction, and are able to perform an exercise stress test. We used Markov models [6] to estimate lifetime costs and quality-adjusted life expectancy because patients with chest pain often experience important events after their initial presentation and evaluation. The strategies considered were 1) no testing and medical therapy as appropriate, 2) exercise electrocardiography with coronary angiography if test results are positive, 3) exercise echocardiography with coronary angiography if test results are positive, 4) exercise SPECT with coronary angiography if test results are positive, and 5) routine coronary angiography without previous noninvasive testing. Several possible courses of action can follow once the initial test is performed. We considered two diagnostic thresholds for each exercise test: positive (indicative of any coronary artery disease) and strongly positive (indicative of triple-vessel or left main coronary artery disease). We also considered two possible postcatheterization strategies: standard (CABG for triple-vessel or left main coronary artery disease, PTCA for single- or double-vessel coronary artery disease if the patient is eligible; otherwise, medical therapy as appropriate) and conservative (CABG for triple-vessel or left main coronary artery disease; otherwise, medical therapy as appropriate). We based the standard postcatheterization strategy primarily on the appropriateness guidelines developed by RAND Corp. (7). The model outputs were quality-adjusted life expectancy and expected lifetime cost. Incremental analyses were performed by rank ordering all 15 competing strategies by increasing effectiveness after eliminating strategies that were more costly and less effective than another strategy (that is, they were ruled out by simple dominance). We then calculated the incremental cost-effectiveness ratio for each strategy (additional cost divided by additional benefit) compared with the next least expensive strategy. If a strategy was less effective and had a higher incremental cost-effectiveness ratio than another strategy, it was ruled out by weak dominance. A weakly dominated strategy was eliminated from the rank-ordered list, and the incremental cost-effectiveness ratios were recalculated. This process of eliminating weakly dominated strategies and recalculating cost-effectiveness ratios continued until no more weakly dominated strategies were left. Costs and life years were discounted at an annual rate of 3%. All analyses were performed by using SMLTREE software, version 2.99 (James Hollenberg, MD, Roslyn, New York). A schematic representation of the decision tree is shown in Figure 1. Figure 1. Decision tree. M Data Sources Number of Diseased Coronary Arteries The result of coronary angiography was quantified as the number of diseased vessels (zero to three) with a separate category for left main coronary artery disease. Underlying coronary artery disease status, stratified by age, sex, and type of chest pain, was based on the prevalence reported by the Coronary Artery Surgery Study (CASS) registry (2) for patients with no history of myocardial infarction. Among patients with typical, atypical, and nonspecific chest pain, the prevalence of any coronary artery disease was 95%, 71%, or 18% in men 50 to 59 years of age and 68%, 30%, or 6% in women in this age range (Figure 2). Figure 2. Prevalence of coronary artery disease. Noninvasive Test Characteristics The sensitivity and specificity of exercise electrocardiography for the detection of any coronary artery disease were obtained from a meta-analysis of 150 studies (3) (Table 1). The sensitivity and specificity of exercise echocardiography and exercise SPECT for the detection of any coronary artery disease were obtained from a recent meta-analysis (8), which yielded similar sensitivities but statistically different specificities (Table 1). The sensitivity for multivessel (double-vessel, triple-vessel, or left main coronary artery) disease was calculated by using the ratio of the sensitivity among patients with multivessel disease relative to that among patients with any coronary artery disease, estimated from studies in which details on the extent of coronary artery disease were reported (17-21). The sensitivities for severe (triple-vessel or left main coronary artery) disease and for left main coronary artery disease were also calculated on the basis of similar ratios. The probability of strongly positive test results by coronary disease category were calculated by using the estimated ratio of the probability of a strongly positive result to the probability of any positive result among each of the coronary artery disease categories (17-20). Some patients undergoing an exercise test were assumed to have an indeterminate result (30% of those undergoing exercise electrocardiography, 10% of those undergoing exercise echocardiography, and 2% of those undergoing exercise SPECT); another noninvasive test was done in these patients. Because data are inadequate on the sensitivity and specificity of each exercise test among a group of patients with indeterminate test results on their first test, we assumed that the overall sensitivity and specificity of the test remained unchanged if it was preceded by another test with indeterminate results and that only the cost of the additional test was incurred. Table 1. Selected Model Variables Short-Term Risks Coronary angiography was associated with an overall 0.1% probability of death and 0.06% probability of nonfatal myocardial infarction. These rates varied depending on extent of coronary anatomy involved (22, 23). In single- and double-vessel coronary artery disease, PTCA was associated with mortality rates of 0.2% and 0.9% and nonfatal myocardial infarction rates of 3.5% and 5.2%, respectively (24). The overall probability of death associated with CABG was 3.2%, and the probability of nonfatal myocardial infarction was 7.0% (25-27). The risk for death of CABG was adjusted to be higher for women and for patients in older age ranges (27). We assumed that 5% of patients treated with PTCA undergo emergent CABG for immediate occlusions (15, 28-30). Long-Term Prognosis Long-term survival was modeled on an intention- to-treat basis in that prognosis was determined only by the initial patient variables (age, sex, extent of coronary artery disease, and treatment) (16, 31-37). Mortality risk ratios for extent of coronary artery disease and mortality risk reductions by CABG (that is, the percentage of coronary artery disease-related mortality reduced by surgery) were derived t