Performance of the traditional age, sex, and angina typicality-based approach for estimating pretest probability of angiographically significant coronary artery disease in patients undergoing coronary computed tomographic angiography: results from the multinational coronary CT angiography evaluation for clinical outcomes: an international multicenter registry (CONFIRM)

Abstract

Background: Guidelines for the management of patients with suspected coronary artery disease (CAD) rely on the age, sex, and angina typicality-based pretest probabilities of angiographically significant CAD derived from invasive coronary angiography (guideline probabilities). Reliability of guideline probabilities has not been investigated in patients referred to noninvasive CAD testing.

Methods and results: We identified 14048 consecutive patients with suspected CAD who underwent coronary computed tomographic angiography. Angina typicality was recorded with the use of accepted criteria. Pretest likelihoods of CAD with ≥ 50 diameter stenosis (CAD50) and ≥ 70 diameter stenosis (CAD70) were calculated from guideline probabilities. Computed tomographic angiography images were evaluated by ≥ 1 expert reader to determine the presence of CAD50 and CAD70. Typical angina was associated with the highest prevalence of CAD50 (40 in men, 19 in women) and CAD70 (27 men, 11 women) compared with other symptom categories (P<0.001 for all). Observed CAD50 and CAD70 prevalences were substantially lower than those predicted by guideline probabilities in the overall population (18 versus 51 for CAD50, 10 versus 42 for CAD70; P<0.001), driven by pronounced differences in patients with atypical angina (15 versus 47 for CAD50, 7 versus 37 for CAD70) and typical angina (29 versus 86 for CAD50, 19 versus 71 for CAD70). Marked overestimation of disease prevalence by guideline probabilities was found at all participating centers and across all sex and age subgroups.

Conclusion: In this multinational study of patients referred for coronary computed tomographic angiography, determination of pretest likelihood of angiographically significant CAD by the invasive angiography-based guideline probabilities greatly overestimates the actual prevalence of disease.

Figure 1

Observed prevalence (black bars) and expected prevalence (spotted bars) of angiographically ≥50% stenotic coronary artery disease (CAD50) in study men (top graph) and women (bottom graph) with no symptoms, nonanginal chest pain, atypical angina, and typical angina. Note that the total sample sizes shown are smaller than those in Table 1 because patients reporting only dyspnea are not included. The 4 collections of bars in each graph are grouped by symptom category and stratified by age decade. Within each symptom group, each black bar should be compared to the spotted bar to its immediate right (asymptomatic patients have no direct comparison). The value above each black bar is the ratio of observed-to-expected CAD50 prevalence. Expected prevalence in patients with atypical angina and typical angina were dramatically higher than observed prevalence, regardless of age. With increasing age, observed-to-expected ratios increased in men with atypical angina (p<0.001) and typical angina (p<0.001) but stayed unchanged in women.

Figure 2

Overall observed prevalence (black bars) of angiographically ≥50% stenotic coronary artery disease (CAD50) was substantially lower than expected prevalence (spotted bars) at every participating center. The observed-to-expected ratios ranged from 0.18 (Site 5) to 0.66 (Site 4), and absolute differences between observed and expected prevalence ranged from 14% to 45%. The 2 sites with the lowest observed-to-expected ratios were Site 5 and Site 9. Site 5 was in South Korea, the only center outside of North America and Europe. Patients at Site 9 were substantially younger than patients at other sites. The 2 sites with the highest observed-to-expected ratios were Site 6 and Site 8 (Site 4 discounted due to very small sample size). Populations at both sites had relatively low rates of atypical angina and relatively high rates of typical angina. Site 8 patients also had the highest rate of patients with high risk factor burden (diabetes or ≥3 non-diabetes risk factors). RF = risk factor.

Figure 3

Observed prevalence (black bars) and expected prevalence (spotted bars) of angiographically ≥70% stenotic coronary artery disease (CAD70) in study men (top graph) and women (bottom graph). Expected prevalence was calculated using the algorithm described by Pryor and colleagues, which incorporates sex, age, angina typicality, history of prior myocardial infarction, presence of Q-waves on resting ECG, and presence of 3 risk factors: diabetes, dyslipidemia, and active smoking. Study patients were assumed to have no Q-waves on resting ECG. Within each symptom category, patients were subgrouped by number of risk factors. The value above each black bar is the ratio of observed-to-expected prevalence. In all groups, expected prevalence was higher than observed prevalence. The differences were particularly dramatic in patients with atypical angina or typical angina and <3 risk factors, where observed-to-expected ratios were <0.4. RF = risk factor.