Results from the PROMISE trial showed that the presence and extent of coronary artery disease detected by CT angiography better predicted the risk of future cardiac events than did measures of exercise tolerance or restricted blood flow to the heart muscle.
An analysis of diagnostic test results from the Prospective Multicentre Imaging Study for Evaluation of Chest Pain (PROMISE) trial – in which patients with stable chest pain were randomized to either anatomic or functional testing as an initial diagnostic strategy – showed that the presence and extent of coronary artery disease detected by CT angiography better predicted the risk of future cardiac events than did measures of exercise tolerance or restricted blood flow to the heart muscle.
The superiority of CT angiography primarily depended on its ability to reveal non-obstructive coronary artery disease. The report was by a team led by Dr Udo Hoffmann, of the Massachusetts General Hospital (MGH).
“We do show that obstructive coronary artery disease and myocardial ischemia remain the strongest predictors of future cardiovascular events, but for the first time, in a randomised comparison we demonstrate the ability of CT angiography (CTA) to identify a large group of at-risk patients who would have been missed by functional stress testing,” says Hoffmann, who is director of the MGH Cardiac MR PET CT Programme.
“This not only provides important information for physicians making choices regarding which test to perform but also suggests that implementing lifestyle changes and potentially the use of statin drugs may lower the risk of future clinical events for patients with non-obstructive disease.”
The PROMISE trial was conducted at 193 centres across North America to determine whether a care strategy starting with coronary CTA, which reveals the structure of blood vessels supplying the heart, or a strategy starting with functional testing, measures such as stress testing or echocardiography that reflect how well the heart muscle is working, provided better guidance for clinical decisions regarding patients with chest pain. Those results found similar outcomes for both strategies in terms of the incidence of future cardiovascular events.
The current study directly analysed associations between the results of all diagnostic tests and the risk of future cardiac events in around 9,100 of the more than 10,000 patients in the PROMISE trial. The most important result indicated that the ability of coronary CTA to identify non-obstructive coronary artery disease – a less-than-70% narrowing of a coronary artery – identifies an at-risk group of patients not found by functional testing. In fact, most of the cardiovascular events during the study’s two-year follow-up period occurred in patients not initially diagnosed with coronary artery obstruction.
While functional testing on its own was inferior to CTA, combining the results of functional testing with traditional cardiovascular risk factors – such as cholesterol levels, blood pressure and smoking status – significantly improved its prognostic value.
“While these observational data cannot prove that treating patients based on the results of CTA testing will automatically result in better health outcomes, they do provide new information enabling a more informed choice of testing for patients with stable chest pain, especially for predicting future cardiovascular risk.” says Hoffmann, who is a professor of padiology at Harvard Medical School. “Future studies also need to determine whether more detailed analysis of exercise parameters in functional testing could improve its prognostic ability; but it’s reassuring that both strategies can provide important prognostic information for patients and their physicians.”
Background: Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing.
Methods: In the PROMISE trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain), patients with stable chest pain and intermediate pretest probability for obstructive coronary artery disease (CAD) were randomly assigned to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA). Site-based diagnostic test reports were classified as normal or mildly, moderately, or severely abnormal. The primary end point was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 26.1 months.
Results: Both the prevalence of normal test results and incidence rate of events in these patients were significantly lower among 4500 patients randomly assigned to CTA in comparison with 4602 patients randomly assigned to functional testing (33.4% versus 78.0%, and 0.9% versus 2.1%, respectively; both P<0.001). In CTA, 54.0% of events (n=74/137) occurred in patients with nonobstructive CAD (1%–69% stenosis). Prevalence of obstructive CAD and myocardial ischemia was low (11.9% versus 12.7%, respectively), with both findings having similar prognostic value (hazard ratio, 3.74; 95% confidence interval [CI], 2.60–5.39; and 3.47; 95% CI, 2.42–4.99). When test findings were stratified as mildly, moderately, or severely abnormal, hazard ratios for events in comparison with normal tests increased proportionally for CTA (2.94, 7.67, 10.13; all P<0.001) but not for corresponding functional testing categories (0.94 [P=0.87], 2.65 [P=0.001], 3.88 [P<0.001]). The discriminatory ability of CTA in predicting events was significantly better than functional testing (c-index, 0.72; 95% CI, 0.68–0.76 versus 0.64; 95% CI, 0.59–0.69; P=0.04). If 2714 patients with at least an intermediate Framingham Risk Score (>10%) who had a normal functional test were reclassified as being mildly abnormal, the discriminatory capacity improved to 0.69 (95% CI, 0.64–0.74).
Conclusions: Coronary CTA, by identifying patients at risk because of nonobstructive CAD, provides better prognostic information than functional testing in contemporary patients who have stable chest pain with a low burden of obstructive CAD, myocardial ischemia, and events.
Udo Hoffmann, Maros Ferencik, James E Udelson, Michael H Picard, Quynh A Truong, Manesh R Patel, Megan Huang, Michael Pencina, Daniel B Mark, John F Heitner, Christopher B Fordyce, Patricia A Pellikka, Jean-Claude Tardif, Matthew Budoff, George Nahhas, Benjamin Chow, Andrzej S Kosinski, Kerry L Lee, Pamela S Douglas