Prognostic Value of Noninvasive Cardiovascular Testing in Patients with Stable Chest Pain: Insights from the PROMISE Trial
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 Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, patients with stable chest pain and intermediate pre-test probability for obstructive coronary artery disease (CAD) were randomized 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 endpoint was death, myocardial infarction, or unstable angina hospitalizations over a median follow-up of 26.1 months.
Results—Both prevalence of normal test results and incidence rate of events in these patients were significantly lower among 4500 patients randomized to CTA compared to 4602 patients randomized to functional testing (33.4% vs. 78.0%, and 0.9% vs. 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% vs. 12.7%, respectively), with both findings having similar prognostic value (hazard ratio [HR], 3.74 [95% 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, HRs for events as compared to 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] vs. 0.64 [95% CI, 0.59-0.69]; P=0.04). If 2714 patients with at least 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 due to nonobstructive CAD, provides better prognostic information than functional testing in contemporary stable chest pain patients with a low burden of obstructive CAD, myocardial ischemia, and events.
Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01174550
- Received July 5, 2016.
- Revision received March 16, 2017.
- Accepted March 23, 2017.