Age-Related Differences in the Noninvasive Evaluation for Possible Coronary Artery Disease: Insights From the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial

Key PointsQuestionAmong patients in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, did age affect the likelihood of a positive test result for coronary artery disease and its prognostic value, and did this differ according to type of test (anatomic vs functional test)? FindingsIn this prespecified PROMISE trial substudy, test result positivity increased with age regardless of the noninvasive test completed. However, among patients younger than 65 years, anatomic testing provided better prognostic discrimination, whereas among patients 65 years and older, functional testing was able to distinguish future risk, with a significant interaction between age, test type, and prognosis. MeaningPositive functional test results vs anatomic test results differ in their association with cardiovascular death or myocardial infarction across patient age. Age-specific approaches to the noninvasive evaluation of coronary artery disease should be further explored. ImportanceAlthough cardiovascular (CV) disease represents the leading cause of morbidity and mortality that increases with age, the best noninvasive test to identify older patients at risk for CV events remains unknown. ObjectiveTo determine whether the prognostic utility of anatomic vs functional testing varies based on patient age. Design, Setting, and ParticipantsPrespecified analysis of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) study, which used a pragmatic comparative effectiveness design. Participants were enrolled from 193 sites across North America and comprised outpatients without known coronary artery disease (CAD) but with symptoms suggestive of CAD. Data were analyzed between October 2018 and April 2019. InterventionsRandomization to noninvasive testing with coronary computed tomographic angiography or functional testing. Main Outcomes and MeasuresThe composite of CV death/myocardial infarction (MI) over a median follow-up of 25 months. ResultsAmong 10003 PROMISE patients, we included the 8966 who received the noninvasive test to which they were randomized and had interpretable results; 6378 (71.1%) were younger than 65 years, 2062 (23.0%) were between ages 65 and 74 years, and 526 (5.9%) were 75 years and older. More than half of participants were women (4720 of 8966 [52.6%]). Only a minority of patients were of nonwhite race/ethnicity, a proportion that was lower among the older age groups (1071 of 6378 [16.8%] for <65 years; 258 of 2062 [12.5%] for age 65-74 years; 41 of 526 [7.8%] for >= 75 years). Compared with patients younger than 65 years, older patients were more likely to have a positive test result (age 65-74 years: odds ratio, 1.65; 95% CI, 1.42-1.91; age >= 75 years: odds ratio, 2.32; 95% CI, 1.83-2.95), regardless of noninvasive test completed. A positive functional test result was not associated with CV death/MI in patients younger than 65 years (hazard ratio [HR], 1.09; 95% CI, 0.43-2.82) but it was among older patients (age 65-74 years: HR, 3.18; 95% CI, 1.44-7.01; age >= 75 years: HR, 6.55; 95% CI, 1.46-29.35). Conversely, a positive anatomic test result was associated with CV death/MI among patients younger than 65 years (HR, 3.04; 95% CI, 1.46-6.34) but not among older patients (age, 65-74 years: HR, 0.67; 95% CI, 0.15-2.94; age >= 75 years: HR, 1.07; 95% CI, 0.22-5.34; P for interaction=.01). An elevated coronary artery calcium score was predictive of events in patients younger than 65 years (HR, 2.73; 95% CI, 1.31-5.69) but not for older patients (age 65-74 years: HR, 0.44; 95% CI, 0.14-1.42; age >= 75 years: HR, 1.31; 95% CI, 0.25-6.88). Conclusions and RelevanceOlder patients with stable symptoms suggestive of CAD are more likely to have a positive noninvasive test result and more coronary artery calcium. However, only a positive functional test result was associated with risk of CV death/MI. Age-specific approaches to noninvasive evaluation of CAD should be further examined. Trial RegistrationClinicalTrials.gov identifier: NCT01174550 This prespecified analysis of the PROMISE randomized clinical trial determines whether the prognostic utility of anatomic vs functional testing for coronary artery disease varies based on patient age. (c) 2019 American Medical Association. All rights reserved.