Survival After Initial Stress Testing vs Anatomic Testing in Suspected Coronary Artery Disease

Importance Symptoms suggestive of coronary artery disease (CAD) often require noninvasive testing for diagnostic and prognostic evaluation. Objective To determine long-term outcomes in patients randomized to functional (stress) vs anatomic (coronary computed tomographic angiography [CTA]) initial testing. Design, Setting, and Participants This study is a 2025 follow-up analysis of mortality of participants in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) randomized clinical trial, which was conducted from 2009 to 2014, using a 2024 National Death Index search. Median (IQR) follow-up duration was 10.6 (9.9-11.3) years; maximum follow-up was 12.4 years. PROMISE was conducted at 193 multispecialty outpatient sites in North America among 10 003 symptomatic patients requiring testing for suspected CAD. Data analysis was conducted from August 2024 to March 2025. Intervention Participants were randomized 1:1 to initial CTA or stress testing. Testing and subsequent care were performed by sites according to usual practices. Main Outcomes and Measures The PROMISE trial’s original primary end point was death, myocardial infarction, unstable angina hospitalization, or major procedural complication. The primary end point for extended follow-up was all-cause death, with cardiovascular (CV) death as a secondary end point. Results At enrollment, mean (SD) participant age was 61 (8) years, 5270 participants (52.7%) were women, and 8762 (87.6%) had chest pain or dyspnea. Death occurred in 1128 participants (14.4%), including 558 (14.3%) in the CTA arm and 570 (14.5%) in the stress arm (unadjusted hazard ratio [HR], 0.98; 95% CI, 0.87-1.10). There was no demonstrable difference in cardiovascular mortality, although the point estimate favored CTA (HR, 0.84; 95% CI, 0.67-1.05; adjusted HR, 0.89; 95% CI, 0.41-1.94). There were no significant interactions between all-cause death or CV death and study arm by age (<60 or ≥60 years) ( P value for interaction = .19), gender ( P value for interaction = .60), or race and ethnicity ( P value for interaction = .47). A CTA indicating any degree of abnormality, including mild (nonobstructive CAD), moderate, and severe findings, conferred elevated adjusted HRs of death (1.99-3.44; all P < .001) compared to normal study results. Among stress testing results, only a severe abnormality was prognostically significant (HR, 1.45; 95% CI, 1.10-1.91). In landmark analyses of those alive at 90 days, there were no interactions between randomized testing and use of statins ( P value for interaction = .22), β-blockers ( P value for interaction = .76), or antiplatelet agents ( P value for interaction = .49). Conclusions and Relevance In long-term follow-up of the PROMISE randomized clinical trial, initial noninvasive test selection in patients with stable symptoms of suspected CAD did not affect all-cause or CV mortality at 10 years. Trial Registration ClinicalTrials.gov Identifier: NCT01174550