A post hoc analysis of the PROMISE trial has found that quantitative coronary plaque measures derived from coronary computed tomographic angiography (CCTA) can independently predict major adverse cardiovascular events (MACE) in symptomatic patients without a known history of coronary artery disease (CAD).¹ The findings suggest that total plaque burden and noncalcified plaque burden may enhance risk stratification beyond traditional clinical factors and qualitative CCTA metrics.
Methodology
This analysis was conducted on data from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, a prospective randomised clinical trial conducted across 193 sites in North America.² The cohort included 4,267 symptomatic outpatients without known CAD who were randomised to the CCTA arm of the trial.
Using core laboratory-based analysis, researchers quantified several plaque measures, including total plaque volume (TPV), total plaque burden (TPB), and noncalcified plaque burden (NCPB), which were normalised by vessel volume. The primary endpoint was MACE, a composite of all-cause death, nonfatal myocardial infarction, or hospitalisation for unstable angina, assessed over a median follow-up of 25 months.
Results
The study found that both TPB and NCPB were independent predictors of MACE after adjusting for atherosclerotic cardiovascular disease risk, statin use, coronary artery calcium score, ≥50% stenosis, and high-risk plaque features. For every 10% increase, the adjusted hazard ratio (aHR) for MACE was 1.18 for TPB (95% CI, 1.05–1.34; p=0.006) and 1.20 for NCPB (95% CI, 1.05–1.37; p=0.007).
The researchers also identified optimal predictive cut-offs. Patients with a TPV of ≥87mm³, a TPB of ≥35%, or an NCPB of ≥20% had a nearly two-fold increased risk of MACE. The aHRs were 2.07 (95% CI, 1.24–3.49) for TPV, 1.96 (95% CI, 1.21–3.17) for TPB, and 1.77 (95% CI, 1.12–2.82) for NCPB.
Interpretation
The authors noted that, “In symptomatic patients without known CAD, coronary plaque volumes and burdens are low but are related to CAD risk factors and independently predictive of MACE.”¹ These quantitative measures may offer a more refined approach to risk assessment in patients with early-stage disease, potentially guiding the initiation and intensity of preventive therapies.
Next Steps
The study highlights the potential of quantitative CCTA analysis in early CAD risk stratification. However, the authors concluded that the clinical utility of this approach requires prospective evaluation to confirm these findings and establish its role in routine clinical practice.
This study was funded by the National Heart, Lung, and Blood Institute.
References
1. Karády J, Mayrhofer T, Brendel JM, et al. Prognostic Value of Plaque Volume in Patients With First Diagnosis of Coronary Artery Disease: A Substudy of the PROMISE Randomized Clinical Trial. JAMA Cardiol. 2026. https://doi.org/10.1001/jamacardio.2025.5520
2. Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015;372(14):1291-1300. https://doi.org/10.1056/NEJMoa1415516
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