In a post hoc analysis of a prospective randomized clinical trial conducted at 193 North American sites, investigators examined whether quantitative coronary computed tomographic angiography (CCTA) plaque measures provide incremental prognostic value in symptomatic outpatients without known coronary artery disease (CAD). The parent trial enrolled participants from July 27, 2010, to October 31, 2014; this analysis was conducted between January 2021 and July 2024. The analysis was published in the JAMA Cardiology.

Among 4267 patients (mean [SD] age 60.4 [8.2] years; 51.5% female), median total plaque volume (TPV) was 39.8 mm³ (IQR 0–167). Higher TPV (≥median) was associated with older age, male sex (60.3% vs 36.6%), and higher median atherosclerotic cardiovascular disease risk scores (14.4 vs 7.9). Total plaque burden (TPB) and noncalcified plaque burden (NCPB) independently predicted major adverse cardiovascular events (MACE) after adjustment for clinical risk factors, statin use, and qualitative CCTA findings (TPB: adjusted HR 1.18; 95% CI 1.05–1.34; P=.006; NCPB: adjusted HR 1.20; 95% CI 1.05–1.37; P=.007).

Optimal cut points, i.e., TPV ≥87 mm³, TPB ≥35%, and NCPB ≥20%, were each associated with nearly twofold increased MACE risk (TPV: adjusted HR 2.07; 95% CI 1.24–3.49; TPB: 1.96; 95% CI 1.21–3.17; NCPB: 1.77; 95% CI 1.12–2.82).
Limitations include vendor-specific quantification, lack of standardized reporting, median 25-month follow-up, exclusion of eGFR from models, and exploratory analysis without multiple-testing adjustment.

In symptomatic patients without known CAD, higher quantitative plaque burdens were independently associated with MACE. Prospective validation is required before clinical implementation of quantitative CCTA-based risk estimation.