Association of high-risk CT coronary artery plaque features with major adverse cardiovascular events: a prespecified secondary analysis of the DISCHARGE trial

Objectives: The prognostic role of high-risk plaque (HRP) features, including high coronary calcium scores detected by CT, beyond traditional cardiovascular risk factors and obstructive coronary artery disease (CAD), remains uncertain. This study evaluated the prognostic value of a combined HRP definition in stable chest pain patients with low-to-intermediate pretest probability of CAD. Materials and methods: This prespecified analysis included participants randomized to the CT arm of the pragmatic, prospective 26-center European DISCHARGE trial (NCT02400229). The primary endpoint was major adverse cardiovascular events (MACE: cardiovascular death, nonfatal myocardial infarction, or stroke); the secondary endpoint was expanded MACE (transient ischemic attack and major procedure-related complications). Our combined HRP definition was any coronary plaque with positive remodeling, napkin-ring sign, low attenuation, or total calcium score ≥ 400 Agatston units. Results: Among 1745 participants (age: 60 ± 10 years, 990 female), 35 MACE and 47 expanded MACE occurred at a median follow-up of 3.5 years (IQR: 2.9–4.2). After risk factor adjustment, the combined HRP definition was associated with a higher risk of MACE (HR: 3.81; 95% CI: 1.01–14.6; p = 0.050) and remained significantly associated with expanded MACE (HR: 0.21; 95% CI: 1.07–9.66; p = 0.038). Patients with both HRP and obstructive CAD conferred the highest MACE (HR: 8.78; 95% CI: 2.90–26.6; p < 0.001) and expanded MACE risk (HR: 7.31; 95% CI: 3.06–17.48; p < 0.001) compared with patients without HRP or obstructive CAD. HRP alone showed a prognostic impact comparable to obstructive CAD alone. Conclusion: HRP features on coronary CT provide incremental predictive value for MACE, comparable to obstructive CAD, after adjusting for traditional cardiovascular risk factors in this large pan-European cohort. Trial registration: ClinicalTrials.gov NCT02400229. Key Points: Question Do high-risk plaque (HRP) features on coronary CT have incremental prognostic value after adjustment for cardiovascular risk factors in stable chest pain? Findings A combined definition of HRP features on coronary CT was independently associated with major adverse cardiovascular events, with similar prognostic value to obstructive coronary artery disease after risk adjustment. Clinical relevance HRP features, including a coronary artery calcium score ≥ 400 Agatston units or traditional high-risk plaque characteristics on coronary CT, provide incremental prognostic value in predicting MACE in stable chest pain patients, offering a potential tool for improved risk stratification and management.