Design and rationale of the WARRIOR ancillary study for coronary CT angiographic analysis

Background Over 50% of women evaluated for suspected ischemia have no obstructive coronary artery disease (INOCA). Statins, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are effective in intermediate outcome trials; however, impact on coronary plaque has not been well characterized. Objectives The Women’s IschemiA TRial to Reduce Events In Non-ObstRuctive CAD (WARRIOR NCT03417388) trial testing intensive medical therapy (IMT) (high intensity statin, ACEI or ARB and low dose aspirin) vs usual care (UC) in women with suspected INOCA offers the opportunity to evaluate the impact of IMT vs UC on plaque composition, and chest pain symptoms by coronary CT angiography (CCTA). We hypothesize that IMT provides beneficial data on plaque composition impacting flow reserve and trial outcomes. Methods This WARRIOR ancillary study will consecutively enroll 200 eligible participants randomized to IMT vs UC by baseline and exit CCTA. Changes in plaque and peri‑coronary artery adipose tissue attenuation (PCAT) characteristics will be quantified. Results Results will address: (1) Changes in coronary plaque characteristics and their hemodynamic significance using AI-enabled quantification of CCTA; (2) Changes in plaque inflammatory characteristics through pericoronary adipose tissue (PCAT) density analysis; (3) Plaque burden, composition and PCAT density changes related to angina score (Seattle Angina Questionnaire [SAQ]), (4) Derive a quantitative machine learning risk score (MLRS) using CCTA-derived variables for prediction of change in angina. Conclusions The ancillary study will be the first to quantify the impact of IMT vs UC on plaque composition, and outcomes in women with suspected INOCA.