wCAR-Austria: A Women-Specific Score to Assess Cardiovascular Risk in Women Aged 40 to 65

Area Under the ROC Curve (AUC) of the wCAR Score for Detecting Any Coronary Plaque on Photon-Counting CCTA in Women With Intermediate wCAR Risk (6-10 Points)

Discriminative performance of the women's cardiovascular risk (wCAR) total score for the presence of any coronary plaque (calcified, mixed or non-calcified) on photon-counting coronary computed tomography angiography (CCTA), with central core-lab image evaluation blinded to the wCAR score. Analysis population: study-mandated CCTA participants randomly sampled from the intermediate wCAR stratum (6-10 points, n=100). Reported as AUC with 95% confidence interval (ROC analysis, DeLong method; bootstrap confidence intervals). Co-primary with E1b; multiplicity controlled by Bonferroni-Holm closed testing. Protocol endpoint E1a.

Time to First Major Adverse Cardiovascular Event (MACE: Cardiovascular Death, Non-Fatal Myocardial Infarction, Non-Fatal Stroke or Coronary Revascularisation) by wCAR Risk Category

Prognostic value of the wCAR score for MACE in the total cohort (n=800). MACE is defined as the first occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or coronary revascularisation, adjudicated by an independent endpoint committee blinded to participant identity using pseudonymised clinical records. Reported as hazard ratio with 95% CI for wCAR categories R3/R4 versus R1/R2 (Cox proportional hazards regression) and Harrell's C-statistic; Kaplan-Meier estimates by wCAR risk category. Protocol endpoint Phase B.

Percentage of Participants Achieving the Composite Risk-Factor Endpoint at Month 24 (wCAR Class Improvement or Reduction in LDL-C, Systolic Blood Pressure, TyG Index or HbA1c)

Binary composite endpoint, achieved if at least one of the following criteria is met at month 24 compared with baseline: (a) improvement by at least one wCAR risk class (e.g., very high to high); (b) LDL-C reduction of at least 15%; (c) systolic blood pressure reduction of at least 10 mmHg; (d) TyG index reduction of at least 10%; (e) HbA1c reduction of at least 0.3 percentage points (participants with prediabetes or type 2 diabetes only). Population: participants with wCAR score of 11 points or higher randomised 1:1 to Arm A (wCAR-guided precision prevention) or Arm B (guideline-based standard care). Endpoint assessment blinded to arm allocation (PROBE design). Reported as number and percentage of participants achieving the endpoint per arm; primary analysis by intention-to-treat using logistic regression adjusted for centre and wCAR stratum (risk difference and odds ratio with 95% CI). Protocol endpoint E2 (wCAR-CARE substudy).

Area Under the ROC Curve (AUC) of the wCAR Score for Detecting Any Coronary Plaque on Photon-Counting CCTA in Women With Intermediate or High wCAR Risk (6-15 Points)

Discriminative performance of the women's cardiovascular risk (wCAR) total score for the presence of any coronary plaque (calcified, mixed or non-calcified) on photon-counting coronary computed tomography angiography (CCTA), with central core-lab image evaluation blinded to the wCAR score. Analysis population: study-mandated CCTA participants randomly sampled from the intermediate (6-10 points, n=100) and high (11-15 points, n=100) wCAR strata (combined n=200). Reported as AUC with 95% confidence interval (ROC analysis, DeLong method; bootstrap confidence intervals). Co-primary with E1a; multiplicity controlled by Bonferroni-Holm closed testing. Protocol endpoint E1b.