CAPRA-EVO: a Randomized Serial PCCT Trial of Early Evolocumab After ACS

• Evolocumab (Drug): Evolocumab will be administered early after randomization in participants assigned to the experimental arm, in addition to standard-of-care lipid-lowering therapy. The treatment is intended to achieve intensive low-density lipoprotein cholesterol reduction and to evaluate its effect on coronary plaque progression or stabilization over 52 weeks.
• Serial photon-counting coronary computed tomography angiography (Diagnostic test): All participants will undergo photon-counting coronary computed tomography angiography at baseline and at 52 weeks. Imaging will be used to assess changes in total atherosclerotic volume, stenosis severity, and high-risk plaque features in non-culprit coronary vessels.
• Standard Lipid-Lowering Therapy (Drug): Participants will receive guideline-directed standard lipid-lowering therapy according to contemporary clinical practice and investigator judgment.

Primary outcomes

• Total atherosclerotic volume and stenosis severity [From enrollment to the end of treatment at 52 weeks]: a. Total atherosclerotic volume (TAV) at the whole-non-culprit-vessel level: Change from baseline CTA (week 0) to endpoint CTA(week 52).
• b. Stenosis severity at the target lesion level (defined as luminal stenosis ≥50%, particularly in left main coronary artery [LMCA] or proximal left anterior descending artery [LAD] OR presence of ≥2 high-risk plaque features) [From enrollment to the end of treatment at 52 weeks]

Secondary outcomes

• HRP change [From enrollment to the end of treatment at 52 weeks]: Change in high-risk plaque (HRP) features from baseline CTA (week 0) to endpoint CTA (week 52).

Sex: All, ages: 40 Years to 75 Years

Inclusion Criteria:

Eligible patients must meet the following criteria:

* Age between 40 and 75 years.
* Diagnosis of ACS, including ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) or unstable angina (UA).
* Successful PCI treatment, with post-procedural TIMI grade 3 flow and residual stenosis <30% and atherosclerotic plaque presence in non-culprit coronary vessels (not attributed to this target event).
* Suboptimal LDL-C control: Patients must have received any statin treatment for at least 4 weeks, with an LDL-C level ≥1.8 mmol/L; or Statin-naive patients must have an LDL-C level ≥3.2 mmol/L.
* Agreement to complete baseline CCTA and laboratory tests within 7 days of enrollment and signed informed consent.
* Commitment to complete 52 weeks of follow-up.

Exclusion Criteria:

* History of coronary artery bypass grafting (CABG).
* History of valve surgery.
* History of PCI treatment before the index ACS event
* Complex bifurcation lesions (Medina 1,1,1).
* Use of PCSK9 inhibitors (e.g., evolocumab, alirocumab) or potent CYP3A4 inhibitors (e.g., itraconazole) within the last 12 months.
* Known intolerance to statins, evolocumab, or other investigational drugs related to the study.
* Hepatic or renal insufficiency (eGFR <60 mL/min/1.73m² or ALT/AST >3 times the upper limit of normal).
* Active autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus).
* Uncontrolled heart failure (NYHA class III-IV) or malignant arrhythmias.
* Known allergy or hypersensitivity to iodinated contrast media
* Hyperthyroidism or active thyroid disease
* Pregnancy or breastfeeding (or plans for pregnancy within the next year).
* Life expectancy of less than 1 year (e.g., due to advanced malignancy).
* Participation in another interventional clinical trial within the past 3 months.

• Yong He, Study director, West China Hospital