The PREVENT-2 trial is to determine whether an initial invasive strategy-consisting of early coronary angiography (CAG) with intent for preventive percutaneous coronary intervention (PCI) in addition to optimal medical therapy (OMT)-reduces the incidence of the primary composite outcome of cardiac death, target-vessel myocardial infarction (MI), unplanned urgent revascularization, or hospitalization for unstable or progressive angina at 3 years, compared with an initial conservative strategy of optimal medical therapy (OMT) alone, in patients with high-risk vulnerable plaque identified by coronary computed tomography angiography (CCTA).

Inclusion Criteria:

1. Patients aged ≥18 years

2. Patients with suspected coronary artery disease (CAD) (e.g., chest pain syndrome or equivalent symptoms) who are evaluated with coronary computed tomography angiography (CCTA)

3. Coronary computed tomography angiography (CCTA) showing:

   Plaque with at least moderate stenosis in one or more major epicardial coronary arteries; and

   At least two high-risk plaque (HRP) feature at the site of stenotic lesions, defined as any of the following:

   • Low-attenuation plaque (LAP) (<70 Hounsfield units)
   • Positive remodeling (PR) (remodeling index >1.2)
   • Napkin-ring sign (NRS)
   • Spotty calcification (SC) (<3 mm in length)

4. Willing and able to provide written informed consent

Exclusion Criteria:

1. Acute coronary syndrome (ACS) requiring urgent or emergent invasive evaluation

2. Hemodynamically unstable conditions

3. Significant left main coronary artery disease (≥50% diameter stenosis)

4. Coronary anatomy unsuitable for either percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)

5. Left ventricular ejection fraction (LVEF) <35%

   → Left ventricular ejection fraction <35%

6. New York Heart Association (NYHA) class III or IV heart failure at entry or hospitalization for exacerbation of chronic heart failure within the previous 6 months

7. Prior coronary artery bypass grafting (CABG)

8. Severe renal dysfunction (estimated glomerular filtration rate <30 mL/min/1.73 m²) or end-stage renal disease on dialysis

9. Contraindication to undergoing coronary computed tomography angiography (CTA) (e.g., allergy to radiographic contrast that cannot be adequately premedicated, any prior anaphylaxis to radiographic contrast, or inability to cooperate with scan acquisition)

10. Contraindications to or planned discontinuation of dual antiplatelet therapy within 1 year

11. Life expectancy less than the duration of the trial due to non-cardiovascular comorbidity

12. Planned cardiac or major noncardiac surgery within the study period

13. Women who are breastfeeding, pregnant, or planning to become pregnant during the course of the study

14. Inability to comply with the study protocol

15. Active participation in another interventional clinical trial involving an unapproved investigational drug or device