Aspirin and high-intensity statin strategy for people with very high coronary calcium

an Investigator-initiated, Multicenter, Open-label, 2-by-2 Factorial, and Randomized Trial to Evaluate the Role of Aspirin and High-intensity Statin Therapy, Respectively, in Individuals With Severe Coronary Calcification (Coronary Calcium Score ≥300) to Prevent Atherosclerotic Cardiovascular Disease (ASCVD) Events With Severe Coronary Calcification (CAC ≥300)

This trial will test whether taking aspirin and/or a high‑intensity statin reduces heart attack and stroke risk in people aged 40–70 with very high coronary calcium (CAC ≥300) and at least one cardiovascular risk factor.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 5000 (estimated)
• Ages: 40 Years to 70 Years
• Sex: All
• Sponsor: Asan Medical Center (Academic / other)
• Locations: 1 site (Seoul)
• Trial ID: NCT06676280 on ClinicalTrials.gov

What this trial studies

This Phase 4 interventional trial enrolls adults aged 40–70 with a coronary artery calcium score ≥300 and one or more cardiovascular risk factors, and who do not have prior symptomatic coronary disease or other documented ASCVD. Participants are assigned to aspirin versus no aspirin and to high‑intensity statin therapy versus guideline‑directed statin therapy, with regular follow‑up visits and safety monitoring. The trial will compare atherosclerotic cardiovascular event rates (for example myocardial infarction, stroke, and cardiovascular death) between groups over the follow‑up period. Imaging and clinical assessments will track adherence, cardiovascular outcomes, and potential adverse effects such as bleeding or statin intolerance.

Who should consider this trial

Good fit: Adults 40–70 years old with a coronary artery calcium score ≥300 Agatston units and at least one risk factor (dyslipidemia, diabetes, hypertension, smoking, or family history) who do not have prior symptomatic coronary disease or other documented ASCVD are ideal candidates.

Not a fit: People with prior clinical ASCVD (previous myocardial infarction, acute coronary syndrome, coronary or other arterial revascularization, stroke or TIA, >50% carotid stenosis), symptomatic coronary disease, or heart failure are excluded and unlikely to gain from this primary‑prevention approach.

Why it matters

Potential benefit: If successful, this approach could reduce heart attacks and strokes by preventing ASCVD events in people with very high coronary calcium.

How similar studies have performed: Prior trials show clear benefit of statins and that coronary calcium helps identify higher‑risk individuals, while aspirin in primary prevention has shown mixed results, so testing these strategies together in patients with CAC ≥300 is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. The subject must be aged between 40 and 70 years.
2. Patients who have coronary artery calcium score ≥300 Agatston Unit on coronary calcium computed tomography.
3. Patients who have 1 or more CVD risk factors in below;

   * dyslipidemia or,
   * diabetes or,
   * hypertension or,
   * family history of CVD or,
   * smoking
4. Patients agree to the study protocol and the schedule of clinical follow-up, and provides informed, written consent, as approved by the appropriate Institutional Review Board/Ethical Committee of the respective clinical site.

Exclusion Criteria:

1. Individuals who have symptomatic coronary artery disease or heart failure.
2. Patients who have documented clinical Atherosclerotic Cardiovascular Disease: previous myocardial infarction, acute coronary syndrome, stable angina, coronary revascularization and other arterial revascularization procedures, stroke and Transient ischaemic attack (TIA), \>50% carotid stenosis or previous carotid endarterectomy or stenting, aortic aneurysm and peripheral artery disease.
3. Patients who have evidence of myocardial ischemia on non-invasive stress test including stress single photon emission CT myocardial perfusion imaging (SPECT MPI), cardiovascular magnetic resonance (CMR) imaging, stress echocardiography, or treadmill test, or on invasive stress test including Fractional flow reserve (FFR) \< 0.80 on invasive coronary angiography (diameter stenosis\>50% without objective evidence of ischemia could be enrolled).
4. Patients at high risk of bleeding: gastrointestinal hemorrhage or peptic ulcer within the previous 6 months; active hepatic disease such as cirrhosis or active hepatitis; use of warfarin, or other anticoagulant therapy; or has a history of aspirin allergy.
5. Patients with atrial fibrillation and flutter.
6. Patients with severe left ventricular dysfunction (ejection fraction ≤30%) or severe valvular heart disease who experience dyspnea on exertion (The NYHA (New York Heart Association) Functional Classification III-IV).
7. History of allergy or severe adverse reaction to aspirin or statin or ezetimibe.
8. History of myositis or myopathy with active disease in the 180 days prior to study entry.
9. Patients with active liver disease or persistent unexplained serum transaminase elevation.
10. Patients who have significantly abnormal findings which identified violation for safety by investigator on physical examination, blood test and electrocardiogram.
11. History of alcohol or drug abuse.
12. Concurrent medical condition with a life expectancy of less than 1 years.
13. Pregnant and/or lactating women.
14. Patient was unable to provide written informed consent or participate in log-term follow up.

Where this trial is running

Seoul

• Asan Medical Center — Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: Jung-min Ahn, MD

Conditions Cardiovascular Diseases; atherosclerotic cardiovascular disease; aspirin; high-intensity statin