Statin plus ezetimibe without aspirin versus statin with aspirin for people with high coronary calcium

Comparison of Intensive Lipid-Lowering Therapy With a Statin-Ezetimibe Combination (Without Aspirin) vs. Statin Monotherapy (With Aspirin) In Asymptomatic Patient With Coronary Artery Calcification

This study tests whether using a stronger cholesterol regimen (statin plus ezetimibe) without aspirin works as well as a standard statin with aspirin to prevent heart problems in adults who have high coronary artery calcium.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 7435 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Asan Medical Center (Academic / other)
• Locations: 1 site (Seoul)
• Trial ID: NCT06722521 on ClinicalTrials.gov

What this trial studies

This randomized Phase 4 trial enrolls asymptomatic adults with significant coronary artery calcification (Agatston score ≥100) and no physiologically significant coronary artery disease to compare two prevention strategies. One group receives pitavastatin 4 mg plus ezetimibe 10 mg daily without aspirin, and the other receives pitavastatin 2 mg plus aspirin 100 mg daily. The study measures cardiovascular events and safety outcomes, including bleeding, over follow-up to determine if the intensive lipid-lowering approach without aspirin is non-inferior to the statin-plus-aspirin strategy. The design aims to balance efficacy in preventing events against the harms of routine aspirin use in primary prevention.

Who should consider this trial

Good fit: Asymptomatic adults aged 19 or older with an Agatston coronary artery calcium score ≥100, no physiologically significant coronary disease, and the ability to attend study visits are ideal candidates.

Not a fit: People with prior major atherosclerotic cardiovascular disease events (such as MI, coronary revascularization, ischemic stroke) or those with symptomatic peripheral artery disease or other indications that require aspirin are unlikely to benefit from this enrollment.

Why it matters

Potential benefit: If successful, patients with high coronary calcification might avoid routine aspirin and its bleeding risk while maintaining similar protection against cardiovascular events through more intensive cholesterol lowering.

How similar studies have performed: Previous large trials have questioned routine aspirin for primary prevention due to bleeding risk while trials adding ezetimibe to statins (e.g., IMPROVE-IT) have shown event reduction in higher-risk patients, but a head-to-head comparison in asymptomatic high-CAC patients is novel.

Eligibility criteria

Inclusion Criteria

1. Adults aged 19 years and older
2. Asymptomatic patients with significant coronary calcification (Agatston score ≥ 100) and no physiologically significant coronary artery disease (CAD)

   * The coronary CT scan used to establish the CAC score must be performed within 3 years prior to randomization.
   * The assessment of physiological significance must be performed within 6 months prior to randomization
3. Participants will be eligible for inclusion regardless of prior statin or anti-platelet agents use.

Exclusion Criteria

1. Major ASCVD events (clinically documented ASCVD)

   If at least one of the following criteria is present via patient history, physical examination, or medical records at the time of screening, the patient is not eligible:
   * Acute coronary syndrome (MI or unstable angina)
   * Coronary revascularization (PCI, CABG) or other arterial revascularization
   * Ischemic stroke (Not TIA)
   * Symptomatic peripheral arterial disease (history of claudication with ABI \<0.90, or previous revascularization or amputation
2. Patients with physiologically significant CAD

   * Moderate to severe CAD (diameter stenosis \>50%) on CCTA with positive strest test (thallium, treadmil, stress echocardiography)
   * Moderate to severe CAD (diameter stenosis \>50%) on CAG with positive fractional flow reserve (FFR) \< 0.8
3. Patients with familial hypercholesterolemia.
4. Patients with low-density lipoproteins cholesterol (LDL-C) ≥ 190 mg/dL regardless taking a statin or not.
5. Continuation of PCSK9 inhibitor is required during the clinical trial
6. Patients with chronic kidney disease (\<eGFR 30mL/min/1.73m2)
7. Advanced liver disease (Child-Pugh B or C)
8. Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST \> 5 times upper limit of normal).
9. History of gastrointestinal bleeding, peptic ulcer, or intracranial hemorrhage within 6 months prior screening
10. Patients with a history of organ transplantation who are on immunosuppressive therapy
11. Concurrent use of other medications that may increase bleeding risk such NOAC and warfarin
12. A history of significant allergic reaction to aspirin or statin/ezetimibe
13. A diagnosis of cancer (other than superficial squamous or basal cell skin cancer) in the past 3 years or current treatment for the active cancer.
14. Life expectancy \< 1 years for any non-cardiac or cardiac causes.
15. Patient's pregnant or breast-feeding or child-bearing potential.
16. Any clinically significant abnormality identified at the screening visit, physical examination, laboratory tests, or electrocardiogram which, in the judgment of the Investigator, would preclude safe completion of the study.
17. Unwillingness or inability to comply with the procedures described in this protocol

Where this trial is running

Seoul

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

Study contacts

• Study coordinator: Seung-Whan Lee

Conditions Primary Prevention; Vascular Calcification; Cardiovascular Diseases; Aspirin; Statin