GUIDE-CAC: Statin-Ezetimibe Without Aspirin vs. Statin Monotherapy With Aspirin in High Coronary Calcification

NCT ID: NCT06722521

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 7435 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-09
• Study Completion Date: 2032-10-31

Brief Summary

A Multicenter, randomized trial comparing the efficacy and safety of intensive lipid-lowering therapy using a statin-ezetimibe combination without aspirin versus statin monotherapy with aspirin in asymptomatic patients with coronary artery calcification

Detailed Description

Coronary artery calcification is a well-established marker of subclinical atherosclerosis that effectively identifies high-risk individuals for cardiovascular events, even in asymptomatic patients. However, the optimal intensity of preventive interventions-particularly regarding the balance between efficacy and safety-remains unclear in asymptomatic patients with significant coronary calcification.

While aspirin has traditionally been used for the primary prevention of cardiovascular events, recent evidence suggests that its routine use in asymptomatic individuals may carry greater bleeding risks than cardiovascular benefits. In contrast, intensive lipid-lowering therapy with statins and ezetimibe has proven effective in reducing LDL-C levels and preventing cardiovascular events by slowing atherosclerotic progression and stabilizing plaques.

This study aims to evaluate whether intensive lipid-lowering therapy using a statin-ezetimibe combination (without aspirin) is non-inferior to statin monotherapy (with aspirin) in reducing cardiovascular events among patients with significant coronary artery calcification. By comparing these two strategies, we seek to establish whether more aggressive lipid management might obviate the need for aspirin in these intermediate- to high-risk yet asymptomatic patients.

Conditions

Primary Prevention; Vascular Calcification

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intensive lipid-lowering therapy without aspirin

In this group, intensive lipid-lowering therapy is performed without aspirin using pitavastatin 4 mg/ezetimibe 10 mg, targeting patients with coronary artery calcification (Agatston score ≥100) who require primary prevention and do not have physiologically significant coronary artery disease.

◦ Intervention Medications: Pitavastatin 4 mg/ezetimibe 10 mg (aspirin excluded)

Group Type: EXPERIMENTAL

Pitavastatin 4mg and ezetimibe 10mg, taken once daily

Intervention Type: DRUG

Intensive lipid-lowering therapy without aspirin

Statin Monotherapy with Aspirin

IIn this group, moderate-intensity lipid-lowering therapy is administered using pitavastatin 2 mg and aspirin for patients with coronary artery calcification (Agatston score ≥100) who require primary prevention and do not have physiologically significant coronary artery disease.

◦ Intervention Medications: Pitavastatin 2 mg and aspirin (Based on the clinician's judgment, the statin dosage may be increased to pitavastatin 4 mg depending on the LDL response, and if there are adverse effects associated with aspirin, it can be replaced with clopidogrel.)

Group Type: ACTIVE_COMPARATOR

Pitavastatin 2 mg with aspirin 100 mg, taken once daily.

Intervention Type: DRUG

Moderate-intensity lipid-lowering therapy with aspirin

Interventions

Pitavastatin 4mg and ezetimibe 10mg, taken once daily

Intensive lipid-lowering therapy without aspirin

Intervention Type: DRUG

Pitavastatin 2 mg with aspirin 100 mg, taken once daily.

Moderate-intensity lipid-lowering therapy with aspirin

Intervention Type: DRUG

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

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asan Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Seung-Whan Lee, M.D., Ph.D.

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Asan Medical Center

Seoul, , South Korea

Site Status: RECRUITING

Countries

South Korea

Central Contacts

Seung-Whan Lee

Role: CONTACT

seungwlee@amc.seoul.kr

82230103170

Facility Contacts

Seung-Whan Lee, MD

Role: primary

seungwlee@amc.seoul.kr

Tae Oh Kim, MD

Role: backup

allldie_7@naver.com

Other Identifiers

2025-0193

Identifier Type: -

Identifier Source: org_study_id