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

Official title

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

Overview

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.

Interventions

• Drug Pitavastatin 4mg and ezetimibe 10mg, taken once daily
  Intensive lipid-lowering therapy without aspirin
• Drug Pitavastatin 2 mg with aspirin 100 mg, taken once daily.
  Moderate-intensity lipid-lowering therapy with aspirin

Primary outcome measures

• Event rate of a major adverse cardiovascular events [Time frame: 48months]

Secondary outcome measures (11)

• Event rate of a all cause death [Time frame: 48months]
• Event rate of a cardiovascular death [Time frame: 48months]
• Event rate of a spontaneous myocardial infarction [Time frame: 48months]
• Event rate of a stroke [Time frame: 48months]
• Event rate of a urgent coronary revascularization [Time frame: 48months]
• Event rate of a Resuscitated cardiac arrest [Time frame: 48months]
• Event rate of a unstable angina related hospitalization [Time frame: 48months]
• Event rate of a composite of hard outcomes (all cause death, myocardial infarction and ischemic stroke) [Time frame: 48months]
• Event rate of a Clinically relevant bleeding (Bleeding Academic Research Consortium definition ≥ type 2) [Time frame: 48months]
• Changes of Lipid profile [Time frame: 48months]
• Treatment-emergent Serious Adverse Events resulting in Study Drug Discontinuation [Time frame: 48months]

Eligibility criteria

Inclusion criteria

• Adults aged 19 years and older
• 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
• Participants will be eligible for inclusion regardless of prior statin or anti-platelet agents use.

Exclusion criteria

• 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
• 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
• Patients with familial hypercholesterolemia.
• Patients with low-density lipoproteins cholesterol (LDL-C) ≥ 190 mg/dL regardless taking a statin or not.
• Continuation of PCSK9 inhibitor is required during the clinical trial
• Patients with chronic kidney disease (<eGFR 30mL/min/1.73m2)
• Advanced liver disease (Child-Pugh B or C)
• Hepatic disease or biliary tract obstruction, or significant hepatic enzyme elevation (ALT or AST > 5 times upper limit of normal).
• History of gastrointestinal bleeding, peptic ulcer, or intracranial hemorrhage within 6 months prior screening
• Patients with a history of organ transplantation who are on immunosuppressive therapy
• Concurrent use of other medications that may increase bleeding risk such NOAC and warfarin
• A history of significant allergic reaction to aspirin or statin/ezetimibe
• 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.
• Life expectancy < 1 years for any non-cardiac or cardiac causes.
• Patient's pregnant or breast-feeding or child-bearing potential.
• 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.
• Unwillingness or inability to comply with the procedures described in this protocol

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

South Korea · 1 center

• Asan Medical Center — Seoul

Identifiers

NCT: NCT06722521 · 2025-0193

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗