Clinical trial NCT06722521: GUIDE-CAC: Intensive Lipid-Lowering Without Aspirin vs. Standard Therapy 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Primary Prevention
Vascular Calcification
Keywords: Cardiovascular Diseases
Aspirin
Statin
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
First posted: 2024-12-09
Enrollment: 7435
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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