GUIDE-CAC: Intensive Lipid-Lowering Without Aspirin vs. Standard Therapy With Aspirin in High Coronary Calcification.

Phase 4

Not yet recruiting

• Conditions: Primary Prevention; Vascular Calcification
• Interventions: Drug: Pitavastatin 4mg and ezetimibe 10mg, taken once daily; Drug: Pitavastatin 2 mg with aspirin 100 mg, taken once daily.

• Registration Number: NCT06722521
• Lead Sponsor: Asan Medical Center

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.

Study Timeline

• Study First Submitted: 2024-12-04
• Study First Submitted QC: 2024-12-04
• Study First Posted: 2024-12-09
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16
• Study Start: 2025-06-01
• Primary Completion: 2032-06-30
• Study Completion: 2032-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 7435

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive lipid-lowering therapy without aspirin	Pitavastatin 4mg and ezetimibe 10mg, taken once daily	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)
Statin Monotherapy with Aspirin	Pitavastatin 2 mg with aspirin 100 mg, taken once daily.	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.)

Primary Outcome Measures

Name	Time	Method
Event rate of a major adverse cardiovascular events	48months	Death from any cause, myocardial infarction, stroke, urgent coronary revascularization, resuscitated cardiac arrest, or unstable angina related hospitalization

Secondary Outcome Measures

Name	Time	Method
Event rate of a all cause death	48months	All-cause mortality was used instead of cardiac mortality to avoid potentially difficult adjudication of causes of death, especially given the relatively low expected mortality rate. In addition, the cause of death will be adjudicated as being due to cardiovascular causes, non-cardiovascular causes, or undetermined causes.
Event rate of a cardiovascular death	48months	includes death resulting from an acute myocardial infarction (MI), sudden cardiac death, death due to heart failure (HF), death due to stroke, death due to cardiovascular (CV) procedures, death due to CV hemorrhage, and death due to other CV causes
Event rate of a spontaneous myocardial infarction	48months	A spontaneous myocardial infarction related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection, resulting in intraluminal thrombus in one or more of the coronary arteries
Event rate of a stroke	48months	A. Ischemic Stroke B. Hemorrhagic Stroke C. Undetermined Stroke
Event rate of a urgent coronary revascularization	48months	1. Elective: 2. Urgent: 3. Emergency: 4. Salvage:
Event rate of a Resuscitated cardiac arrest	48months
Event rate of a unstable angina related hospitalization	48months
Event rate of a composite of hard outcomes (all cause death, myocardial infarction and ischemic stroke)	48months
Event rate of a Clinically relevant bleeding (Bleeding Academic Research Consortium definition ≥ type 2)	48months	Bleeding Academic Research Consortium definition ≥ type 2
Changes of Lipid profile	48months
Treatment-emergent Serious Adverse Events resulting in Study Drug Discontinuation	48months	Liver function abnormalities(AST or ALT \> 5x ULN); Renal function abnormalities (serum creatinine increase ≥3-fold from baseline OR increase to ≥4.0 mg/dL OR initiation of renal replacement therapy); Muscle-related events (Statin-associated muscle symptoms OR CK \>5x ULN) (CK reference range: 50-250 IU/L)