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
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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
7,435
Intensive lipid-lowering therapy without aspirin
Moderate-intensity lipid-lowering therapy with aspirin
Asan Medical Center
Seoul, South Korea
RECRUITINGEvent rate of a major adverse cardiovascular events
Death from any cause, myocardial infarction, stroke, urgent coronary revascularization, resuscitated cardiac arrest, or unstable angina related hospitalization
Time frame: 48months
Event rate of a all cause death
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.
Time frame: 48months
Event rate of a cardiovascular death
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
Time frame: 48months
Event rate of a spontaneous myocardial infarction
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
Time frame: 48months
Event rate of a stroke
A. Ischemic Stroke B. Hemorrhagic Stroke C. Undetermined Stroke
Time frame: 48months
Event rate of a urgent coronary revascularization
1. Elective: 2. Urgent: 3. Emergency: 4. Salvage:
Time frame: 48months
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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)
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
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)
Time frame: 48months