Clinical trial NCT05845424: High-intensity Statin and Ezetimibe Therapy for Asymptomatic Patients With Positive Coronary Calcium
Official title: Comparison of Efficacy and Safety of High-Intensity Statin and Ezetimibe Combination Versus StanDard carE in AsymptomatiC PatIentS wIth Presence of COroNary Artery CALCIUM (DECISION-CAL)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Coronary Artery Calcification
Metabolic Syndrome
Dyslipidemias
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2023-05-06
Enrollment: 6000
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: standard treatment vs. aggressive treatment
Primary purpose: TREATMENT

Brief summary: The aim of this study is to compare safety and efficacy between the aggressive treatment with combination of high-intensity statin and ezetimibe and the current standard lipid lowering treatment in asymptomatic patients with presence of coronary calcification.

Detailed description: Atherosclerotic cardiovascular diseases (ASCVD), such as myocardial infarction (MI), ischemic stroke, or peripheral arterial disease, are the leading cause of morbidity and mortality worldwide. The causality of low-density lipoproteins cholesterol (LDL-C) level in the development of ASCVD is well demonstrated in previous studies. After introducing LDL-C lowering agents, multiple large-scale randomized clinical trials have demonstrated lower cardiovascular events with lowering LDL-C levels. In particular, for secondary prevention, more aggressive control of LDL-C levels with high-intensity statin therapy significantly reduced cardiovascular events compared with moderate-intensity statin therapy. In addition, the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) proved the clinical efficacy of additive ezetimibe for incrementally lowering of LDL-C levels in patients with acute coronary syndrome. However, there has been limited evidence regarding the efficacy and safety of aggressive lipid-lowering strategy using high-intensity statin with a combination of ezetimibe for primary prevention of cardiovascular events among persons without cardiovascular disease. Although the Heart Outcomes Prevention Evaluation (HOPE)-3 and Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trials consistently identified that the use of rosuvastatin (10 mg or 20 mg) was significantly associated with reduced future risk of major cardiovascular events in patients who did not have cardiovascular disease, those studies have been focused on the use of statin, not on the intensity of statin.

The coronary artery calcium (CAC) scan, a marker of subclinical coronary atherosclerosis, has become popular for individuals at risk for atherosclerotic cardiovascular disease. CAC is strongly associated with atherosclerotic burden and predicts coronary heart disease events and mortality, regardless of their age, sex, race, or ASCVD risk. Furthermore, the progression of CAC is associated with an increased risk for future hard and total coronary heart disease events. The use of CAC scoring was associated with significant improvements in the reclassification and discrimination of incident ASCVD. Nevertheless, the current guidelines recommend CAC measurement for selected cases only with borderline or intermediate risk of ASCVD to guide the use of statin or not. However, in real-world practice, CAC testing is increasingly being promoted to the public as a means of self-assessment of cardiovascular risk and is widely being used regardless of ASCVD risk. Considering that statin has additional properties, including atherosclerotic plaque stabilization, oxidative stress reduction, enhancement of endothelial function, and a decrease in vascular inflammation beyond their lipid-lowering effect, aggressive treatment with a high-intensity statin plus ezetimibe combination might have beneficial effects on the long-term clinical outcomes for asymptomatic patients with significant coronary calcium (Agatston Score ≥ 100) compared with standard lipid-lowering therapy endorsed by the current guidelines.

Therefore, the purpose of DECISION-CALCIUM (Comparison of Efficacy and Safety of High-Intensity Statin and Ezetimibe Combination versus StanDard carE in AsymptomatiC PatIentS wIth Presence of COroNary Artery CALCIUM) trial is to compare the efficacy and safety of the aggressive lipid-lowering therapy with combination of high-intensity statin and ezetimibe, compared with the current standard lipid-lowering therapy in asymptomatic patients with significant coronary calcification for primary prevention.

Eligibility criteria: Inclusion Criteria:

* Subject must be at least 40 years of age.
* Asymptomatic patients with presence of coronary calcification (Agatston Score ≥ 100)
* low-density lipoproteins cholesterol (LDL-C) \<190 mg/dL

Exclusion Criteria:

* Objective evidence of at least moderate inducible ischemia requiring revascularization treatment
* History of cerebrovascular disease
* History of coronary or peripheral arterial revascularization
* Active liver disease or persistent unexplained serum transaminase elevations more than 2 times the upper limit of normal range
* History of any adverse drug reaction requiring discontinuation of statin (e, g. rhabdomyolysis)
* Allergy or sensitivity to any statin or ezetimibe
* Concurrent treatment with cyclosporine or a condition likely to result in organ transplantation and the need for cyclosporine
* Pregnancy or breast feeding
* Non-cardiac co-morbid conditions are present with life expectancy \<1 year or that may result in protocol non-compliance (per site investigator's medical judgment)
* Unwillingness or inability to comply with the procedures described in this protocol.

Primary outcomes:
measure: Major adverse cardiovascular events
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
Secondary outcomes:
measure: All-cause death
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Cardiovascular death
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Stroke
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Unplanned coronary revascularization
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Arterial revascularization procedure
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Major bleeding
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Bleeding
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Heart failure hospitalization
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Coronary calcium progression
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Changes of LDL-C
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: New-onset diabetes mellitus
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Hepatic disorder requiring discontinuation of statin
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: muscle-related adverse events
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Proportion of patients with LDL-C < 100mg/dL
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
measure: Proportion of patients with LDL-C < 70mg/dL
timeFrame: up to 4.5 years of median follow-up (till 3 year after the last patient enrollment)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: SamsungMedicalCenter
Study officials:
affiliation: Samsung Medical Center
name: Seung-Hyuk Choi
role: PRINCIPAL_INVESTIGATOR
References: