Effect of High-intensity Statin With Ezetimibe COmbination theRapy Versus High-intensity sTatin Monotherapy After Percutaneous Coronary Intervention With Drug-eluting Stents; the ESCORT Trial

Study Overview
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Brief Summary
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This study sought to evaluate whether ezetimibe combination to high-intensity statin therapy will have more prominent beneficial effect compared to high-intensity statin monotherapy in patients who underwent coronary revascularization with newer generation drug-eluting stent (DES) implantation. Furthermore, the optimal OCT-based optimal expansion criteria as well as the efficacy and safety of newer generation will be investigated.

Detailed Description
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All eligible patients who underwent coronary revascularization with newer generation DES implantation will be enrolled according to inclusion/exclusion criteria after voluntary agreement with informed consent. At the time of enrollment, the investigators will stratify the patients according to LDL-cholesterol <100mg/dL, acute coronary syndrome, and DES type, and randomly assign them in two groups according to lipid-lowering therapy with a 1:1 ratio: Combination therapy group vs. Statin monotherapy group. In this study, four types of new generation DES will be used: Orsiro (Biotronik), Firehawk (Microport), Genoss (Genoss) or D+Storm (CGBIO). In this study, OCT substudy will be performed for the patients with diffuse long lesions requiring total stented length ≥40 mm (targeted for 1000 patients in the trial). Corresponding patients will be randomly assigned into two groups according to the OCT-based optimal expansion criteria with a 1:1 ratio: meeting Absolute expansion vs. Relative expansion. Absolute expansion criteria indicate minimum stent area (MSA) >4.5mm2 and relative expansion criteria indicate MSA > 80% of average reference lumen area. The patients will receive DES implantation under OCT guidance and stent optimization will be performed to satisfy each expansion criteria.

Official Title
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Effect of High-intensity Statin With Ezetimibe COmbination theRapy Versus High-intensity sTatin Monotherapy After Percutaneous Coronary Intervention With Drug-eluting Stents; the ESCORT Trial

Conditions
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Coronary Artery Disease Requiring Coronary Revascularization With Newer Generation DES Implantation

Intervention / Treatment
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* Drug: ezetimibe/high-intensity statin combination therapy (ezetimibe 10mg plus atoravastatin 40mg)
* Drug: high-intensity statin monotherapy (atoravastatin 40mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 19-85 years Patients who underwent coronary revascularization with newer generation DES implantation Exclusion Criteria: Allergy or hypersensitive to ezetimibe or statin Active liver disease or persistent unexplained serum AST/ALT elevation more than 2 times the upper limit of normal range History of any adverse drug reaction requiring discontinuation of statin Pregnant women, women with potential childbearing, or lactating women Life expectancy less than 3 years Inability to follow the patient over the period of 1 year after enrollment, as assessed by the investigator Inability to understand or read the informed consent

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination therapy group<br>Ezetimibe/high-intensity statin combination therapy | Drug: ezetimibe/high-intensity statin combination therapy (ezetimibe 10mg plus atoravastatin 40mg)<br>* The initial dose of lipid-lowering therapy will be ezetimibe 10mg plus atoravastatin 40mg. During follow-up, the dose of ezetimibe 10mg plus atoravastatin 40mg is strongly recommended to be maintained.<br>|
| Active Comparator: Statin monotherapy group<br>High-intensity statin monotherapy | Drug: high-intensity statin monotherapy (atoravastatin 40mg)<br>* The initial dose of lipid-lowering therapy will be atoravastatin 40mg. During follow-up, the dose of atoravastatin 40mg is strongly recommended to be maintained.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy of lipid lowering therapy | Composite of all-cause death, myocardial infarction (MI), any coronary revascularization, hospitalization for unstable angina, or nonfatal stroke within 3 years | Within 3 years after the enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving target LDL-cholesterol <55 mg/dL or 70 mg/dL at 6 weeks, 1, 2, and, 3 years |  | Within 3 years after the enrollment | 
| Rate of cross-over into the non-allocated therapy |  | Within 3 years after the enrollment | 
| Each component of primary endpoint A. All-cause death (percentage) |  | Within 3 years after the enrollment | 
| Each component of primary endpoint B. MI (percentage) |  | Within 3 years after the enrollment | 
| Each component of primary endpoint C. Any coronary revascularization (percentage) |  | Within 3 years after the enrollment | 
| Each component of primary endpoint D. Hospitalization for unstable angina (percentage) |  | Within 3 years after the enrollment | 
| Each component of primary endpoint E. Nonfatal-stroke (percentage) |  | Within 3 years after the enrollment | 
| Cardiac death (percentage) |  | Within 3 years after the enrollment | 
| Stent thrombosis (percentage) |  | Within 3 years after the enrollment | 
| Target-vessel revascularization (percentage) |  | Within 3 years after the enrollment | 
| Target-lesion revascularization (percentage) |  | Within 3 years after the enrollment | 
| BARC type 2-5 bleeding (percentage) |  | Within 3 years after the enrollment | 
| BARC type 3-5 bleeding (percentage) |  | Within 3 years after the enrollment | 
| Patient-oriented composite endpoint which is composite of all-cause death, MI, or any coronary revascularization (percentage) |  | Within 3 years after the enrollment | 
| Device-oriented composite endpoint which is composite of cardiovascular death, MI, or clinically-driven target-vessel revascularization (percentage) |  | Within 3 years after the enrollment | 
| Difference in antiplatelet therapy strategy (percentage) |  | Within 3 years after the enrollment | 
| Difference in high-ischemic risks (percentage) |  | Within 3 years after the enrollment | 
| Difference in high-bleeding risks (percentage) |  | Within 3 years after the enrollment | 
| different OCT optimization criteria when treating very long lesions | A. Primary endpoint (percentage) B. Stent thrombosis (percentage) C. Target-vessel revascularization (percentage) D. Target-lesion revascularization (percentage) E. Patient-oriented composite endpoint (percentage) F. Device-oriented composite endpoint ((percentage) | Within 3 years after the enrollment | 
| Safety endpoint related to lipid-lowering medication | A. New-onset DM, worsening of glycemic control or HOMA-index (percentage) B. Occurrence of SAMS requiring change of therapy regimen or dosage (percentage) C. Elevation of muscle enzymes which is creatine kinase > 4 x Upper Normal Limit (percentage) D. Elevation of hepatic enzymes which is aminotransferase > 3 x Upper Normal Limit (percentage) E. Elevation of serum creatinine level which is > 50% from baseline (percentage) F. Increase of proteinuria (percentage) G. Diagnosis of cancer (percentage) | Within 3 years after the enrollment |