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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.
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, we 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 ≥30 mm (targeted for 700 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". The absolute expansion criteria is defined as a minimum stent area (MSA) >4.5mm2, while the relative expansion criteria is defined as achieving an MSA ≥ 80% of the mean reference lumen area or ≥ 100% of the distal reference lumen area. The patients will receive DES implantation under OCT guidance and stent optimization will be performed to satisfy the assigned expansion criteria.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combination therapy group | Experimental | Ezetimibe/high-intensity statin combination therapy |
|
| Statin monotherapy group | Active Comparator | High-intensity statin monotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ezetimibe/high-intensity statin combination therapy (ezetimibe 10mg plus atoravastatin 40mg) | Drug | 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. |
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Byeong-Keuk Kim | Contact | 82-2228-8460 | kimbk@yuhs.ac |
| Name | Affiliation | Role |
|---|---|---|
| Byeong-Keuk Kim | Severance Cardiovascular Hospital, Yonsei University Health System | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yonsei University Health System, Severance Hospital | Recruiting | Seoul | South Korea |
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|
| high-intensity statin monotherapy (atoravastatin 40mg) | Drug | 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. |
|
| 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 |
| ID | Term |
|---|---|
| D000069438 | Ezetimibe |
| ID | Term |
|---|---|
| D001384 | Azetidines |
| D001385 | Azetines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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