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

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.

Study Overview

• Status: Recruiting
• Conditions: Coronary Artery Disease Requiring Coronary Revascularization With Newer Generation DES Implantation
• Intervention / Treatment: Drug: ezetimibe/high-intensity statin combination therapy (ezetimibe 10mg plus atoravastatin 40mg); Drug: high-intensity statin monotherapy (atoravastatin 40mg)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 4310
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Byeong-Keuk Kim; Phone Number: 82-2228-8460; Email: kimbk@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Yonsei University Health system, Severance Hospital
    • Contact: Byeong-Keuk Kim; Phone Number: 82-2228-8460; Email: kimbk@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 19-85 years
2. Patients who underwent coronary revascularization with newer generation DES implantation

Exclusion Criteria:

1. Allergy or hypersensitive to ezetimibe or statin
2. Active liver disease or persistent unexplained serum AST/ALT elevation more than 2 times the upper limit of normal range
3. History of any adverse drug reaction requiring discontinuation of statin
4. Pregnant women, women with potential childbearing, or lactating women
5. Life expectancy less than 3 years
6. Inability to follow the patient over the period of 1 year after enrollment, as assessed by the investigator
7. Inability to understand or read the informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination therapy group; Ezetimibe/high-intensity statin combination therapy	Drug: ezetimibe/high-intensity statin combination therapy (ezetimibe 10mg plus atoravastatin 40mg); 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.
Active Comparator: Statin monotherapy group; High-intensity statin monotherapy	Drug: high-intensity statin monotherapy (atoravastatin 40mg); 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Byeong-Keuk Kim, Severance Cardiovascular Hospital, Yonsei University Health System

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: January 29, 2023
• First Submitted That Met QC Criteria: March 21, 2023
• First Posted (Actual): March 24, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Ezetimibe; Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Other Study ID Numbers: 4-2022-1335

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No