Effects of Ezetimibe Combination Therapy for Patients With Atherosclerotic Cardiovascular Disease; Randomized Comparison of LDL-cholesterol Targeting <70 Versus <55mg/dL; Ez-PAVE Trial

NCT04626973 | Completed DMC

• 1 other identifier: 4-2020-0903
• Study Type: interventional
• Target: 3,048
• Locations: 1 country
• Sites: 1

Brief Summary

Although the clinical efficacy of LDL-cholesterol lowering therapy has been proven with strong evidences and emphasized, there are also growing concerns that intensive lipid-lowering therapy would be related to increased risk of adverse effects. In addition, statin potency from recent guidelines was set from the studies composed of mainly Caucasian population, although there is an inconsistency of statin effect according to ethnicity. Asian population showed more profound LDL reduction not only from high potent statin but also from moderate to low potent statin. Conventional strategies for lowering LDL-cholesterol focused on statins, therefore doubling of previously described dose of statin would be common way in patients with inadequate LDL-cholesterol levels. Adding ezetimibe will be an alternative strategy not only to lower LDL-cholesterol level and also to reduce the need of dosage of high-intensity statin to achieve sufficient LDL-cholesterol lowering effect. However, studies regarding the effect of intensive-targeting of lipid-lowering therapy and therapy regimens are lacking. Thus, on these basis, we sought to evaluate whether intensive-targeting of lipid-lowering therapy will have more prominent beneficial effect compared to conventional-targeting in patients with documented ASCVD with either an ezetimibe/statin combination therapy or a statin monotherapy.

Conditions

Atherosclerotic Cardiovascular Disease

Keywords

Dyslipidemia; ASCVD; Coronary artery disease

Outcome Measures

Primary Outcomes (1)

• Clinical outcomes by different lipid-lowering therapy

  Composite of cardiovascular death, non-fatal MI, non-fatal stroke, any revascularization, and hospitalization for unstable angina

  Within 3 years after the enrollment

Secondary Outcomes (16)

• Each component of primary endpoint within 3 years

  Within 3 years after the enrollment

• Various composite outcomes within 3 years

  Within 3 years after the enrollment

• Proportion of subjects achieving target LDL-cholesterol level

  Within 3 years after the enrollment

• Rate of cross-over into the non-allocated therapy regimen in order to achieve target LDL-cholesterol level

  Within 3 years after the enrollment

• Proportions of subjects requiring proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to achieve target LDL-cholesterol level

  Within 3 years after the enrollment

Study Arms (2)

Intensive-targeting group

EXPERIMENTAL

Drug: Ezetimibe/Statin Combination therarpy (ezetimibe plus rosuvastatin); Drug: Statin monotherapy (rosuvastatin or atorvastatin)

Conventional-targeting group

ACTIVE COMPARATOR

Drug: Ezetimibe/Statin Combination therarpy (ezetimibe plus rosuvastatin); Drug: Statin monotherapy (rosuvastatin or atorvastatin)

Interventions

Ezetimibe/Statin Combination therarpy (ezetimibe plus rosuvastatin) DRUG

For statin naive patients, patients would initially receive Ezetimibe 10mg plus Rosuvastatin 10 or 20 mg. For non-statin naive patients, regimens are to be changed to the equivalent dose of ezetimibe+rosuvastatin combination in case of already achieved LDL-cholesterol target (\<55 mg/dL) and to be dosed up than the equivalent dose of study drugs in case of not yet achieved LDL-cholesterol target.

Intensive-targeting group

Statin monotherapy (rosuvastatin or atorvastatin) DRUG

For statin naive patients, patients would initially receive Rosuvastatin 20mg or Atorvastatin 40 or 80 mg. For non-statin native patients, regimens are to be change to equivalent dose of atorvastatin or rosuvastatin in case of already achieved LDL-cholesterol target (\<55 mg/dL) and to be dosed up than the equivalent dose of study drugs in case of not yet achieved LDL-cholesterol target.

Intensive-targeting group

Eligibility Criteria

• Age: 19 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 19-80 years
• Documented atherosclerotic cardiovascular disease (ASCVD)
• Previous acute coronary syndrome (myocardial infarction \[MI\] or unstable angina),
• Or stable angina with imaging or functional studies
• Or coronary revascularization (percutaneous coronary intervention \[PCI\], coronary artery bypass graft \[CABG\], and other arterial revascularization procedures)
• Or stroke and transient ischemic attack (TIA)
• Or peripheral artery disease

You may not qualify if:

• LDL-cholesterol level less than 70 mg/dL without statin therapyAllergy 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
• Allergy or hypersensitivity to any statin or ezetimibe
• Solid organ transplantation recipient
• 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 content

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine

Seoul, South Korea

Location

MeSH Terms

Conditions

Atherosclerosis; Dyslipidemias; Coronary Artery Disease

Interventions

Ezetimibe; Rosuvastatin Calcium; Atorvastatin

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Pyrroles; Azoles; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Byeong-Keuk Kim, MD, PhD

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: At the time of enrollment, we will stratify all patients according to LDL-cholesterol \<100mg/dL, DM, and acute coronary syndrome, and randomly assign them in two groups according to LDL-cholesterol targeting level with a 1:1 ratio: "Intensive-targeting group" vs. "Conventional-targeting group". In addition, patients in each group will be randomly assigned to receive two lipid-lowering therapy regimen with a 1:1 ratio: "Ezetimibe/Statin combination therapy" vs. "Statin monotherapy".

Study Record Dates

• First Submitted: October 20, 2020
• First Posted: November 13, 2020
• Study Start: January 15, 2021
• Primary Completion: September 24, 2025
• Study Completion: September 24, 2025
• Last Updated: November 17, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)