Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
All eligible patients who have documented ASCVD will be enrolled according to inclusion/exclusion criteria after voluntary agreement with informed consent. 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". Patients allocated to each treatment group will receive lipid-lowering therapy with following protocols.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intensive-targeting group | Experimental |
| |
| Conventional-targeting group | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Each component of primary endpoint within 3 years |
| Within 3 years after the enrollment |
| Various composite outcomes within 3 years |
Not provided
Inclusion Criteria:
Age 19-80 years
Documented atherosclerotic cardiovascular disease (ASCVD)
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Byeong-Keuk Kim, MD, PhD | Severance Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Division of Cardiology, Yonsei Cardiovascular Hospital, Yonsei University College of Medicine | Seoul | South Korea |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41910315 | Derived | Lee YJ, Lee SJ, Kim JW, Lee SH, Kim GS, Park JH, Cho JM, Kang WC, Yoon HJ, Kim WH, Lee SJ, Lee JB, Jang JY, Shin S, Park IH, Kwon SU, Kim S, Hong SJ, Ahn CM, Kim JS, Ko YG, Choi D, Hong MK, Jang Y, Kim BK; Ez-PAVE Investigators. Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease. N Engl J Med. 2026 Apr 9;394(14):1365-1375. doi: 10.1056/NEJMoa2600283. Epub 2026 Mar 28. |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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".
Not provided
Not provided
Not provided
Not provided
|
| 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. |
|
| Ezetimibe/Statin Combination therarpy (ezetimibe plus rosuvastatin) | Drug | For statin naive patients, patients would initially receive Ezetimibe 10mg plus Rosuvastatin 5 or 10mg. 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 (<70 mg/dL) and to be dosed up than the equivalent dose of study drugs in case of not yet achieved LDL-cholesterol target. |
|
| Statin monotherapy (rosuvastatin or atorvastatin) | Drug | For statin naive patients, patients would initially receive Rosuvastatin 10 or 20mg or Atorvastatin 20 or 40mg. 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 (<70 mg/dL) and to be dosed up than the equivalent dose of study drugs in case of not yet achieved LDL-cholesterol target. |
|
|
| 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 |
| Difference in rate of primary outcome according to sex | Within 3 years after the enrollment |
| Difference in rate of primary outcome according to body mass index | Within 3 years after the enrollment |
| Rate of New-onset diabetes mellitus | Within 3 years after the enrollment |
| Rate of worsening of glycemic control or homeostatic model assessment (HOMA)-index | Within 3 years after the enrollment |
| Occurrence of statin-associated muscle symptoms (SAMS) requiring change of therapy regimen or dosage | Within 3 years after the enrollment |
| Occurence of elevation of muscle enzymes (CPK > 4 x UNL) | Within 3 years after the enrollment |
| Occurence of elevation of hepatic enzymes (AST, ALT, or both ≥ 3 x UNL) | Within 3 years after the enrollment |
| Occurence of elevation of serum creatinine level (>50% from baseline) | Within 3 years after the enrollment |
| Change of proteinuria | Within 3 years after the enrollment |
| Rate of cancer diagnosis | Within 3 years after the enrollment |
| Rate of operation due to cataract | Within 3 years after the enrollment |
| ID | Term |
|---|---|
| D050197 | Atherosclerosis |
| D050171 | Dyslipidemias |
| D003324 | Coronary Artery Disease |
| ID | Term |
|---|---|
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D052439 | Lipid Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069438 | Ezetimibe |
| D000068718 | Rosuvastatin Calcium |
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D001384 | Azetidines |
| D001385 | Azetines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
Not provided
Not provided