NCT04626973

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

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 3,048 (actual)
• Sponsor: Yonsei University · Academic / Other
• Sex: All
• Age: 19 Years – 80 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Atherosclerotic Cardiovascular Disease

Interventions

Type	Name	Description
DRUG	Ezetimibe/Statin Combination therarpy (ezetimibe plus rosuvastatin)	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.
DRUG	Statin monotherapy (rosuvastatin or atorvastatin)	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.
DRUG	Ezetimibe/Statin Combination therarpy (ezetimibe plus rosuvastatin)	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.
DRUG	Statin monotherapy (rosuvastatin or atorvastatin)	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.

Timeline

• Start date: 2021-01-15
• Primary completion: 2025-09-24
• Completion: 2025-09-24
• First posted: 2020-11-13
• Last updated: 2025-11-17

Locations

1 site across 1 country: South Korea