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Comparative Study of Rosuvastatin/Ezetimib 20/10 mg and Atovastatin/Ezetimib 40/10 mg (TOLERANT Trial)

Phase 4
Recruiting
Conditions
Coronary Artery Disease
Dyslipidemias
Interventions
Drug: a high dose of statin/ezetimib
Registration Number
NCT05910476
Lead Sponsor
Yonsei University
Brief Summary

the investigators would like to compare the differences between roschvastin and atovastatin in patients who require high-dose statin/ejetimib to undergo a new generation of drug elution stent implantation for cardiovascular disease and maintain LDL cholesterol below 55 mg/dL.

Detailed Description

Death from vascular disease accounts for about one-third of all causes of death. Important regulatory factors in cardiovascular disease include dyslipidemia, high blood pressure, and diabetes, and keeping LDL cholesterol low among dyslipidemia levels, especially after cardiovascular stent treatment, is an essential factor to prevent another event in the future. Statin is currently the most widely used LDL cholesterol control drug with multifunctional effects such as controlling inflammatory reactions, controlling the movement and proliferation of vascular smooth muscle cells, and inhibiting the production of blood clots in addition to LDL cholesterol control.In addition, in several clinical studies, statins have shown many effects in primary and secondary prevention of cardiovascular disease, and several studies have been published that lower LDL cholesterol results in more benefits. Based on these findings, the 2016 European Heart Association (ESC), 2018 American Heart Association (ACC), and most recently changed 2022 Korean guidelines recommend controlling LDL cholesterol to \<55mg/dL for patients with coronary artery disease. However, high-dose statins alone are still difficult to maintain for a long time due to increased liver levels, diabetes, and muscle pain, and recently, a drug that lowers LDL cholesterol has been developed in the small intestine called Ezetimib and is widely used in combination with statins in actual clinical trials. In fact, the RACING trial published in LANCET for domestic patients reported that the combination of moderate-intensity statins (Rosuvastatin 10mg) and ezetimib had fewer side effects for three years and better compliance, resulting in a better rate of maintaining LDL cholesterol at 70mg/dL or less than high-intensity statins alone. However, in this study, the rate at which LDL cholesterol remained below 55 mg/dL after one year was only 42% for moderate statins/esetimibe and 25% for high-intensity statins, and remained similar for three years. Therefore, high-intensity statins and ezetimibes may be essential treatments to reduce LDL cholesterol to less than 55 mg/dL and more than 50% under the current new guidelines. High-strength statins usually refer to more than 40 mg of atovastatin and 20 mg of Rosuvastatin, and drugs that combine ezetimibe with these high-strength statins are currently widely used to lower LDL cholesterol to 55 mg/dL or less if there are no special side effects in clinical practice, but research on compliance is very insufficient. This study aims to observe the rate of discontinuation or intolerance in patients taking Rosuvastatin/Ezetimib 20/10mg and Atovastatin/Ezetimib 40/10mg, with no previous comparison, RACING trial reported a 5% rate of discontinuation at rosuvastain 20mg administered, and atovatin/10mg/10mg. Referring to On the use of a pilot sample for sample size determination. the hospital conducts about 60 PCI cases a month, and about 1/5 of them are expected to be able to enroll 100 patients per group for about two years to conduct a total of 200 patients.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
200
Inclusion Criteria
  1. 19 years of age or older
  2. Patients who underwent a new generation of drug elution stent implantation for cardiovascular disease
Exclusion Criteria
  1. LDL cholesterol levels below 55 mg/dL without statin treatment
  2. Serum AST/ALT with an acute liver disease within a month or a normal upper limit that is not continuously explained
  3. Allergies or overreactions to statins
  4. Estimated Dawn of Less than 1 Year
  5. If it is determined that follow-up is not possible for more than one year
  6. Pregnancy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
rosuvastatin/ezetimibe 20/10mga high dose of statin/ezetimibrosuzet 10/20mg
atorvastatin/ezetimibe 40/10mga high dose of statin/ezetimibNB zet 10/40mg
Primary Outcome Measures
NameTimeMethod
Percentage of statins changed12 months

Percentage of statins changed to discontinuation or intolerance (muscle pain, muscle efficiency, elevated liver level, etc.) within a year

Rate at which LDL cholesterol remains below 55 mg/dL12 months

Rate at which LDL cholesterol remains below 55 mg/dL in all 1-year blood tests

Secondary Outcome Measures
NameTimeMethod
number of non-fatal myocardial infarction12 months

number of non-fatal myocardial infarction

number of coronary artery re-perfusion12 months

number of coronary artery re-perfusion

Increased muscle enzyme aberration12 months

Increased muscle enzyme aberration (CPK \> 4 x normal upper limit)

number of Major bleeding12 months

number of Major bleeding

Elevated serum creatine levels12 months

Elevated serum creatine levels (from \>50% baseline)

number of people who stopped taking the drug12 months

number of people who stopped taking the drug

number of Newly developed diabetes or difficulty in controlling sugar12 months

number of Newly developed diabetes or difficulty in controlling sugar

occurrence of statin-related muscle symptoms requiring therapeutic or dose changes12 months

occurrence of statin-related muscle symptoms requiring therapeutic or dose changes

The rate at which LDL cholesterol is maintained at 55 mg/dL in the blood test after a month1 months

The rate at which LDL cholesterol is maintained at 55 mg/dL in the blood test after a month

Cardiovascular death12 months

Cardiovascular death

number of non-fatal stroke12 months

number of non-fatal stroke

Elevated liver enzyme levels12 months

Elevated liver enzyme levels (AST, ALT, or both ≥ 3 x normal upper bound)

Trial Locations

Locations (1)

Yongin Severance Hospital

🇰🇷

Yongin, Gyeonggi-do, Korea, Republic of

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