Clinical trial NCT04826354: Effects of Statin for Elderly Patients With Atherosclerotic Cardiovascular Disease
Official title: Effects of High-dose StAtin Versus Low-dose Statin Plus Ezetimibe on Statin-Associated Muscle Symptoms & on Reaching Target LDL-C Levels Among Elderly Patients With Atherosclerotic Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atheroscleroses, Coronary
Keywords: Elderly
Statin
Ezetimibe
Lead sponsor: Korea University Anam Hospital
Sponsor class: OTHER
First posted: 2021-04-01
Enrollment: 582
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Effects of high-dose Statin Versus low-dose statin plus ezetimibe on statin-associated Muscle Symptoms
Primary purpose: TREATMENT

Brief summary: High-dose statins can reduce mortality and cardiovascular events in patients with established atherosclerotic cardiovascular disease (ASCVD). Therefore, US and European recommendations recommend that established ASCVD patients (coronary artery disease, cerebrovascular disease, peripheral vascular disease) use high-dose statins to lower LDL cholesterol levels by at least 50%. However, in actual practice, high-dose statins are relatively less used, and the reason is unclear, but it is believed to be due to concerns about the side effects of high-dose statins. Most of the side effects of statins are statin-associated muscle symptoms (SAMS), which are more common than the incidence in clinical studies, especially in frontline care. These muscle side effects are dose-dependent and are common at high doses, and the incidence is known to increase in the elderly over 70 years of age. However, the US recommendation recommends using high-dose statins to lower LDL cholesterol by 50% or more to prevent cardiovascular events even in ASCVD patients over 70 years of age.

Most early studies on lowering LDL cholesterol in ASCVD patients used high doses of statins. However, after introducing cholesterol absorption inhibitors ezetimibe and PCSK9 inhibitor, large-scale clinical studies have been conducted to lower LDL cholesterol using these drugs. In this study, as in the statin study, cardiovascular events were significantly reduced, and together with statins, it became a standard treatment for ASCVD patients. On the other hand, the clinical benefit shown in clinical studies using cholesterol-lowering agents so far depends entirely on how much LDL cholesterol is lowered and how long it is maintained in a low state, indicating that LDL cholesterol management is the core of arteriosclerosis treatment. In addition to high-dose statins, a combination of low-dose statins and ezetimibe can be cited as a method for lowering LDL cholesterol to more than 50%. In the latter case, it is expected that there will be an advantage of reducing muscle side effects by reaching the target LDL cholesterol level by using a low-dose statin. However, no studies compare the difference in muscle side effects between low-dose statins and ezetimibe combination drugs, which reduce LDL cholesterol to the same extent compared to high-dose statins, in elderly patients over 70 years of age with ASCVD. In this study, the association of low-dose rosuvastatin 5mg and ezetimibe combination (rosuvastatin 10/5mg) compared to high-dose rosuvastatin 20mg in elderly patients 70 years of age or older with established ASCVD. This study aims to compare and analyze the incidence of muscle symptoms (SAMS) and their effect on LDL cholesterol.

Detailed description: Established Atherosclerotic Cardiovascular Disease (ASCVD)

A. Coronary artery disease meeting at least one of the following criteria:

* A history of coronary recanalization in multivessel coronary artery disease, evidenced by any of the following:

  1. Percutaneous coronary intervention (PCI) of one or more vessels, including branching arteries
  2. PCI or coronary artery bypass grafting (CABG) for \>50% residual stenosis in separate vessels that have not undergone recanalization
  3. multivessel CABG at least 5 years prior to screening
* Significant coronary without prior revascularization, evidenced by \>70% stenosis in at least one coronary artery, \>50% stenosis in two or more coronary arteries, or \>50% stenosis in the left main coronary artery arterial disease
* Known coronary calcium score \> 100 in subjects who did not undergo coronary recanalization prior to randomization

B. Cerebrovascular Disease meeting at least one of the following criteria:

* Previous transient ischemic attack with carotid artery stenosis in 50%
* 70% internal or external carotid artery stenosis or \>50% stenosis of two or more
* Past history of recanalization of internal or external carotid artery

C. Peripheral arterial disease meeting at least one of the following criteria:

* \> 50% stenosis in the arteries of the extremities
* History of abdominal aortic treatment (percutaneous or surgical) for atherosclerotic disease
* Ankle Brachial Index (ABI) ≤ 0.90

Eligibility criteria: Inclusion Criteria (must satisfy all of the following selection criteria) :

1. Those who are 70 years of age or older as of the date of consent
2. Established arteriosclerotic cardiovascular disease (coronary artery disease, cerebrovascular disease, or peripheral vascular disease)
3. Subjects who have consented to the study plan and follow-up observation by the patient or representative, and who consented in advance in writing to the clinical subject consent approved by the research deliberation committee/ethics committee of the research institution

Exclusion Criteria:

1. Take statins or ezetimibe within the last 4 weeks
2. In case of end-stage kidney disease (eGFR\<30 ml/min/1.73m2)
3. Heart surgery or major surgery is planned within the next 6 months
4. Patients with chronic diseases such as severe lung disease, stroke, etc.
5. Patients with chronic inflammatory diseases who require oral, intravenous, or intra-articular steroid treatment (Ointments, inhalants, or intranasal steroids are allowed)
6. If you have been diagnosed with cancer within the past 1 year or are currently receiving chemotherapy
7. In the case of clinically significant abnormal findings that may infringe on the safety of the study by the investigator's judgment confirmed in a screening visit, physical examination, blood test, or electrocardiogram
8. Liver disease, bile duct obstruction, or liver enzyme level (ALT/AST) is more than 3 times normal
9. If you have a disease whose life expectancy is less than 1 year
10. If you do not want or cannot comply with the procedure described in the research proposal

Primary outcomes:
measure: Statin-Associated Muscle Symptoms (SAMS)
timeFrame: 6 month
measure: Target Low density lipoprotein cholesterol (LDL-C) achievement
timeFrame: 6 month
Secondary outcomes:
measure: CK levels
timeFrame: 6 month
measure: GOT levels
timeFrame: 6 month
measure: GPT levels
timeFrame: 6 month
measure: Levels of Total cholesterol, LDL cholesterol, HDL cholesterol
timeFrame: 6 month
measure: Level of Triglyceride
timeFrame: 6 month
measure: Level of high sensitive-CRP
timeFrame: 6 month
measure: Incidence of myopathy, rhabdomyolysis
timeFrame: 6 month
measure: Frequency of drug discontinuation due to SAMS side effects
timeFrame: 6 month
measure: Frequency of drug discontinuation due to side effects other than SAMS
timeFrame: 6 month
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
Study officials:
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