Effects of Statin for Elderly Patients With Atherosclerotic Cardiovascular Disease

August 6, 2023 updated by: Soon Jun Hong, Korea University Anam Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

582

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Korea, Republic of
      • Seoul, Korea, Republic of
        • Korea University Anam Hospital
      • Seoul, Korea, Republic of
        • Kangbuk Samsung Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

70 years and older (Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rosuvastatin
Rosuvastatin 20mg
Drug: Rosuvastatin
Rosuvastatin
Active Comparator: Rosuvamibe
Rosuvastatin plus ezetimibe 10/5
Drug: Rosuvastatin and Ezetimibe
Rosuvastatin Versus Rosuvastatin plus Ezetimibe

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Statin-Associated Muscle Symptoms (SAMS)
Time Frame: 6 month

Patients with a Proposed Statin Myalgia Index score of 7 or higher (Cardiovasc Drugs Ther 2003;17:459-465):

  • Aspects: muscle pain, muscle spasms, muscle stiffness, feeling of strength, ligament pain, etc.
  • Location: thigh, buttocks, calves, back muscle, proximal arms
  • Onset time after dosing: within 6 months
  • Deteriorating factors: exercise, rest, cold exposure, position change, fasting
  • Severe: Occurs in abnormalities in daily life, occurs in daily life, occurs in less than daily life
6 month
Target Low density lipoprotein cholesterol (LDL-C) achievement
Time Frame: 6 month
Target LDL-C achievement (LDL <70mg/dL)
6 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CK levels
Time Frame: 6 month
Creatinine Kinase levels
6 month
GOT levels
Time Frame: 6 month
Aspartate Transaminase (Glutamic Oxaloacetic Transaminase levels
6 month
GPT levels
Time Frame: 6 month
Alanine Transaminase (Glutamic Pyruvic Transaminase) levels
6 month
Levels of Total cholesterol, LDL cholesterol, HDL cholesterol
Time Frame: 6 month
Levels of Total cholesterol, LDL cholesterol, HDL cholesterol
6 month
Level of Triglyceride
Time Frame: 6 month
Level of Triglyceride
6 month
Level of high sensitive-CRP
Time Frame: 6 month
Level of high sensitive-CRP
6 month
Incidence of myopathy, rhabdomyolysis
Time Frame: 6 month
Incidence of myopathy, rhabdomyolysis
6 month
Frequency of drug discontinuation due to SAMS side effects
Time Frame: 6 month
Frequency of drug discontinuation due to SAMS side effects
6 month
Frequency of drug discontinuation due to side effects other than SAMS
Time Frame: 6 month
Frequency of drug discontinuation due to side effects other than SAMS
6 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Korea University Anam Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 11, 2021

Primary Completion (Actual)

May 14, 2023

Study Completion (Actual)

June 28, 2023

Study Registration Dates

First Submitted

March 25, 2021

First Submitted That Met QC Criteria

March 31, 2021

First Posted (Actual)

April 1, 2021

Study Record Updates

Last Update Posted (Actual)

August 8, 2023

Last Update Submitted That Met QC Criteria

August 6, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SaveSAMS

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Atheroscleroses, Coronary

Clinical Trials on Rosuvastatin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ecuador

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe