Effects of Statin for Elderly Patients With Atherosclerotic Cardiovascular Disease

NCT04826354 | Completed Phase 4 FDA Drug

• 1 other identifier: SaveSAMS
• Study Type: interventional
• Target: 582
• Locations: 1 country
• Sites: 2

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.

Conditions

Atheroscleroses, Coronary

Keywords

Elderly; Statin; Ezetimibe

Outcome Measures

Primary Outcomes (2)

• Statin-Associated Muscle Symptoms (SAMS)

  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

  Target LDL-C achievement (LDL \<70mg/dL)

  6 month

Secondary Outcomes (9)

• CK levels

  6 month

• GOT levels

  6 month

• GPT levels

  6 month

• Levels of Total cholesterol, LDL cholesterol, HDL cholesterol

  6 month

• Level of Triglyceride

  6 month

Study Arms (2)

Rosuvastatin

EXPERIMENTAL

Rosuvastatin 20mg

Drug: Rosuvastatin

Rosuvamibe

ACTIVE COMPARATOR

Rosuvastatin plus ezetimibe 10/5

Drug: Rosuvastatin and Ezetimibe

Interventions

Rosuvastatin and Ezetimibe DRUG

Rosuvastatin Versus Rosuvastatin plus Ezetimibe

Rosuvamibe

Rosuvastatin DRUG

Rosuvastatin

Rosuvastatin

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Those who are 70 years of age or older as of the date of consent
• Established arteriosclerotic cardiovascular disease (coronary artery disease, cerebrovascular disease, or peripheral vascular disease)
• 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

You may not qualify if:

• Take statins or ezetimibe within the last 4 weeks
• In case of end-stage kidney disease (eGFR\<30 ml/min/1.73m2)
• Heart surgery or major surgery is planned within the next 6 months
• Patients with chronic diseases such as severe lung disease, stroke, etc.
• Patients with chronic inflammatory diseases who require oral, intravenous, or intra-articular steroid treatment (Ointments, inhalants, or intranasal steroids are allowed)
• If you have been diagnosed with cancer within the past 1 year or are currently receiving chemotherapy
• 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
• Liver disease, bile duct obstruction, or liver enzyme level (ALT/AST) is more than 3 times normal
• If you have a disease whose life expectancy is less than 1 year
• If you do not want or cannot comply with the procedure described in the research proposal

Sponsors & Collaborators

• Korea University Anam Hospital: lead

Study Sites (2)

Kangbuk Samsung Hospital

Seoul, South Korea

Location

Korea University Anam Hospital

Seoul, South Korea

Location

Related Publications (26)

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MeSH Terms

Conditions

Coronary Artery Disease

Interventions

Rosuvastatin Calcium; Ezetimibe

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azetidines; Azetines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Effects of high-dose Statin Versus low-dose statin plus ezetimibe on statin-associated Muscle Symptoms

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 1, 2021
• Study Start: August 11, 2021
• Primary Completion: May 14, 2023
• Study Completion: June 28, 2023
• Last Updated: August 8, 2023

Record last verified: 2023-08

Locations

KR (2)