Effect of Intensive LDL-cholesterol Targeting for Elderly Patients With Cardiovascular Disease: I-OLD Trial

Study Overview
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Brief Summary
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Although there have been studies regarding intensive lowering of low-density lipoprotein (LDL)-cholesterol with high intensity statins in patients with cardiovascular disease, elderly patients were either excluded or accounted only a small portion of study subjects. Therefore, this study sought to compare the clinical outcomes according to the LDL-cholesterol therapy targeting (intensive targeting [LDL-cholesterol <55mg/dL] vs. conventional therapy [moderate intensity statin therapy]) in elderly patients with ≥75 years and documented cardiovascular disease.

Official Title
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Effect of Intensive LDL-cholesterol Targeting for Elderly Patients With Cardiovascular Disease: I-OLD Trial

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Drug: Intensive targeting group
* Drug: Conventional therapy group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥75 years Documented cardiovascular disease (at least 1 of the following) A. Previous acute coronary syndrome (MI or unstable angina) B. Or stable angina with imaging studies of coronary artery disease or functional studies of myocardial ischemia C. Or coronary revascularization (percutaneous coronary intervention or coronary artery bypass graft) D. Or peripheral artery disease. Exclusion Criteria: MI or stroke within 1 year LDL-cholesterol level less than 55 mg/dL without statin therapy Active liver disease or persistent unexplained serum AST/ALT elevation more than 2 times the upper limit of normal range Allergy or hypersensitivity to any statin Life expectancy less than 1 years Inability to follow the patient over the period of 1 year after enrollment, as assessed by the investigator

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive targeting group<br>Intensive lipid loweroing therapy with LDL-cholesterol goal of <55mg/dL | Drug: Intensive targeting group<br>* Intensive lipid lowering therapy with LDL-cholesterol goal of <55mg/dL. Atorvastatin 5, 10, 20, 40, and 80mg are allowed to use and ezetimibe or PCSK-9 inhibitor may be considered in patients who could not achieve target LDL-cholesterol level even with the maximum dose of study drugs (atorvastatin 80mg) by the discretion of the investigator.<br>|
| Active Comparator: Conventional therapy group<br>Initiate and maintain moderate intensity statin therapy | Drug: Conventional therapy group<br>* Only moderate intensity statin therapy (atorvastatin 5, 10, and 20mg ) are allowed. Ezetimibe or PCSK-9 inhibitor is not allowed to use.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical efficacy of intensive lipid-lowering therapy | Composite of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, coronary revascularization, and hospitalization for angina | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy endpoint | Each component of primary endpoint Various composite outcomes A. Composite of cardiovascular death, non-fatal MI, and non-fatal stroke B. Composite of cardiovascular death, non-fatal MI, non-fatal stroke, and coronary revascularization C. Composite of cardiovascular death, non-fatal MI, and coronary revascularization D. Composite of all-cause death, non-fatal MI, non-fatal stroke, coronary revascularization, and hospitalization for angina Rate of cross-over into the non-allocated therapy regimen (1, 2, and 3 years after enrollment) | 3 years | 
| Safety endpoint | New-onset diabetes mellitus, worsening of glycemic control, or homeostatic model assessment (HOMA)-index Occurrence of statin-associated muscle symptoms (SAMS) requiring change of therapy regimen or dosage Elevation of muscle enzymes (CPK > 4 x UNL) Elevation of hepatic enzymes (AST, ALT, or both ≥ 3 x UNL) Elevation of serum creatinine level (>50% from baseline) Change of proteinuria Diagnosis of cancer Operation due to cataract Major bleeding (BARC 2, 3, or 5) | 3 years |