Cardiovascular Disease
Conditions
Brief summary
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 strategy (intensive targeting \[LDL-cholesterol goal of \<55mg/dL\] vs. conventional therapy \[moderate intensity statin therapy\]) in elderly patients with ≥75 years and documented cardiovascular disease.
Interventions
DRUGIntensive targeting group
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.
DRUGConventional therapy group
Only moderate intensity statin therapy (atorvastatin 5, 10, and 20mg ) are allowed. Ezetimibe or PCSK-9 inhibitor is not allowed to use.
Sponsors
Yonsei University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
75 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥75 years 2. Documented atherosclerotic 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
1. MI or stroke within 1 year 2. LDL-cholesterol level less than 55 mg/dL without statin therapy 3. Active liver disease or persistent unexplained serum AST/ALT elevation more than 2 times the upper limit of normal range 4. Allergy or hypersensitivity to any statin 5. Life expectancy less than 1 years 6. Inability to follow the patient over the period of 1 year after enrollment, as assessed by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical efficacy of intensive lipid-lowering therapy | 3 years | Primary Outcome - Composite of cardiovascular death, non-fatal myocardial infarction (MI), non-fatal stroke, coronary revascularization, and hospitalization for unstable angina |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular death | 3 years | Occurrence of cardiovascular death during the 3-year follow-up period |
| Non-fatal MI | 3 years | Occurrence of non-fatal MI during the 3-year follow-up period |
| Non-fatal stroke | 3 years | Occurrence of non-fatal stroke during the 3-year follow-up period |
| Coronary revascularization | 3 years | Occurrence of coronary revascularization during the 3-year follow-up period |
| Hospitalization for unstable angina | 3 years | Occurrence of hospitalization for unstable angina during the 3-year follow-up period |
| Composite of cardiovascular death, non-fatal MI, and non-fatal stroke | 3 years | First occurrence of cardiovascular death, non-fatal MI, or non-fatal stroke during the 3-year follow-up period |
| Composite of cardiovascular death, non-fatal MI, non-fatal stroke, and coronary revascularization | 3 years | First occurrence of cardiovascular death, non-fatal MI, non-fatal stroke, or coronary revascularization during the 3-year follow-up period |
| Composite of cardiovascular death, non-fatal MI, and coronary revascularization | 3 years | First occurrence of cardiovascular death, non-fatal MI, or coronary revascularization during the 3-year follow-up period |
| Composite of all-cause death, non-fatal MI, non-fatal stroke, coronary revascularization, and hospitalization for unstable angina | 3 years | First occurrence of all-cause death, non-fatal MI, non-fatal stroke, coronary revascularization, or hospitalization for unstable angina during the 3-year follow-up period |
| Rate of cross-over into the non-allocated therapy strategy | 3 years | Rate of cross-over into the non-allocated therapy strategy at 1 month, and 1, 2, and 3 years after enrollment |
| New-onset diabetes mellitus | 3 years | Occurrence of new-onset diabetes mellitus during the 3-year follow-up period |
| Worsening of glycemic control | 3 years | Occurrence of worsening of glycemic control during the 3-year follow-up period |
| Change of homeostasis model assessment of insulin resistance (HOMA-IR) index | 3 years | Change in HOMA-IR index from baseline at 1, 2, and 3 years after enrollment |
| Occurrence of statin-associated muscle symptoms (SAMS) requiring change of therapy regimen or dosage | 3 years | Occurrence of SAMS requiring change of therapy regimen or dosage during the 3-year follow-up period |
| Elevation of muscle enzymes | 3 years | Occurrence of elevation of muscle enzymes (CPK level \> 4 x UNL) during the 3-year follow-up period |
| Elevation of hepatic enzymes | 3 years | Occurrence of elevation of hepatic enzymes (AST, ALT, or both levels ≥ 3 x UNL) during the 3-year follow-up period |
| Elevation of serum creatinine level | 3 years | Occurrence of elevation of serum creatinine level (\>50% increase from baseline) during the 3-year follow-up period |
| Change of proteinuria | 3 years | Change in proteinuria assessed by urinalysis from baseline at 1, 2, and 3 years after enrollment |
| Diagnosis of cancer | 3 years | Occurrence of diagnosis of cancer during the 3-year follow-up period |
| Operation due to cataract | 3 years | Occurrence of operation due to cataract during the 3-year follow-up period |
| Major bleeding (BARC 2, 3, or 5) | 3 years | Occurrence of major bleeding (BARC 2, 3, or 5) during the 3-year follow-up period |
Countries
South Korea
Outcome results
None listed