Moderate-intensity Statin vs. Individualized LDL-C Target-based Therapy in Older Adults With Type 2 Diabetes (iTARGET-Elderly Study)

Official title

A Registry-based Randomized Controlled Trial of Moderate-intensity Statin Therapy vs. Individualized Low-density Lipoprotein Cholesterol Target-based Therapy for Primary Prevention of Cardiovascular Events in Patients 70 Years of Age or Older With Type 2 Diabetes (iTARGET-Elderly Study)

Overview

Statins are the cornerstone of cardiovascular disease (CVD) prevention through the lowering of low-density lipoprotein cholesterol (LDL-C). While the benefits of intensive LDL-C lowering are well-established for secondary prevention, evidence remains insufficient for primary prevention in the elderly-specifically for individuals aged 70 years or older with type 2 diabetes who have no prior history of atherosclerotic cardiovascular events. Current guidelines generally recommend moderate-intensity statins for this population based on extrapolated data. However, there is a significant evidence gap regarding whether these older adults, who have not yet experienced a cardiovascular event, derive the same risk-benefit ratio from pharmacological intervention as younger or secondary prevention groups. Furthermore, while ezetimibe (alone or in combination) is an effective alternative for patients with established disease, its efficacy as a primary prevention strategy in older diabetic patients has not been rigorously confirmed through randomized controlled trials (RCTs). Therefore, this study specifically focuses on the primary prevention setting, aiming to determine whether individualized LDL-C target-based therapy is non-inferior to standard moderate-intensity statin therapy in preventing first-time cardiovascular events among older patients with type 2 diabetes.

Interventions

• Drug Moderate-intensity statin monotherapy
  Atorvastatin 10 mg, 20 mg, or 40 mg, or rosuvastatin 5 mg, 10 mg, or 20 mg will be administered for up to 3 years. If the LDL-C is ≥100 mg/dL, the investigator may adjust the statin intensity based on the patient's health status.
• Drug Ezetimibe or ezetimibe-statin combination therapy
  Treatment will consist of non-pharmacological interventions or marketed medications, including low-dose statins (atorvastatin 5 mg or 10 mg, rosuvastatin 2.5 mg or 5 mg) in combination with ezetimibe 10 mg, or fixed-dose combinations (rosuvamibe 10/2.5 mg, atorvabmibe 10/5 mg, or Rosuzet 10/2.5 mg), for up to 3 years. If the pre-specified LDL-C target is not achieved or drug intolerance occurs, adjustments in dosage or medication will be made.

Primary outcome measures

• Time from the date of randomization to the first occurrence of a major adverse cardiovascular event (MACE) [Time frame: 0, 3, 12, 24, 36 months]

Secondary outcome measures (7)

• Time from the date of randomization to the first hospitalization due to the following events or to the first occurrence of such events, whichever occurs earlier : (1) ischemic heart disease, (2) cerebrovascular disease, (3) heart failure, (4) peripheral [Time frame: 0, 3, 12, 24, 36 months]
• Time from the date of randomization to the first occurrence of all-cause hospitalization or all-cause death, whichever occurs first [Time frame: 0, 3, 12, 24, 36 months]
• Serum lipid levels from baseline at each assessment time point [Time frame: 0, 3, 12, 24, 36 months]
• Serum lipid changes from baseline at each assessment time point [Time frame: 0, 3, 12, 24, 36 months]
• Patterns of study drug use [Time frame: From baseline up to 36 months]
• Incidence rates and characteristics of adverse events, adverse drug reactions, and serious adverse events [Time frame: From baseline up to 36 months]
• Incidence rates and characteristics of adverse events of special interest (AESI) [Time frame: From baseline up to 36 months]

Eligibility criteria

Inclusion criteria

• Provision of written informed consent to participate in the study by the patient or his/her legally authorized representative after receiving and understanding a detailed explanation of the study
• Adults aged 70 years or older
• Diagnosed with type 2 diabetes or currently receiving antidiabetic medication, without a history or presence of cardiovascular disease
• Either: (1) LDL-C≥100 mg/dL if not receiving lipid-lowering therapy, or (2) currently receiving lipid-lowering therapy (in this case, LDL-C level not restricted)

Exclusion criteria

• Diagnosis of type 1 diabetes
• Documented history of atherosclerotic cardiovascular disease at screening, confirmed clinically or by imaging: (1) myocardial infarction; (2) coronary revascularization; (3) currently receiving treatment for acute coronary syndrome; (4) history of ischemic stroke; (5) aortic aneurysm; (6) peripheral arterial disease
• Currently undergoing cancer treatment
• Severe disease requiring recurrent hospitalization
• Frailty (defined as a score ≥3 on the Korean FRAIL questionnaire), or any condition significantly limiting self-care
• AST or ALT >3 × ULN, at screening (however, patients will be eligible if repeat testing at the time of randomization shows levels <3 × ULN), or liver cirrhosis
• Contraindications to study drugs
• Pregnant or breastfeeding women

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Prevention

Study locations

South Korea · 2 centers

• Korea University ANAM Hospital — Seoul
• Severance Hospital — Seoul

Identifiers

NCT: NCT07359105 · 2025AN0165

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗