LDL Cholesterol TARGETs in OLDer Patients (Age≥75 Years) With ASCVD (TARGET OLD)

Atherosclerotic Cardiovascular Disease Clinical Trial

Official title: LDL Cholesterol TARGETs in OLDer Patients (Age≥75 Years) With Atherosclerotic Cardiovascular Disease (TARGET OLD)

Status Recruiting

Clinical Trial Summary

To determine whether treating to an LDL-C target of 25 to <70 mg/dL is superior to an LDL-C target of 70 to <100 mg/dL with respect to major cardiovascular events (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization) in patients aged ≥75 years with atherosclerotic cardiovascular disease (ASCVD).

To determine whether treating to an LDL-C target of 25 to <70 mg/dL is non-inferior to an LDL-C target of 70 to <100 mg/dL with respect to major safety events (hemorrhagic stroke, new-onset diabetes, muscle-related events, neurocognitive adverse events, new or recurrent cancer, cataract, or hepatic disorder [Alanine aminotransferase (ALT)/Aspartate aminotransferase (AST) >3× ULN, or total bilirubin >2× ULN]) in patients aged ≥75 years with ASCVD.

Clinical Trial Description

The benefits of LDL cholesterol-lowering treatment for the prevention of atherosclerotic cardiovascular disease (ASCVD) are well established. LDL-C lowering is associated with a significant reduction in major adverse cardiovascular events in a linear fashion, apparently without any plateau at low LDL-C levels. On the other hand, the degree to which LDL-C levels can be safely lowered remains unclear. It is still controversial whether lower LDL-C levels are associated with significant clinical adverse effects (e.g. new-onset diabetes mellitus or possibly hemorrhagic stroke) and long-term data are needed to address safety concerns.

It should be noted that the benefits and risks from LDL cholesterol lowering in older patients (age ≥75 years) remains debated because most randomized trials have explicitly excluded or enrolled few older adults. In clinical practice, the appropriate treatment target for LDL-C in patients ≥75 years of age with ASCVD remains uncertain. Current US and European cholesterol guidelines have no specific recommendations regarding the LDL-C treatment goal for older patients and noted that the level of evidence in older patients is low. Currently, there is no direct evidence from randomized clinical trials (RCTs) for the most appropriate treatment targets for LDL-C among patients ≥75 years of age with ASCVD in worldwide.

The TARGET OLD trial is a multicenter, open-label, parallel-group, event-driven, randomized, controlled trial with blinded end-point evaluation. Consecutive patients aged ≥75 years with ASCVD who meet the inclusion criteria and none of the exclusion criteria outlined above will be randomized in a 1:1 fashion to LDL-C target of 25 to <70 mg/dL or LDL-C target of 70 to <100 mg/dL. The proposed study will examine the comparative efficacy and safety of treating to an LDL-C target of 25 to <70 mg/dL compared with an LDL-C target of 70 to <100 mg/dL among patients aged 75 years or older with ASCVD. Our primary hypothesis is that, among such patients, targeting an LDL-C of 25 to less than 70 mg/dL is superior to a target of 70 to less than 100 mg/dL on reducing the risk of major adverse cardiovascular events (primary efficacy end point), while is non-inferior towards the composite of major safety outcomes (key secondary safety end point).

Prescription of lipid-lowering agents (drug and dosage up to the investigator according to the assigned target LDL-C level. Statin monotherapy or in combination with ezetimibe, PCSK9 inhibitor or other drugs were adjusted on the basis of the study-group assignment. Patients will follow-up at 1, 2, 4, 6, 12 months, and then every 6 months throughout 36 months with an evaluation of patients' lipid profiles, any cardiovascular events, safety and adverse events, muscle-related symptoms, quality of life (EQ-5D), and patient-reported cognition function (ECog scale). The trial will continue until 726 adjudicated primary endpoint events have occurred. We estimated that 4,200 patients would be needed to provide the necessary number of confirmed endpoints to test the study hypothesis. All analyses will be according to the intention-to-treat (ITT) principle. ;

Related Conditions & MeSH terms

• Atherosclerosis
• Atherosclerotic Cardiovascular Disease
• Cardiovascular Diseases
• LDL Cholesterol
• Older Patients

• NCT number: NCT05765370
• Study type: Interventional
• Source: China National Center for Cardiovascular Diseases
• Contact: Kefei Dou, MD, PhD
• Phone: +86-10-13801032912
• Email: drdoukefei@126.com
• Status: Recruiting
• Phase: N/A
• Start date: March 24, 2023
• Completion date: December 24, 2026