Lowering LDL cholesterol in older patients with heart disease

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

This study is testing whether aiming for lower or higher LDL cholesterol levels can help older patients with heart disease stay healthier and avoid serious heart problems.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 4200 (estimated)
• Ages: 75 Years and up
• Sex: All
• Sponsor: China National Center for Cardiovascular Diseases (Government)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT05765370 on ClinicalTrials.gov

What this trial studies

This trial aims to compare the effectiveness and safety of two different LDL cholesterol targets in patients aged 75 and older who have atherosclerotic cardiovascular disease (ASCVD). Participants will be randomly assigned to achieve either a lower LDL-C target of 25 to <70 mg/dL or a higher target of 70 to <100 mg/dL. The study will assess the impact of these targets on major cardiovascular events and potential safety concerns. By focusing on older adults, this trial addresses a significant gap in existing research regarding cholesterol management in this age group.

Who should consider this trial

Good fit: Ideal candidates are men and women aged 75 years or older with a diagnosis of atherosclerotic cardiovascular disease.

Not a fit: Patients without a diagnosis of atherosclerotic cardiovascular disease or those younger than 75 years may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide clearer guidelines for LDL cholesterol management in older patients, potentially reducing cardiovascular events.

How similar studies have performed: While there is limited direct evidence from randomized trials for LDL-C targets in older patients, previous studies have shown benefits of LDL cholesterol lowering in broader populations.

Eligibility criteria

Inclusion Criteria:

1. Men or women ≥75 years of age
2. Diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) with one or more of the following:

   1. Diagnosis of coronary heart disease (one or more of the following criteria must be satisfied):

      * Hospitalization for acute coronary syndrome
      * Treatment or hospitalization for stable angina pectoris with documented ischemia on invasive or noninvasive testing
      * History of myocardial infarction
      * History of coronary revascularization procedure (eg, percutaneous coronary intervention \[PCI\] or coronary artery bypass graft surgery \[CABG\])
      * Invasive diagnostic coronary angiography indicating \>50% stenosis in at least one major epicardial coronary artery or CT-imaging (eg, CCTA/MDCT) evidence of coronary atherosclerosis (\>50% stenosis in at least two major epicardial coronary artery)
   2. Diagnosis of atherosclerotic cerebrovascular or carotid disease (one or more of the following criteria must be satisfied):

      * History of ischemic stroke or transient ischemic attack (TIA) confirmed by symptoms with a documented ischemic lesion on CT or MRI in the cerebral regions corresponding to the symptoms;
      * Documented intracranial atherosclerotic stenosis on the basis of conventional cerebral angiography, magnetic resonance angiography, CT angiography, transcranial doppler ultrasound, and high-resolution MRI;
      * Symptomatic carotid artery disease with ≥50% carotid arterial stenosis;
      * Asymptomatic carotid artery disease with ≥70% carotid arterial stenosis per angiography or duplex ultrasound;
      * History of carotid revascularization (catheter-based or surgical).
   3. Diagnosis of atherosclerotic peripheral artery disease (one or more of the following criteria must be satisfied):

      * History of aorto-iliac or peripheral arterial intervention (catheter-based or surgical).
      * Prior non-traumatic amputation of a lower extremity due to peripheral artery disease
      * History of intermittent claudication and one or more of the following:

        1. An ankle/arm blood pressure (BP) ratio \< 0.90, or
        2. Significant peripheral artery stenosis (≥50%) documented by angiography, or by duplex ultrasound
3. Baseline LDL-C level should be satisfied:

   * Patients were required to have a baseline LDL-C level ≥100mg/dL (2.6mmol/L) if they were taking a regimen of lipid-lowering therapy \<4 weeks or they had not previously received lipid-lowering therapy.
   * Patients were required to have a baseline LDL-C level ≥70mg/dL (1.8mmol/L) if they were on stable treatment with lipid-lowering therapy ≥4 weeks
4. Signed written informed consent.

Exclusion Criteria:

1. Subject was clinically unstable:

   1. Hypotension, defined as sustained systolic blood pressure of \<90 mmHg due to cardiac failure with associated symptoms;
   2. Unstable or severe pulmonary edema/decompensated congestive heart failure;
   3. Acute mitral regurgitation or acute ventricular septal defect;
   4. Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support
   5. Ongoing Non-STEMI with biomarkers (cardiac troponin) still rising
   6. Recent STEMI (≤7 days prior to randomization)
   7. Recurrent symptoms of cardiac ischemia
2. Moderate to severe heart failure (New York Heart Association \[NYHA\] Functional Classification III or IV) or last known left ventricular ejection farction (LVEF) \<40%.
3. Severe renal dysfunction, defined as creatinine clearance \<30 mL/min or estimated glomerular filtration (eGFR) rate less than 30 ml/min/1.73 m2, or requirement for peritoneal dialysis or hemodialysis for renal insufficiency.
4. History of hemorrhagic stroke or unknown classified stroke.
5. Uncontrolled or recurrent ventricular tachycardia (such as ventricular fibrillation, recurrent and highly symptomatic ventricular tachycardia, complete heart block, atrial fibrillation with rapid ventricular response, or supraventricular tachycardia that are not controlled by medications).
6. Uncontrolled hypertension (greater than 180 mm Hg systolic and/or greater than 110 mm Hg diastolic at randomization visit).
7. History or clinical evidence of active liver disease or hepatic dysfunction, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × upper limit of normal (ULN), or total bilirubin \> 2 × ULN.
8. Unexplained elevated creatine kinase (CK) concentration \>5 × ULN or elevation due to known muscle disease.
9. Planned or expected cardiac surgery, PCI or carotid stenting, or planned major noncardiac surgery during the study period. If angiography or revascularization is planned, patients may be screened and enrolled after all such planned procedures are completed.
10. Active Malignancy (except nonmelanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ, or stage 1 prostate carcinoma) including those patients requiring surgery, chemotherapy, and/or radiation in the past 3 years.
11. Drug or alcohol abuse, and inability/unwillingness to abstain from drug abuse and excessive alcohol consumption during the study.
12. Severe, concomitant noncardiovascular disease that is expected to reduce life expectancy to \<3 years
13. Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies), or receiving other investigational agent(s)
14. Subject has received drugs via a systemic route that have known major interactions with background statin therapy (eg, itraconazole, ketoconazole, and other antifungal azoles, erythromycin, clarithromycin, or cyclosporine nefazodone) within 1 month prior to randomization or is likely to require such treatment during the study period.
15. Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal)
16. Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator's knowledge.
17. Any uncontrolled or serious disease, or any medical or surgical condition (such as known active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction, or a chronic disease or infection \[eg, HIV\]), that may either interfere with participation in the clinical study and is not currently stable and appropriately managed in the judgment of the investigator, and/or put the subject at significant risk (according to investigator's judgment) if he/she participates in the clinical study.
18. Mental/psychological impairment/neurocognitive disorder, or any other reason to expect patient difficulty in complying with the requirements of the study or understanding the goal and potential risks of participating in the study

Where this trial is running

Beijing, Beijing Municipality

• Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Principal investigator: Kefei Dou, MD, PhD — Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing
• Study coordinator: Kefei Dou, MD, PhD

Conditions Atherosclerotic Cardiovascular Disease; Older Patients; LDL Cholesterol; LDL-C target; Older patients; Age≥75 years; Lipid-lowering therapy; Stain