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

Inclusion Criteria:

1. Men or women ≥75 years of age
2. Diagnosis of clinical atherosclerotic cardiovascular disease (ASCVD) with one or moreof the following:
3. Diagnosis of coronary heart disease (one or more of the following criteria mustbe satisfied):

• Hospitalization for acute coronary syndrome
• Treatment or hospitalization for stable angina pectoris with documentedischemia on invasive or noninvasive testing
• History of myocardial infarction
• History of coronary revascularization procedure (eg, percutaneous coronaryintervention [PCI] or coronary artery bypass graft surgery [CABG])
• Invasive diagnostic coronary angiography indicating >50% stenosis in atleast one major epicardial coronary artery or CT-imaging (eg, CCTA/MDCT)evidence of coronary atherosclerosis (>50% stenosis in at least two majorepicardial coronary artery)

2. Diagnosis of atherosclerotic cerebrovascular or carotid disease (one or more ofthe following criteria must be satisfied):

• History of ischemic stroke or transient ischemic attack (TIA) confirmed bysymptoms with a documented ischemic lesion on CT or MRI in the cerebralregions corresponding to the symptoms;
• Documented intracranial atherosclerotic stenosis on the basis ofconventional cerebral angiography, magnetic resonance angiography, CTangiography, 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 perangiography or duplex ultrasound;
• History of carotid revascularization (catheter-based or surgical).

3. Diagnosis of atherosclerotic peripheral artery disease (one or more of thefollowing criteria must be satisfied):

• History of aorto-iliac or peripheral arterial intervention (catheter-basedor surgical).
• Prior non-traumatic amputation of a lower extremity due to peripheral arterydisease
• 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 byangiography, 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) ifthey were taking a regimen of lipid-lowering therapy <4 weeks or they had notpreviously received lipid-lowering therapy.
• Patients were required to have a baseline LDL-C level ≥70mg/dL (1.8mmol/L) ifthey were on stable treatment with lipid-lowering therapy ≥4 weeks

4. Signed written informed consent.

Exclusion Criteria:

1. Subject was clinically unstable:
2. Hypotension, defined as sustained systolic blood pressure of <90 mmHg due tocardiac failure with associated symptoms;
3. Unstable or severe pulmonary edema/decompensated congestive heart failure;
4. Acute mitral regurgitation or acute ventricular septal defect;
5. Cardiogenic shock and/or need for mechanical/pharmacologic hemodynamic support
6. Ongoing Non-STEMI with biomarkers (cardiac troponin) still rising
7. Recent STEMI (≤7 days prior to randomization)
8. Recurrent symptoms of cardiac ischemia
9. Moderate to severe heart failure (New York Heart Association [NYHA] FunctionalClassification III or IV) or last known left ventricular ejection farction (LVEF) <40%.
10. Severe renal dysfunction, defined as creatinine clearance <30 mL/min or estimatedglomerular filtration (eGFR) rate less than 30 ml/min/1.73 m2, or requirement forperitoneal dialysis or hemodialysis for renal insufficiency.
11. History of hemorrhagic stroke or unknown classified stroke.
12. 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 arenot controlled by medications).
13. Uncontrolled hypertension (greater than 180 mm Hg systolic and/or greater than 110 mmHg diastolic at randomization visit).
14. History or clinical evidence of active liver disease or hepatic dysfunction, defined asalanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 × upper limitof normal (ULN), or total bilirubin > 2 × ULN.
15. Unexplained elevated creatine kinase (CK) concentration >5 × ULN or elevation due toknown muscle disease.
16. Planned or expected cardiac surgery, PCI or carotid stenting, or planned majornoncardiac surgery during the study period. If angiography or revascularization isplanned, patients may be screened and enrolled after all such planned procedures arecompleted.
17. Active Malignancy (except nonmelanoma skin cancers, cervical in-situ carcinoma, breastductal carcinoma in situ, or stage 1 prostate carcinoma) including those patientsrequiring surgery, chemotherapy, and/or radiation in the past 3 years.
18. Drug or alcohol abuse, and inability/unwillingness to abstain from drug abuse andexcessive alcohol consumption during the study.
19. Severe, concomitant noncardiovascular disease that is expected to reduce lifeexpectancy to <3 years
20. Currently receiving treatment in another investigational device or drug study, or lessthan 30 days since ending treatment on another investigational device or drugstudy(ies), or receiving other investigational agent(s)
21. Subject has received drugs via a systemic route that have known major interactionswith background statin therapy (eg, itraconazole, ketoconazole, and other antifungalazoles, erythromycin, clarithromycin, or cyclosporine nefazodone) within 1 month priorto randomization or is likely to require such treatment during the study period.
22. Recipient of any major organ transplant (eg, lung, liver, heart, bone marrow, renal)
23. Subject likely to not be available to complete all protocol-required study visits orprocedures, and/or to comply with all required study procedures (eg, Clinical OutcomeAssessments) to the best of the subject and investigator's knowledge.
24. Any uncontrolled or serious disease, or any medical or surgical condition (such asknown active infection or major hematologic, renal, metabolic, gastrointestinal orendocrine dysfunction, or a chronic disease or infection [eg, HIV]), that may eitherinterfere with participation in the clinical study and is not currently stable andappropriately managed in the judgment of the investigator, and/or put the subject atsignificant risk (according to investigator's judgment) if he/she participates in theclinical study.
25. Mental/psychological impairment/neurocognitive disorder, or any other reason to expectpatient difficulty in complying with the requirements of the study or understandingthe goal and potential risks of participating in the study