Durable Effect of PCSK9 Antibody CompARed wiTh placEbo Study

Eligible participants with screening central laboratory low-density lipoprotein cholesterol (LDL-C) values ≥ 75 mg/dL (1.9 mmol/L) were instructed to follow National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP) Therapeutic Lifestyle Changes (TLC) diet and were assigned to 1 of the following 4 background lipid-lowering therapies for a 4-week stabilization period based upon their screening LDL-C and its distance from the individual's required goal as stipulated by their NCEP ATP III risk category:

• no drug therapy required - diet alone
• low dose drug therapy required - diet plus atorvastatin 10 mg orally (PO) once daily (QD)
• high dose drug therapy required - diet plus atorvastatin 80 mg PO QD
• maximal drug therapy required - diet plus atorvastatin 80 mg PO QD plus ezetimibe 10 mg PO QD.

If the participant met entry criteria at the end of the lipid stabilization period they were randomized 2:1 to receive evolocumab 420 mg or placebo subcutaneously once a month for 52 weeks in addition to their background therapy.

Inclusion criteria

• Subject has provided informed consent.
• Fasting LDL-C ≥ 75 mg/dL and meeting the following LDL-C values on background lipid-lowering therapy:

• < 100 mg/dL for subjects with diagnosed coronary heart disease (CHD) or CHD risk equivalent
• < 130 mg/dL for subjects without diagnosed CHD or CHD risk equivalent
• OR on maximal background lipid-lowering therapy defined as atorvastatin 80 mg PO QD and ezetimibe 10 mg PO QD
• Fasting triglycerides ≤ 400 mg/dL

Exclusion criteria

• New York Heart Association (NYHA) II-IV heart failure, or last known left ventricular ejection fraction < 30%
• Uncontrolled cardiac arrhythmia
• Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months prior to randomization, type 1 diabetes, newly diagnosed or poorly controlled type 2 diabetes
• Uncontrolled hypertension