Table 1.
Eligibility Criteria
| Inclusion Criteria |
|---|
| Age 18–80 years, inclusive |
| Not taking a statin or on a low‐dose statin, defined as a maximum weekly dose of: |
| ≤70 mg atorvastatin |
| ≤140 mg simvastatin, pravastatin, or lovastatin |
| ≤35 mg rosuvastatin |
| ≤280 mg fluvastatin |
| Not at LDL‐C goal per NCEP‐ATP III risk categories for fasting LDL‐C: |
| ≥100 mg/dL (2.6 mmol/L) for subjects who had CHD or CHD risk equivalent |
| ≥130 mg/dL (3.4 mmol/L) for subjects who did not have diagnosed CHD or risk equivalent but had ≥2 risk factors |
| ≥160 mg/dL (4.1 mmol/L) for subjects who did not have diagnosed CHD or risk equivalent but had 1 risk factor |
| ≥190 mg/dL (4.1 mmol/L) for subjects who did not have diagnosed CHD or risk equivalent and had no risk factors |
| History of statin intolerance, demonstrated by both: |
| Trial of ≥2 statins with intolerance of any dose or to increase statin dose above the total maximum doses because of intolerable: |
| Myopathy or myalgia (muscle pain, ache, or weakness without CK elevation), or |
| Myositis (muscle symptoms with increased CK levels), or |
| Rhabdomyolysis (muscle symptoms with marked CK elevation) and |
| Resolution or improvement of symptoms when the statin dose was decreased or discontinued |
| Stable doses of lipid‐lowering therapies including statins, bile‐acid sequestrants, or stanols for ≥4 weeks before LDL‐C screening |
| Discontinuation of ezetimibe for a washout period of ≥4 weeks before LDL screening |
| Fasting triglyceride level ≤400 mg/dL (4.5 mmol/L) by central laboratory at screening |
| Key Exclusion Criteria |
| Cardiovascular |
| NYHA class III–IV heart failure or last known LVEF <30% |
| Uncontrolled serious cardiac arrhythmia, defined as recurrent and highly symptomatic VT, AF with rapid ventricular response, or SVT that are not controlled by medications, within 3 months prior to randomization |
| MI, UA, PCI, CABG, or stroke within 3 months prior to randomization |
| Planned cardiac surgery or revascularization |
| DM, including: |
| Type 1 DM |
| Type 2 DM that is poorly controlled (HbA1c >8.5%) or newly diagnosed within 6 months before randomization |
| Laboratory evidence of DM during screening (fasting serum glucose ≥126 mg/dL [7.0 mmol/L] or HbA1c ≥6.5%) without prior DM diagnosis |
| Uncontrolled hypertension, defined as sitting SBP >160 mm Hg or DBP >100 mm Hg |
| Medications |
| Use during the 6 months before LDL‐C screening of red yeast rice, niacin >200 mg/d, prescription lipid‐regulating drugs (eg, fibrates or derivatives) other than statins, ezetimibe, bile‐acid sequestrants, stanols, or stanol esters |
| Use during the 12 months before LDL‐C screening of a CETP inhibitor such as anacetrapib, dalcetrapib, or evacetrapib |
| Use during the 3 months before LDL‐C screening of systemic cyclosporine, systemic steroids excluding HRT, vitamin A derivatives (excluding vitamin A in a multivitamin), or retinol derivatives for the treatment of dermatologic conditions |
| Key Exclusion Criteria |
|---|
| Laboratory values at screening |
| TSH < LLN or >1.5 × ULN |
| eGFR <30 mL/min/1.73 m2 |
| CK >3 × ULN |
| AST or ALT >2 × ULN |
| Known concurrent illness within 3 months |
| Infection |
| Major hematologic, renal, metabolic, GI, or endocrine dysfunction in the judgment of the investigator |
| DVT or PE |
| Other |
| Pregnancy, breastfeeding, or inadequate birth control in premenopausal female subjects |
| Previous treatment with evolocumab or any other anti‐PCSK9 therapy |
| Inability to provide informed consent or to attend follow‐up visits |
| Unreliability as a study participant based on judgment of investigator's knowledge of the subject (eg, alcohol or other drug abuse, inability or unwillingness to adhere to the protocol, psychosis) |
| Current enrollment in another investigational device or drug study or <30 d since ending another investigational device or drug study |
Abbreviations: AF, atrial fibrillation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CABG, coronary artery bypass grafting; CHD, coronary heart disease; CK, creatine kinase; CETP, cholesterylester transfer protein; DBP, diastolic blood pressure; DM, diabetes mellitus; DVT, deep‐vein thrombosis; eGFR, estimated glomerular filtration rate; GI, gastrointestinal; HbA1c, glycated hemoglobin; HRT, hormone replacement therapy; LDL‐C, low‐density lipoprotein cholesterol; LLN, lower limit of normal; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NCEP‐ATP III, National Cholesterol Education Program Adult Treatment Panel III; NYHA, New York Heart Association; PCI, percutaneous coronary intervention; PCSK9, proprotein convertase subtilisin/kexin type 9; PE, pulmonary embolism; SBP, systolic blood pressure; SVT, supraventricular tachycardia; TSH, thyroid‐stimulating hormone; UA, unstable angina; ULN, upper limit of normal; VT, ventricular tachycardia.