Please select the eligibility criteria that correspond to the clinical trial below.
Title: Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Subjects With Heterozygous Familial Hypercholesterolemia (The ENHANCE Trial)
Brief Summary: The purpose of the study is to determine whether ezetimibe plus simvastatin will be more effective than simvastatin alone in preventing progression of atherosclerosis of the inner layer of the carotid artery.


Options:
A: Inclusion Criteria:

* Must be treated with atorvastatin 40 mg/day for at least 30 days prior to screening
* Have an LDL-C \>70 mg/deciliter(dL) or non-HDL-C \>100 mg/dL
* Have screening triglycerides ≤400 mg/dL (≤4.5 millimoles/Liter)
* Individuals with ASCVD and/or individuals with type 1 or type 2 diabetes

Exclusion Criteria:

* Have a hemoglobin A1c (HbA1c) \>9.5%
* New York Heart Association (NYHA) class III or IV congestive heart failure
* History of either a transient ischemic stroke or ischemic stroke \<30 days
* History of acute coronary syndrome (ACS) \<30 days
B: Inclusion Criteria:

* Symptoms consistent with calf claudication and described as life style limiting
* Objective evidence of peripheral artery disease (PAD): Ankle brachial index less than 0.9 OR other hemodynamic or imaging modalities confirming significant PAD
* Baseline imaging reveals superficial femoral artery (SFA) disease starting at least 5 cm from the origin of the SFA
* Agrees to be available for follow-up and is able to participate in all study testing procedures
* Weight and/or body characteristics that will allow testing with MRI
* No known contraindication to lipid lowering agents
* Serum creatinine level less than 2.5 mg/dL
* Scheduled to undergo or has already undergone an endovascular intervention of a de novo lesion in the SFA with an anticipated result that would satisfy hemodynamic stability OR is medically managed and does not require an intervention at this time
* Compressible arteries (if not, has toe brachial index \[TBI\] less than 0.7)
* Has/had an A, B, C lesion amendable to a catheter based therapy (prior bypass is acceptable)

Exclusion Criteria:

* Non-atherosclerotic disease that is responsible for claudication
* Unstable cardiac disease (e.g., unstable angina, heart attack within the 30 days before study entry, uncontrolled coronary heart failure, poorly controlled hypertension \[systolic blood pressure greater than 180 mmHg and/or diastolic blood pressure greater than 100 mmHg\], ventricular arrhythmias)
* Pancreatitis
* Documented hypercoagulable state
* Clinically severe diabetic neuropathy
* Rest pain, gangrene, or tissue loss
* Active peptic ulcer disease or a recent gastrointestinal bleed that would prohibit the use of an anti-platelet (aspirin/Plavix)
* Untreated or unsuccessfully controlled psychiatric disease
* Chronic hepatic disease determined by aspartate transaminase (AST) and/or alanine transaminase (ALT) more than 3 times upper limit of normal (ULN) and/or total bilirubin more than 2 times ULN
* Creatine phosphokinase (CPK) more than 3 times ULN (may be repeated once before patient is excluded)
* Active gout symptoms or a uric acid level greater than 1.3 times ULN
* Untreated hypothyroidism
* Allergy to Plavix, nickel, titanium, niacin, Ezetimibe, statins, or their derivatives
* Participated in another interventional study within the 30 days before study entry
* Scheduled to undergo planned synchronous bilateral percutaneous transluminal angioplasty (PTA) procedures
* Requires an above the ankle amputation
* Scheduled to undergo elective surgery within 30 days after the PTA procedure
* Has an implanted pacemaker, defibrillator, neural stimulator, brain clip, insulin pump, cochlear implant, or any other predetermined radiographic finding that would exclude MRI testing
* Has claustrophobia that would prevent MRI testing
* Recent drug or alcohol abuse history (less than 6 months before study entry) or is currently using or abusing excessive alcohol or drugs (excessive alcohol will be defined as greater than 14 drinks per week)
* Past recipient of a cardiac, kidney, liver, lung, or other organ transplant (skin grafts are acceptable)
C: Inclusion Criteria:

* Genotype-confirmed heterozygous familial hypercholesterolemia with written documentation of the genetic diagnosis at the time of screening and LDL-C \>=210 mg/dL (5.43 mmol/L), or clinical diagnosis of heterozygous familial hypercholesterolemia, defined as LDL-C \>=210 mg/dL (5.43 mmol/L) and at least one of the following:

  * tendinous xanthoma
  * child \<18 years of age with hypercholesterolemia (LDL-C \>159 mg/dL (4.11 mmol/L)
  * has a sibling with hypercholesterolemia (LDL-C \>190 mg/dL \[4.91 mmol/L\]) and tendinous xanthoma
  * family history with an LDL-C value distribution pattern compatible with dominant autosomal transmission and at least one relative presenting fasting total cholesterol values \>348 mg/dL (9.0 mmol/L) after exclusion of secondary causes of dyslipidemia
* LDL-C \>=210 mg/dL (5.43 mmol/L) 1 week before randomization
* plasma triglyceride level \<=400 mg/dL (4.52 mmol/L)

Exclusion Criteria:

* pregnancy or any other situation, condition, or illness that, in the opinion of the investigator, may interfere with optimal participation in the study
* presence of an apolipoprotein B gene mutation with confirmed absence of an LDL receptor mutation in either allele
* undergoing LDL-apheresis or plasma apheresis
* unsuitable plaque or artery morphology
* use of certain drugs, foods, or other agents known to alter cholesterol levels or to cause pharmacokinetic interactions with either ezetimibe or simvastatin
D: 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

Answer: C