Study Design

Study Design:

Patients Screened: 64
Patients Enrolled: 40
Mean Follow Up: 12 weeks
Mean Patient Age: 67.6 years
Female: 10

Patient Populations:

• Age 19-79 years
• Female patients had to be of nonchildbearing potential
• Carotid stenosis >40% on duplex ultrasonography
• Intraplaque accumulation of USPIO on MRI at baseline
• Positive USPIO-enhanced MRI of carotid plaque confirmed by an attending neuroradiologist
• Statin naïve or on a stable dose of a statin for ≥4 weeks before screening, with no evidence of statin intolerance

Exclusions:

• <10% signal drop in two or more quadrants on T2*-weighted imaging sequences
• Required continued use of nonstatin lipid-modifying therapies (e.g., fibric acid derivatives, niacin, resins, ezetimibe, fish-oil supplement) or therapy with any other lipid-regulating medications not specified (dietary supplements or multivitamins containing a daily dose of niacin 250 mg were allowed)
• History of statin intolerance
• History of chronic viral hepatitis or other chronic hepatic disorders, or alanine aminotransferase or aspartate aminotransferase >1.5 times the upper limit of normal, or alkaline phosphatase or total bilirubin >1.5 times the upper limit of normal of laboratory reference range at screening
• Creatinine clearance <50 ml/min
• History of myopathy or inflammatory muscle disease, or elevated total serum creatine kinase (3 times upper limit of normal) at screening visit
• Doppler assessment of <40% stenosis or carotid occlusion during screening assessment
• History of clinically significant atopy (e.g., anaphylaxis, skin rash to medication or topical therapies, hypersensitivity to iodinated contrast media, allergies to food such as shellfish, bronchial asthma) and allergies to dextran and iron salts
• Clinical contraindications to MRI including but not limited to intracranial aneurysm clips (except Sugita) with an appropriate operative conformation, history of intraorbital metal fragments, pacemakers and non-MRI compatible heart valves, inner ear implants, or history of claustrophobia in MRI
• Planned carotid surgery or endovascular intervention earlier than 10 weeks within the study period
• Serum triglycerides >400 mg/dl at screening
• Untreated or uncontrolled hypothyroidism or thyrotoxicosis
• Poorly controlled diabetes mellitus glycated hemoglobin ≥8.5%
• Poorly controlled hypertension
• History of malignancy within the past 2 years
• Evidence of recent severe infection (within 4 weeks)
• Current life-threatening condition other than vascular disease (e.g., very severe chronic airways disease, human immunodeficiency virus positive, life-threatening arrhythmias) that may prevent subject from completing the study
• History of myocardial infarction or cerebrovascular accident within the previous 2 weeks of screening
• Concomitant use of potent CYP450 3A4 inhibitors (e.g., clarithromycin, grapefruit juice [240 ml daily], itraconazole, ketoconazole)
• Chronic use of nonsteroidal anti-inflammatory drugs and oral steroid therapy
• Use of immunosuppressants (cyclosporine, methotrexate)
• Use of an investigational drug within 30 days or five half-lives (whichever is the longer) preceding the first dose of study medication
• Prior ipsilateral carotid endarterectomy or neck irradiation
• Alcohol or drug abuse within the past 6 months

Primary Endpoints:

• Change from baseline in signal intensity on USPIO-enhanced MRI in carotid plaque at 6 and 12 weeks

Secondary Endpoints:

• Total embolic count on transcranial Doppler

Drug/Procedures Used:

Patients with carotid stenosis >40% on duplex ultrasonography and who demonstrated intraplaque accumulation of USPIO on MRI at baseline were randomized in a double-blind manner to either 10 mg or 80 mg atorvastatin daily for 12 weeks. Follow-up imaging was obtained at 6 and 12 weeks.

Concomitant Medications:

Antiplatelet agent (95%)