Underhill 2008.

Study characteristics
Methods	Study design: randomised, double‐blind, multicentre trial Total duration of study: 2 years Details of any 'run‐in' period: "all cholesterol‐lowering drugs were discontinued during a 6‐week dietary lead‐in period, after which baseline serum lipid values were obtained." Number of study centres and location: 2 centres, University of Washington, Seattle, WA, and the University of Utah, Salt Lake City, Utah Study setting and date of study: outpatients; 6 January 2000 (first participant enrolled), to 15 August 2004 (last participant completed)
Participants	Number randomised: 43 participants Number lost to follow‐up/withdrawn: "4 of 43 patients did not complete the study because of an adverse event (n = 2), withdrawn consent (n = 1), or other reasons (n = 1). Of the 39 participants who completed the study, all remained asymptomatic and 33 (n low = 13, n high = 20) had matched baseline and 2‐year scans of sufficient image quality for identification of the vessel boundaries and automated compositional analysis." Number analysed: 33 participants Number of interest: 33 participants Mean age: 65.2 years Age range: 18 years and older Gender: 21 men and 12 women Severity of condition: neurologically asymptomatic patients Diagnostic criteria: "fasting low‐density lipoprotein cholesterol ≥ 100 and b250 mg/dL and 16% to 79% carotid stenosis by duplex ultrasound." Smoking history: 7 current smokers Inclusion criteria "Fasting blood low‐density lipoprotein cholesterol level as defined by the protocol Diagnosed carotid arterial stenosis" Exclusion criteria "The use of lipid‐lowering drugs or dietary supplements after Visit 1 Heavy or total occlusion of the carotid artery or recent stroke Uncontrolled hypertension, hypothyroidism, alcohol or drug abuse"
Interventions	Intervention: rosuvastatin low dose (5 mg) Comparison: rosuvastatin high dose (40/80 mg/d) Concomitant medications: no details given Excluded medications: no details given
Outcomes	Primary outcome: changes in carotid wall volume as measured by MRI scan Secondary outcomes: "safety: adverse events & abnormal laboratory markers; other changes in the structure and composition of the carotid arterial wall as defined in the protocol." Time points reported "Changes in carotid wall: time frame: at 40 weeks and 104 weeks Safety: time frame: 2 weekly for first 4 weeks then 4 weekly Other changes: time frame: at 40 weeks and 104 weeks"
Notes	Funding for trial: "this research was supported by AstraZeneca, London, UK, and the National Institutes of Health, Bethesda, MD (T‐32, HL07838)" Notable conflicts of interest of trial authors: no details given Protocol: NCT00654394
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Study participants were randomized to receive rosuvastatin low dose (5 mg) or high dose (40/80 mg/d) for 2 years."
Allocation concealment (selection bias)	Unclear risk	Not reported
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "The randomized, double‐blind ORION trial."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "33 patients had matched serial MRI scans to compare by reviewers blinded to clinical data, dosage, and temporal sequence of scans."
Incomplete outcome data (attrition bias) All outcomes	Low risk	All outcome measures have been reported in the results section
Selective reporting (reporting bias)	Low risk	All prespecified outcomes reported
Other bias	Low risk	No other source of bias detected