Mercuri 1996.

Study characteristics
Methods	Study design: multicentre, parallel group, randomised, placebo‐controlled, double‐blind clinical trial Total duration of study: 3 years Details of any 'run‐in' period: "6 weeks single‐blind run‐in period in which they were treated with placebo and advised to follow a low‐fat diet meeting the recommendations of the European Atherosclerosis Society." Number of study centres and location: seven Lipid Clinics of Academic Medical Centres (Universities of Milan, Padua, Trieste, Bologna, Perugia, Rome and Naples), Italy Study setting and date of study: outpatients; March 1991 to June 1995
Participants	Number randomised: 305 participants Number lost to follow‐up/withdrawn: "12 of 42 dropouts suffered a serious adverse event: 5 of 12 events (4 MIs and 1 angina requiring coronary revascularisation) were of cardiovascular origin with 3 occurring in the pravastatin‐treated group. Cancer was detected in 7 participants (3 in the pravastatin group and 4 in the placebo group)." Number analysed: 305 participants Number of interest: 305 participants Mean age: 55 years old Age range: 45 to 65 years Gender: 162 men and 143 women Severity of condition: hypercholesterolaemia Diagnostic criteria: "LDL cholesterol levels between 3.88 and 6.47 mmol/L and triglycerides level < 2.82 mmol/L." Smoking history: 73 smokers Inclusion criteria: "male and female outpatients from the seven participating centres, without symptoms, signs or clinical history of CHD were screened (people with controlled hypertension, taking ACE‐inhibitors were eligible). Eligibility required ultrasonographic evidence of at least one uncomplicated carotid atherosclerotic lesion (clinically asymptomatic) in which the IMT ranges between 1.3 and 3.5 mm. The selected participants had, on at least 3 baseline determinations, a low‐density lipoprotein (LDL) cholesterol level, calculated according to Friedewald formula, between 150 and 250 mg/dL." Exclusion criteria: "plasma triglycerides > 250 mg/dL; uncontrolled hypertension with diastolic BP > 95 mmHg; history of myocardial infarction, angina pectoris on chronic treatment, stroke, TIA, or intermittent claudication; regular use of lipid‐lowering agents, anticoagulants or calcium channel blockers; persistent liver function abnormalities; history of allergies or intolerance to HMG CoA reductase inhibitors; other serious medical conditions (cancer, Type I or II diabetes), endocrine disorders, excessive ethanol consumption (> 50 g/day); chronic smoking (> 10 cigarettes/day)."
Interventions	Intervention: 40 mg pravastatin Comparison: placebo Concomitant medications: no details given Excluded medications: no details given
Outcomes	Primary outcome: "progression of early uncomplicated carotid lesions." Secondary outcome: "assessment of the drug safety, the evaluation of the effects of treatments on blood lipids, and to monitor morbid and fatal events." Time points reported: "all participants were seen every 3 months at their respective referral clinical centres."
Notes	Funding for trial: "Bristol‐Myers Squibb S.p.A. Italy, and in part by a grant from the Italian National Research Council." Notable conflicts of interest of trial authors: no details given Protocol: no details given
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Independent co‐ordinating centre controlled allocation."
Allocation concealment (selection bias)	Low risk	Quote: "Independent co‐ordinating centre controlled allocation."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote: "patients were double blindly randomized to either pravastatin (40 mg once daily) or its placebo manufactured to exactly resemble the pravastatin tablets." and "Double‐blind: participants and personnel."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote: "The video‐recorded examinations were interpreted centrally by readers masked to patient information using image processing workstations (PC with 286 microprocessors, image processing)."
Incomplete outcome data (attrition bias) All outcomes	Low risk	All prespecified outcomes reported Quote: "ITT used, 13% dropped out"
Selective reporting (reporting bias)	Low risk	All outcome measures have been reported in the results section
Other bias	Low risk	No other source of bias detected