Ballantyne 2004.

Methods	Design: multinational, randomised, placebo‐controlled, extension study Number of study centres: multinational (conducted in 16 countries, but did not report the number of study centres) Setting: outpatient Patient recruitment: not reported Duration of study: 12 months Clinical setting: primary hypercholesterolaemia
Participants	Enrolment (N): 246 Randomised (N): intervention: 201; control:45 Withdrawn (N): not reported Lost to follow‐up (N): not reported Completed the study (N): intervention: 167; control: 39 Analysed (N): intervention: 201; control:45 Age (years) (mean, range): intervention: 57.6 (26–86); control: 58.5 (34–76) Sex (male, N, %): intervention: 78 (39%); control: 23 (51 %) Smoking history (N, %): intervention: 26 (13% ); control: 4 (9% ) BMI (kg/m²): not reported Diabetes (N, %): intervention: 14 (7%) ; control: 1 (2%) Hypertension (N, %): intervention: 68 (34%); control: 19 (42%) History of CHD (N, %): intervention:23(11%) ; control:6(13%) Statin pretreatment (N, %): not reported Inclusion criteria: this was an extension study of a 12‐week RCT comparing ezetimibe 10 mg; atorvastatin 10 mg, 20 mg, 40 mg or 80 mg; ezetimibe + atorvastatin 10 mg, 20 mg, 40 mg or 80 mg or placebo. Patients who successfully completed the base study were offered enrolment in the 12‐month extension study. The inclusion criteria of the parent study: men and women >=18 years of age were screened for primary hypercholesterolaemia, defined as calculated LDL‐C 7 of 145 to 250 mg/dL, inclusive, and triglyceride levels <=350 mg/dL. Exclusion criteria: the exclusion criteria of the parent study included congestive heart failure (defined as New York Heart Association class III or IV heart failure 8); uncontrolled cardiac arrhythmias; MI, coronary bypass surgery, or angioplasty within 6 months of study entry; history of unstable or severe peripheral artery disease within 3 months of study entry; unstable angina pectoris; uncontrolled or newly diagnosed (within 1 month of study entry) diabetes mellitus; unstable endocrine or metabolic diseases known to influence serum lipids and lipoproteins; known impairment of renal function; active or chronic hepatic or hepatobiliary disease; and known coagulopathy.
Interventions	Intervention: ezetimibe + atorvastatin 10 mg Comparison: placebo + atorvastatin 10 mg Quote: "Following intervals of 6 weeks, patients who were not at their National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP II) LDL‐C goals were titrated to the next higher dose of atorvastatin, up to a maximum dose of atorvastatin (80 mg)." Details of any 'run‐in' period: not reported Concomitant medications: not reported Excluded medications: not reported
Outcomes	Primary: treatment‐emergent adverse events; percent change from baseline to endpoint in LDL‐C, total cholesterol (TC), HDL‐C and triglyceride and proportion of patients attaining the NCEP ATP II LDL‐C goal
Notes	Funding: Study was funded by Schering‐Plough Research Institute and Merck/Schering‐Plough Pharmaceuticals. Emailed trialists to ask for details number of discontinuations due to patient request, non‐compliance with protocol and lost to follow‐up. No response.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The author reported that they randomly assigned patients but the details were not available.
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind, using matching placebo.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	A central laboratory performed all clinical laboratory analyses (lipids, liver enzymes, creatine kinases, etc.).
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Discontinuations due to patient request, non‐compliance with protocol and lost to follow‐up were not different between treatment groups". The efficacy and safety analyses were performed in the intention‐to‐treat population.
Selective reporting (reporting bias)	Unclear risk	No protocol published, or trials registry record found.
Other bias	Unclear risk	Insufficient information to permit judgement. Study was funded by Schering‐Plough Research Institute and Merck/Schering‐Plough Pharmaceuticals.