REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification

Inclusion Criteria:

• Patients must be aged at least 50 at the time of initial invitation, and at leastone of the following inclusion criteria must be satisfied:

• History of MI; or

• Cerebrovascular atherosclerotic disease (i.e. history of presumed ischaemicstroke or carotid revascularization); or

• Peripheral arterial disease (i.e. history of non-coronary revascularization,including aortic aneurysm repair or graft); or

• Diabetes mellitus with other evidence of symptomatic coronary heart disease (i.e. treatment or hospitalization for angina, or a history of coronaryrevascularization or acute coronary syndrome).

Exclusion Criteria:

• None of the following must be satisfied:

• Acute MI, acute coronary syndrome or stroke within 4 weeks prior to ScreeningVisit or during Run-in (but such individuals may be entered later, ifappropriate);

• Planned coronary revascularization procedure within the next 6 months (suchindividuals may be entered later, if appropriate);

• Definite history of chronic liver disease, or abnormal liver function (i.e.alanine transaminase (ALT) >2x the upper limit of normal (ULN)). Note:Individuals with a history of acute hepatitis are eligible provided this ALTlimit is not exceeded;

• Severe renal insufficiency (i.e. creatinine >200 µmol/L [2.3 mg/dL], dialysisor functioning renal transplant);

• Evidence of active inflammatory muscle disease (e.g. dermatomyositis,polymyositis), or creatine kinase (CK) >3x ULN;

• Previous significant adverse reaction to a statin or anacetrapib;

• Current treatment with any of the following lipid-lowering treatments: (i) a regimen considered to produce substantially greater LDL cholesterolreduction than atorvastatin 80 mg daily for individuals in non-Asian countriesor 20 mg daily for those in North East Asia; or (ii) fibric acid derivative ("fibrate", including gemfibrozil); or (iii) niacin (nicotinic acid) at dosesabove 100 mg daily

• Concurrent treatment with a medication that is contraindicated with anacetrapibor atorvastatin: (i) any potent CYP3A4 inhibitor, such as:

1. macrolide antibiotics (erythromycin, clarithromycin, telithromycin);
2. systemic imidazole or triazole antifungals (e.g. itraconazole,posaconazole);
3. protease inhibitors (e.g. atazanavir);
4. nefazodone (ii) ciclosporin (iii) daptomycin (iv) systemic use of fusidic acid Note: Individuals who are taking such drugs temporarily may be re-screenedwhen they discontinue them, if considered appropriate;

• Known to be poorly compliant with clinic visits or prescribed medication;

• Medical history that might limit the individual's ability to take trialtreatments for the duration of the study (e.g. severe respiratory disease;history of cancer or evidence of spread within last 5 years, other thannon-melanoma skin cancer; or recent history of alcohol or substance misuse);

• Women of child-bearing potential (unless using adequate contraception);

• Current participation in a clinical trial with an unlicensed drug or device.

Individuals will also be excluded at the Screening visit if it is considered unlikely that they will achieve total cholesterol <3.5 mmol/L (135 mg/dL) on the highest atorvastatin dose available in their region (atorvastatin 80 mg daily in non-Asian countries or 20 mg daily in North East Asia).

In addition, individuals will be excluded at the Randomization visit if any of the following are true:

• Total cholesterol above 4 mmol/L [155 mg/dL]

• Non-compliant with run-in treatment (<90% scheduled run-in medication taken)

• Individual is no longer willing to be randomized into the 4-5 year trial

• The individual's doctor is of the view that their patient should not be randomized.