2. ELIGIBILITY: MRC/BHF Heart Protection Study Increased risk of CHD death due to prior disease: Myocardial infarction or other coronary heart disease; Occlusive disease of non-coronary arteries; or Diabetes mellitus or treated hypertension Age 40-80 years Total cholesterol >3.5 mmol/l (>135mg/dl) Statin or vitamins not considered clearly indicated or contraindicated by patient’s own doctors

3. PRIOR DISEASE at BASELINE

4. AGE & SEX at BASELINE

5. TOTAL & LDL CHOLESTEROL at BASELINE

6. FACTORIAL TREATMENT COMPARISONS

7. VITAMINS: Average blood VITAMIN levels during follow-up

16. VITAMINS: CATARACT and FRACTURES

17. VITAMINS: COGNITIVE IMPAIRMENT (TICS-m <22/39) at Final Follow-up

18. VITAMINS: Summary of findings This antioxidant vitamin regimen (600mg E, 250mg C & 20mg beta carotene daily) increased blood vitamin levels substantially These vitamins appeared to be safe, but did not reduce the 5-year risks of any type of vascular disease, cancer or other major outcome Given these results, continued recommendation of supplementation with such vitamins is difficult to justify

19. FACTORIAL TREATMENT COMPARISONS

20. STATIN USE: Compliance with study simvastatin or use of non-study statin

22. HPS assesses 2/3 of the effect of actually using 40mg simvastatin daily Average proportions using statin during HPS: 5/6 of active group vs 1/6 of control group LDL difference in HPS (active vs control group) is ~2/3 of LDL difference from actually using statin Risk reduction in HPS (active vs control group) is ~2/3 of risk reduction from actually using statin ACTUAL EFFECT = 1.5 x APPARENT EFFECT

23. SIMVASTATIN 40mg daily: Muscle symptoms

24. SIMVASTATIN 40mg daily: Safety monitoring

34. SIMVASTATIN: COGNITIVE IMPAIRMENT (TICS-m <22/39) at Final Follow-up

37. SIMVASTATIN: Average LDL DIFFERENCE (mmol/l ± se) by BASELINE LDL cholesterol

38. SIMVASTATIN: Average LDL DIFFERENCE (mg/dl ± se) by BASELINE LDL cholesterol

40. SIMVASTATIN: MAJOR VASCULAR EVENT in upper & lower thirds of baseline LDL Average LDL cholesterol (mmol/l) 15 20 25 30 1.52.02.53.03.54.0 Statin-allocated Placebo-allocated Upper LDL third Lower LDL third % with major vascular events

44. SIMVASTATIN: Main conclusions After allowance for non-compliance, 40mg daily simvastatin safely reduces the risk of heart attack, of stroke, and of revascularisation by about one-third 5 years of statin treatment typically prevents these “major vascular events” in about: 100 of every 1000 people with previous MI 80 " " " other CHD 70 " " " cerebrovascular disease 70 " " " other arterial disease 70 " " " diabetes (age 40+) irrespective of cholesterol level (or age, or sex, or other treatments)

45. Millions of people with relevant conditions