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 years
Total cholesterol  3.5 mmol/l ( 135mg/dl)
Statin or vitamins not considered clearly indicated or contraindicated by patient’s own doctors
Notes: Eligibility for the study was guided chiefly by the "uncertainty principle". Patients were informed at the start of the study that lowering cholesterol was already known to reduce the risk of heart attacks, but that most people among the range of volunteers recruited were not then receiving any kind of cholesterol-lowering treatment. Prior to randomisation, the patient's own doctor was provided with the patient's lipid profile and a summary of existing evidence about cholesterol-lowering therapy, and asked to indicate if -- in their view -- a statin was likely to be needed by the patient (in which case the patient would not be randomised). Subsequently, randomised participants and their doctors were encouraged to start a non-study statin if it was considered to have become indicated (e.g. because of emerging evidence from other trials or changes in the patient's medical condition).

3. PRIOR DISEASE at BASELINE
Notes: Patients included with a history of coronary heart disease were predominantly older individuals, women and those with average or below average cholesterol levels at entry to the study. Those with cerebrovascular disease had a history of a stroke, transient ischaemic attack or carotid artery surgery. Those with peripheral vascular disease had intermittent claudication or a history of aortic or peripheral revascularisation. Patients with diabetes had either type 1 or type 2 diabetes.

4. AGE & SEX at BASELINE
Notes: Men and women aged between about 40 and 80 years were eligible for the study.

5. TOTAL & LDL CHOLESTEROL at BASELINE
Notes: Numbers are based on non-fasting lipid measurements taken at the initial visit prior to any lipid lowering therapy being taken. LDL cholesterol values were directly measured not calculated.

6. FACTORIAL TREATMENT COMPARISONS
Notes: Participants were randomly allocated to receive simvastatin or matching placebo tablets, with the average duration of treatment being 5 years. In addition, using a "2x2 factorial design", half of the patients in each of these groups were randomly allocated to receive vitamins and half were allocated placebo capsules. Assessment of cholesterol-lowering therapy involves comparing the 10,000 allocated active statin versus the 10,000 allocated placebo statin. Likewise, the assessment of antioxidant vitamin supplementation involves comparisons of the 10,000 allocated active vitamins versus the 10,000 allocated placebo vitamins.

7. VITAMINS: Average blood VITAMIN levels during follow-up
Notes: Effects on blood vitamin levels were assessed on non-fasting samples collected from about 5% of participants at baseline and at an average of 3 years of follow-up. Comparisons are based on all those allocated the study vitamins versus all those allocated placebo irrespective of whether or not they were still compliant (with any missing data imputed from the screening values, assuming non-compliance).

8. VITAMINS: CAUSE-SPECIFIC MORTALITY
Cause of
VITAMINS
PLACEBO
Rate ratio & 95% CI
death
(10269)
(10267)
VITAMINS better
PLACEBO better
Vascular
Coronary
664
630
Other vascular
214
210
ANY VASCULAR
878
840
5% SE 5
(8.6%)
(8.2%)
increase
(NS)
Non-vascular
Neoplastic
359
345
Respiratory
103
101
Other medical 90 82
Non-medical 16 21
NON-VASCULAR
568
549
4% SE 6
Notes: No significant differences were observed between treatment groups either overall or in any prespecified category of vascular or non-vascular mortality.
(5.5%)
(5.3%)
increase
(NS)
ALL CAUSES
1446
1389
4% SE 4
(14.1%)
(13.5%)
increase
(NS)
0.4
0.6
0.8
1.0
1.2
1.4

9. VITAMINS: SITE-SPECIFIC CANCER INCIDENCE
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
VITAMINS better
PLACEBO better
Gastrointestinal
228
223
Respiratory
181
165
Connective tissue 60 68
Genitourinary
247
284
Central nervous system 11 8
Haematological 58 58
Other 3 5
Not specified 42 43
ANY CANCER (except
800
817
2% SE 5
Notes: none
non melanoma skin)
(7.8%)
(8.0%)
reduction
(NS)
Non-melanoma skin
217
228
0.4
0.6
0.8
1.0
1.2
1.4

10. VITAMINS: STROKE INCIDENCE
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
VITAMINS better
PLACEBO better
Type
Ischaemic
345
354
Haemorrhagic 51 53
Unknown
122
115
Severity
Fatal
108
107
Severe 50 43
Moderate
127
135
Mild
158
169
Unknown 68 64
ALL STROKES
Notes: none
511
518
1% SE 6
(5.0%)
(5.0%)
reduction
(NS)
0.4
0.6
0.8
1.0
1.2
1.4

11. VITAMINS: CORONARY EVENTS & REVASCULARISATION
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
VITAMINS better
PLACEBO better
Major coronary event
Non-fatal MI
464
467
Coronary death
664
630
CORONARY EVENTS
1063
1047
2% SE 4
(10.4%)
(10.2%)
increase
(NS)
Revascularisation
Coronary
623
615
Non-coronary
472
510
REVASCULARISATIONS
Notes: none
1058
1086
3% SE 4
(10.3%)
(10.6%)
reduction
(NS)
0.4
0.6
0.8
1.0
1.2
1.4

12. VITAMINS: MAJOR VASCULAR EVENTS
PLACEBO
Rate ratio & 95% CI
event
(10269)
(10267)
VITAMINS better
PLACEBO better
Major coronary
1063
1047
Any stroke
511
518
Revascularisation
1058
1086
ANY OF ABOVE
2306
2312
0% SE 3
(22.5%)
(22.5%)
reduction
(NS)
Notes: No difference is seen between treatment groups in coronary events, strokes or the need for revascularisation. The large number of major vascular events on which this is based allows reliable assessment of the effects of study vitamins on this outcome in different circumstances.
0.4
0.6
0.8
1.0
1.2
1.4

13. VITAMINS: MAJOR VASCULAR EVENT
by PRIOR DISEASE
VITAMINS
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
VITAMINS better
PLACEBO better
Previous MI
1155
1094
Other CHD (not MI)
501
550
No prior CHD
CVD
190
194
PVD
376
371
Diabetes
311
332
Notes: No significant differences were observed between the treatment groups in the numbers of participants suffering a first major vascular event in these prior disease categories.
ALL PATIENTS
2306
2312
0% SE 3
(22.5%)
(22.5%)
reduction
(NS)
0.4
0.6
0.8
1.0
1.2
1.4

14. VITAMINS: MAJOR VASCULAR EVENT by YEAR
Year of
VITAMINS
PLACEBO
Rate ratio & 95% CI
follow-up
(10269)
(10267)
VITAMINS better
PLACEBO better 1
494
(4.8%)
514
(5.0%) 2
466
(4.8%)
449
(4.6%) 3
456
(5.0%)
412
(4.5%) 4
379
(4.4%)
388
(4.5%) 5+
511
(6.3%)
549
(6.7%)
ALL FOLLOW-UP
2306
(22.5%)
2312
(22.5%)
0% SE 3
reduction
Notes: No significant differences were observed between the treatment groups in the numbers of participants suffering a first major vascular event in the first 2 years or after more prolonged follow-up.
(NS)
0.4
0.6
0.8
1.0
1.2
1.4

15. VITAMINS: MAJOR VASCULAR EVENT by YEAR1 2 3 4 5 6 10 15 20 25 30
Years of follow-up
VITAMINS
PLACEBO
4(8)
-3(5)
People suffering events (%)
-4(5)
0(4)
2(3)
Notes: This life-table plot provides no evidence of effects beginning to emerge with more prolonged follow-up.
Benefit/1000 (SE):
2(18)
VITAMINS

16. VITAMINS: CATARACT and FRACTURES
Notes: There was no significant support for the suggestion from observational studies that anti-oxidant vitamins might prevent cataracts or fractures.

17. VITAMINS: COGNITIVE IMPAIRMENT (TICS-m <22/39) at Final Follow-up
Notes: The modified Telephone Interview for Cognitive Status (TICS-m) was used to assess cognitive function, with a score of 22/39 pre-specified as indicating some cognitive impairment. Despite apparent discrimatory power, as illustrated by higher proportions of older individuals scoring below 22, there is no evidence of an effect of vitamins on this measure.

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
Notes: none

19. FACTORIAL TREATMENT COMPARISONS
Notes: Participants were randomly allocated to receive simvastatin or matching placebo tablets, with the average duration of treatment being 5 years. In addition, using a "2x2 factorial design", half of the patients in each of these groups were randomly allocated to receive vitamins and half were allocated placebo capsules. Assessment of cholesterol-lowering therapy involves comparing the 10,000 allocated active statin versus the 10,000 allocated placebo statin. Likewise, the assessment of antioxidant vitamin supplementation involves comparisons of the 10,000 allocated active vitamins versus the 10,000 allocated placebo vitamins.

20. STATIN USE: Compliance with study simvastatin or use of non-study statin
Notes: During the study, each participant's own doctors were free to monitor cholesterol levels and were encouraged to start a non-study statin if they considered it had become indicated. The study simvastatin or placebo could be continued if the non-study statin dose was no greater than simvastatin 40mg daily (or equivalent in lipid-lowering potency of another statin). On average during the study, about one-sixth of participants allocated placebo were prescribed a non-study statin and about one-sixth of those allocated study simvastatin stopped taking statin. So, instead of all of those allocated simvastatin taking it throughout the study and none of those allocated placebo taking a statin, the actual difference between these groups in statin use was only about two-thirds of full compliance. (At the final follow-up 4002 participants were taking a non-study statin, with 53% using simvastatin, 28% atorvastatin, 10% pravastatin, 5% cerivastatin and 4% fluvastatin.)

21. Difference in LDL CHOLESTEROL (SIMVASTATIN - PLACEBO)
0.5 20
mmol/l
Years of follow-up
mg/dl
(±SE)
(±SE) 1 2 3 4 5
0.0
-0.5
-20
-1.0
-40
-1.5
-60
Average: ± 0.02 mmol/l
-2.0
Notes: These LDL cholesterol differences are based on intention to treat comparisons, with missing data imputed from initial pre-treatment screening values. Simvastatin 40mg daily produces a reduction in LDL cholesterol of about 1.5 mmol/l in this population. But, with 2/3 average compliance during the study, the average LDL difference was 1.0 mmol/l.
- 37 ± 0.8 mg/dl
-80

22. HPS assesses 2/3 of the effect of actually using 40mg simvastatin daily
Average proportions using statin during HPS: /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
Notes: none

23. SIMVASTATIN 40mg daily: Muscle symptoms
Notes: Participants were asked about unexplained muscle pain or weakness at each follow-up. On average about 5% of participants reported such symptoms at each visit, but at no time during the study was there any significant difference between those allocated simvastatin or placebo. If participants stopped study medication the reasons for doing so were recorded.

24. SIMVASTATIN 40mg daily: Safety monitoring
Notes: Numbers are of participants ever having values in the ranges shown. Participants were seen regularly at 4 month intervals during the first year and then six monthly during the study. A blood sample was taken at each visit and the liver enzyme alanine transaminase (ALT) routinely measured. In addition, if unexplained muscle pain or weakness was reported (or participants were taking non-study statin treatment as well as study simvastatin or placebo tablets) then creatine kinase (CK) was measured . In addition some CK values were reported by the managing doctor.

25. SIMVASTATIN: CAUSE-SPECIFIC MORTALITY
Cause of
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
death
(10269)
(10267)
STATIN better
PLACEBO better
Vascular
Coronary
587
707
Other vascular
194
230
ANY VASCULAR
781
937
17% SE 4
(7.6%)
(9.1%)
reduction
(2P<0.0001)
Non-vascular
Neoplastic
359
345
Respiratory 90
114
Other medical 82 90
Non-medical 16 21
NON-VASCULAR
547
570
5% SE 6
Notes: There was a significant reduction in total mortality which is chiefly driven by a more definite reduction in vascular mortality with no evidence of any excess of non-vascular mortality.
(5.3%)
(5.6%)
reduction
(NS)
ALL CAUSES
1328
1507
13% SE 4
(12.9%)
(14.7%)
reduction
(2P<0.001)
0.4
0.6
0.8
1.0
1.2
1.4

26. SIMVASTATIN: SITE-SPECIFIC CANCER INCIDENCE
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better
PLACEBO better
Gastrointestinal
228
223
Respiratory
179
167
Connective tissue 60 68
Genitourinary
259
272
Central nervous system 12 7
Haematological 64 52
Other 6 2
Not specified 36 49
ANY CANCER (except
814
803
0% SE 5
Notes: There were no significant differences between the treatment groups in cancer incidence during the study.
non melanoma skin)
(7.9%)
(7.8%)
increase
(NS)
Non-melanoma skin
243
202
0.4
0.6
0.8
1.0
1.2
1.4

27. SIMVASTATIN: STROKE INCIDENCE
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better
PLACEBO better
Type
Ischaemic
290
409
Haemorrhagic 51 53
Unknown
103
134
Severity
Fatal 96
119
Severe 42 51
Moderate
107
155
Mild
138
189
Unknown 61 71
ALL STROKES
Notes: There was a clear and definite effect of simvastatin on the incidence of first stroke, with the benefits due chiefly to effects on ischaemic stroke (but with no adverse effect on haemorrhagic stroke).
For stroke severity the numbers relate to the most severe stroke that could be classified (so these categories are mutually exclusive).
444
585
25% SE 5
(4.3%)
(5.7%)
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

28. SIMVASTATIN: CORONARY EVENTS & REVASCULARISATION
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better
PLACEBO better
Major coronary event
Non-fatal MI
357
574
Coronary death
587
707
CORONARY EVENTS
898
1212
27% SE 4
(8.7%)
(11.8%)
reduction
(2P< )
Revascularisation
Coronary
513
725
Non-coronary
450
532
REVASCULARISATIONS
Notes: none
939
1205
24% SE 4
(9.1%)
(11.7%)
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

29. SIMVASTATIN: MAJOR VASCULAR EVENTS
PLACEBO
Rate ratio & 95% CI
event
(10269)
(10267)
STATIN better
PLACEBO better
Major coronary
898
1212
Any stroke
444
585
Revascularisation
939
1205
ANY OF ABOVE
2033
2585
24% SE 3
(19.8%)
(25.2%)
reduction
(2P< )
Notes: Similar proportional reductions in major coronary events, in strokes and in revascularisations yield a very definite effect on the first occurrence of any of these “major vascular events“. The extreme statistical significance of this reduction and the very large number of events and on which it is based, allows reliable assessment of the effects of treatment in various different circumstances.
0.4
0.6
0.8
1.0
1.2
1.4

30. SIMVASTATIN: MAJOR VASCULAR EVENT by YEAR
Year of
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
follow-up
(10269)
(10267)
STATIN better
PLACEBO better 1
481
(4.7%)
527
(5.1%) 2
377
(3.9%)
538
(5.6%) 3
359
(3.9%)
509
(5.6%) 4
331
(3.8%)
436
(5.2%) 5+
485
(5.8%)
575
(7.3%)
ALL FOLLOW-UP
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
Notes: During the first year the reduction in major vascular events was not significant, but subsequently it was highly significant during each separate year (even though, by the end of year 3, about one-sixth of simvastatin-allocated participants had stopped their study treatment and about one-sixth of those allocated placebo had started statin therapy).
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

31. SIMVASTATIN: MAJOR VASCULAR EVENT by YEAR1 2 3 4 5 6 10 15 20 25 30
Years of follow-up
SIMVASTATIN
PLACEBO
54(7)
46(5)
People suffering events (%)
35(5)
20(4)
5(3)
Notes: After the first year, there were highly significant reductions of about one quarter in the event rates during each separate year. This leads to continued divergence of the lines in this life-table plot of the effect of simvastatin on the incidence of a first major vascular event, which implies that benefits would increase with longer duration treatment and follow-up.
Benefit/1000 (SE):
60(18)
SIMVASTATIN

32. SIMVASTATIN: MAJOR VASCULAR EVENT
by PRIOR DISEASE
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better
PLACEBO better
Previous MI
999
(23.5%)
1250
(29.4%)
Other CHD (not MI)
460
(18.9%)
591
(24.2%)
No prior CHD
CVD
172
(18.7%)
212
(23.6%)
PVD
327
(24.7%)
420
(30.5%)
Diabetes
276
(13.8%)
367
(18.6%)
Notes: There were similar proportional reductions in the numbers of participants suffering a first major vascular event in these prior disease categories
ALL PATIENTS
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

33. SIMVASTATIN: MAJOR VASCULAR EVENT by AGE & SEX
Baseline
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
feature
(10269)
(10267)
STATIN better
PLACEBO better
Age
< 65
831
(16.9%)
1091
(22.1%)
512
(20.9%)
665
(27.2%)
548
(23.8%)
620
(27.7%) 75
142
(23.1%)
209
(32.3%)
Sex
Male
1666
(21.6%)
2135
(27.6%)
Female
367
(14.4%)
450
(17.7%)
Notes: There were similar proportional reductions in risk of major vascular events at different ages, and in women as well as men.
ALL PATIENTS
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

34. SIMVASTATIN: COGNITIVE IMPAIRMENT (TICS-m <22/39) at Final Follow-up
Notes: The modified Telephone Interview for Cognitive Status (TICS-m) was used to assess cognitive function, with a score of 22/39 pre-specified as indicating some cognitive impairment. Despite apparent discrimatory power, as illustrated by higher proportions of older individuals scoring below 22, there is no evidence of an effect of simvastatin on this measure.

35. SIMVASTATIN: MAJOR VASCULAR EVENT by SMOKING & TREATED HYPERTENSION
Baseline
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
feature
(10269)
(10267)
STATIN better
PLACEBO better
Smoking
Never regular
406
(15.7%)
531
(20.6%)
Ex-cigarette
1298
(20.8%)
1638
(26.3%)
Current
329
(22.8%)
416
(28.4%)
Treated hypertension
Yes
942
(22.4%)
1195
(28.1%) No
1091
(18.0%)
1390
(23.1%)
Notes: Similar proportional reductions in risk of major vascular events are seen when participants are subdivided by smoking status or history of treated hypertension.
ALL PATIENTS
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

36. SIMVASTATIN: MAJOR VASCULAR EVENT by HDL CHOLESTEROL & TRIGLYCERIDES
Lipid levels
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
at entry
(10269)
(10267)
STATIN better
PLACEBO better
HDL cholesterol (mmol/l)
< 0.9 (35 mg/dl)
818
(22.6%)
1064
(29.9%)
0.9 < 1.1
560
(20.0%)
720
(25.1%)
1.1 (43 mg/dl)
655
(17.0%)
801
(20.9%)
Triglycerides (mmol/l)
< 2.0 (177 mg/dl)
1101
(18.3%)
1432
(23.7%)
2.0 < 4.0
743
(21.6%)
939
(27.3%)
4.0 (354 mg/dl)
189
(23.2%)
214
(27.1%)
Notes: Similar proportional reductions in risk of major vascular events are seen when participants are subdivided by baseline HDL cholesterol or triglycerides levels.
ALL PATIENTS
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

37. SIMVASTATIN: Average LDL DIFFERENCE (mmol/l ± se) by BASELINE LDL cholesterol
Notes: none

38. SIMVASTATIN: Average LDL DIFFERENCE (mg/dl ± se) by BASELINE LDL cholesterol
Notes: none

39. SIMVASTATIN: MAJOR VASCULAR EVENT by LDL & TOTAL CHOLESTEROL
Lipid levels
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
at entry
(10269)
(10267)
STATIN better
PLACEBO better
LDL cholesterol (mmol/l)
< 3.0 (116 mg/dl)
598
(17.6%)
756
(22.2%)
3.0 < 3.5
484
(19.0%)
646
(25.7%)
3.5 (135 mg/dl)
951
(22.0%)
1183
(27.2%)
Total cholesterol (mmol/l)
< 5.0 (193 mg/dl)
360
(17.7%)
472
(23.1%)
5.0 < 6.0
744
(18.9%)
964
(24.5%)
> 6.0 (323 mg/dl)
929
(21.6%)
1149
(26.8%)
Notes: Similar proportional reductions in risk of major vascular events are seen when participants are subdivided by baseline LDL or total cholesterol levels.
ALL PATIENTS
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

40. SIMVASTATIN: MAJOR VASCULAR EVENT in upper & lower thirds of baseline LDL30
Statin-allocated
Placebo-allocated 25
Upper
LDL third
% with major vascular events 20
Lower
LDL third 15
Notes: This apparent continuous association between LDL cholesterol and risk of major vascular event is consistent with the original hypothesis of the study that similar risk reductions would be seen irrrespective of baseline LDL cholesterol. It is also consistent with larger reductions in cholesterol being associated with greater proportional benefits (which is being tested by direct randomised comparisons in on-going studies).
1.5
2.0
2.5
3.0
3.5
4.0
Average LDL cholesterol (mmol/l)

41. SIMVASTATIN: MAJOR VASCULAR EVENT by LDL CHOLESTEROL
Lipid levels
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
at entry
(10269)
(10267)
STATIN better
PLACEBO better
LDL cholesterol (mg/dl)
< 100
282
(16.4%)
358
(21.0%)
100 < 130
668
(18.9%)
871
(24.7%)
130
1083
(21.6%)
1356
(26.9%)
ALL PATIENTS
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
Notes: Even among the 3421 patients with entry LDL cholesterol levels below 100mg/dl (about 2.6 mmol/l), a similar proportional reduction in risk of major major events is seen to that among participants presenting with higher LDL levels.
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

42. SIMVASTATIN: MAJOR VASCULAR EVENT by CREATININE & VITAMINS
Baseline
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
feature
(10269)
(10267)
STATIN better
PLACEBO better
Creatinine
Normal
1851
(19.2%)
2317
(24.2%)
Elevated
182
(28.2%)
268
(39.2%)
Vitamin allocation
Vitamins
1014
(19.7%)
1292
(25.2%)
Placebo
1019
(19.8%)
1293
(25.2%)
ALL PATIENTS
Notes: Patients with known chronic renal failure or creatinine >200 µmol/l were excluded from the study. Participants in the study classified as having elevated creatinine were men with creatinine >130 µmol/l and women >110 µmol/l.
There was no evidence of any effect of vitamin allocation on the size of the benefit seen with simvastatin.
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

43. SIMVASTATIN: MAJOR VASCULAR EVENT
by OTHER TREATMENT
Baseline
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
treatment
(10269)
(10267)
STATIN better
PLACEBO better
Aspirin
Yes
1370
(21.1%)
1784
(27.4%) No
663
(17.5%)
801
(21.3%)
ACE inhibitor
Yes
495
(24.9%)
568
(28.5%) No
1538
(18.6%)
2017
(24.4%)
Beta-blocker
Yes
519
(19.5%)
705
(26.9%) No
1514
(19.9%)
1880
(24.6%)
Calcium antagonist
Yes
788
(24.7%)
1023
(31.2%)
Notes: Similar proportional reductions in risk of major vascular events are seen among those taking or not taking other commonly prescribed cardioprotective medications. No
1245
(17.6%)
1562
(22.4%)
ALL PATIENTS
2033
(19.8%)
2585
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

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)
Notes: none

45. Millions of people with relevant conditions
Notes: It has been estimated that about 25 million people worldwide are currently being treated with a statin. World Health Organisation statistics indicate that there are about 200 million people worldwide with CHD, stroke, other occlusive vascular disease or diabetes. Consequently, the present findings are directly relevant to starting statin treatment in some tens of millions of people at increased risk of heart attacks and strokes.