1. Baseline characteristics of HPS participants by prior diabetes
Notes: none

2. HPS: Baseline lipids (mmol/L) and apolipoproteins (g/L) by prior diabetes
Notes: Average lipid levels (mmol/L) at baseline in those with and without diagnosed diabetes.

3. HPS: Baseline lipids (mg/dL) and apolipoproteins (g/L) by prior diabetes
Notes: Average lipid levels (mg/dL) at baseline in those with and without diagnosed diabetes.

4. HPS: 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.

5. HPS: Mean (SE) differences in lipids during follow-up by diabetes
Notes: Intention-to-treat comparisons (simvastatin minus placebo) of lipid levels during follow-up in those with and without diabetes. Missing data imputed from initial pretreatment screening values.

6. SIMVASTATIN: MAJOR CORONARY EVENTS and STROKE by prior DIABETES
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
Vascular event
& disease group
(10269)
(10267)
Major coronary events
Diabetes
279
377
(9.4%)
(12.6%)
No diabetes
619
835
(8.5%)
(11.5%)
All patients
898
1212
(8.7%)
(11.8%)
27% SE 4
reduction
(2P< )
Strokes
149
193
(5.0%)
(6.5%)
295
392
(4.0%)
(5.4%)
444
585
(4.3%)
(5.7%)
25% SE 5
0.4
0.6
0.8
1.0
1.2
1.4
Notes: Similar proportional reductions are seen both in those with and without diabetes in major coronary events (non-fatal myocardial infarction or coronary death) and in strokes (fatal or non-fatal stroke).

7. SIMVASTATIN: REVASCULARISATIONS and
MAJOR VASCULAR EVENTS by prior DIABETES
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
Vascular event
& disease group
(10269)
(10267)
Revascularisations
Diabetes
260
309
(8.7%)
(10.4%)
No diabetes
679
896
(9.3%)
(12.3%)
All patients
939
1205
(9.1%)
(11.7%)
24% SE 4
reduction
(2P< )
Major vascular events
601
748
(20.2%)
(25.1%)
1432
1837
(19.6%)
(25.2%)
ALL PATIENTS
2033
2585
(19.8%)
24% SE 3
0.4
0.6
0.8
1.0
1.2
1.4
Notes: Similar proportional reductions in major coronary events, strokes and revascularisation seen in those with and without diabetes yields a very clear effect on the first occurrence of any of these “major vascular events”. The extreme statistical significance of the reduction in the rate of first major vascular event (Z score =9.3), and the large number of events on which it is based, allows reliable assessment of the effects of treatment in various different circumstances.

8. SIMVASTATIN: MAJOR VASCULAR EVENT by YEAR
in DIABETIC PATIENTS
Year
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
of follow-up
(2978)
(2985)
STATIN better
PLACEBO better 1
143
(4.8%)
141
(4.7%) 2
110
(3.9%)
150
(5.3%) 3
109
(4.0%)
172
(6.5%) 4
101
(3.9%)
138
(5.6%) 5+
138
(5.7%)
147
(6.4%)
22% SE 5
ALL FOLLOW-UP
During the first year after randomisation in participants with diabetes there was little apparent effect of simvastatin allocation on the incidence of first major vascular event, but by year 2 there was a highly significant reduction with similar proportional benefits seen in each separate subsequent 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 placebo allocated participants had started statin therapy).
601
(20.2%)
748
(25.1%)
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

9. SIMVASTATIN: MAJOR VASCULAR EVENTS by YEAR
in DIABETIC PATIENTS
Years of follow-up
PLACEBO
SIMVASTATIN
Benefit/1000(SE)
-1(6)
13(8)
34(9)
47(10)
51(15)
58(48)
Logrank p< 1 2 3 4 5 6 10 15 20 25 30
People suffering events (%)
Notes: Life-table plot of the effects of simvastatin allocation on percentage of diabetic patients having a first major vascular event suggests that benefits increase with longer duration of treatment and follow-up.

10. SIMVASTATIN: MAJOR VASCULAR EVENTS by PRIOR DISEASE & prior DIABETES
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
Prior disease &
diabetes
(10269)
(10267)
CHD
Diabetes
325
381
(33.4%)
(37.8%)
No diabetes
1134
1460
(19.8%)
(25.7%)
Other CVD
141
171
(25.6%)
(32.9%)
287
362
(24.4%)
No CVD
135
196
(9.3%)
(13.5%)
ALL PATIENTS
2033
2585
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events in those with and without diabetes irrespective of prior vascular disease. CHD = any coronary heart disease at entry, CVD = any cardiovascular disease at entry.

11. SIMVASTATIN: MAJOR VASCULAR EVENTS
by SEX & prior DIABETES
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
Sex &
diabetes
(10269)
(10267)
Male
Diabetes
471
580
(22.8%)
(27.8%)
No diabetes
1195
1555
(21.1%)
(27.6%)
Female
130
168
(14.2%)
(18.6%)
237
282
(14.6%)
(17.2%)
ALL PATIENTS
2033
2585
(19.8%)
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events in men and women, both with and without diabetes.

12. SIMVASTATIN: MAJOR VASCULAR EVENTS
by AGE & prior DIABETES
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
Age &
diabetes
(10269)
(10267)
<65 y
Diabetes
263
341
(15.7%)
(20.1%)
No diabetes
568
750
(17.6%)
(23.1%) 
65 y
338
407
(25.9%)
(31.6%)
864
1087
(21.3%)
(26.9%)
ALL PATIENTS
2033
2585
(19.8%)
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events in those with and without diabetes at different ages.

13. SIMVASTATIN: MAJOR VASCULAR EVENTS by LDL CHOLESTEROL & prior DIABETES
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
LDL cholesterol &
diabetes
(10269)
(10267)
<3.0 mmol/L
Diabetes
191
252
(15.7%)
(20.9%)
No diabetes
407
504
(18.8%)
(22.9%) 
3.0 mmol/L
410
496
(23.3%)
(27.9%)
1025
1333
(20.0%)
(26.2%)
ALL PATIENTS
2033
2585
(19.8%)
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events irrespective of various lipid values at baseline, both in those with and those without diabetes.

14. SIMVASTATIN: MAJOR VASCULAR EVENTS by TRIGLYCERIDES & prior DIABETES
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
Triglycerides &
diabetes
(10269)
(10267)
<2.0 mmol/L
Diabetes
270
364
(16.8%)
(22.8%)
No diabetes
831
1068
(18.9%)
(24.1%) 
2.0 mmol/L
331
384
(27.6%)
601
769
(20.8%)
(27.1%)
ALL PATIENTS
2033
2585
(19.8%)
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events irrespective of various lipid values at baseline, both in those with and those without diabetes.

15. SIMVASTATIN: MAJOR VASCULAR EVENTS by HDL CHOLESTEROL & prior DIABETES
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
HDL cholesterol &
diabetes
(10269)
(10267)
<0.9 mmol/L
Diabetes
288
356
(25.9%)
(31.1%)
No diabetes
530
708
(21.1%)
(29.3%) 
0.9 mmol/L
313
392
(16.8%)
(21.3%)
902
1129
(18.9%)
(23.2%)
ALL PATIENTS
2033
2585
(19.8%)
(25.2%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events irrespective of various lipid values at baseline, both in those with and those without diabetes.

16. SIMVASTATIN: MAJOR VASCULAR EVENTS
by ApoB/ApoA1 ratio & prior DIABETES
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
ApoB/ApoA1 ratio &
diabetes
(10269)
(10267)
<1.0 mmol/L
Diabetes
301
382
(16.9%)
(21.6%)
No diabetes
717
899
(18.3%)
(22.9%) 
1.0 mmol/L
300
366
(25.2%)
(30.1%)
715
937
(21.3%)
(27.9%)
ALL PATIENTS
2033
2585
(19.8%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events irrespective of various lipid or apolipoprotein ratios at baseline, both in those with and those without diabetes.

17. SIMVASTATIN: MAJOR VASCULAR EVENTS by DURATION OF DIABETES
Duration (years)
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better
PLACEBO better
<6
203
(18.9%)
247
(23.0%) 
6 <13
201
(20.8%)
241
(25.6%)  13
197
(21.0%)
259
(26.7%)
No diabetes
1432
(19.6%)
1837
(25.2%)
24% SE 3
ALL PATIENTS
2033
(19.8%)
2585
(25.2%)
Notes: There were similar proportional reductions in risk of major vascular events irrespective of the duration of diabetes.
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4

18. SIMVASTATIN: MAJOR VASCULAR EVENTS
by TYPE OF DIABETES
SIMVASTATIN
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
Type of
diabetes
(10269)
(10267)
Type 1 43 53
(13.7%)
(17.5%)
Type 2
558
695
(20.9%)
(25.9%)
No diabetes
1432
1837
(19.6%)
(25.2%)
ALL PATIENTS
2033
2585
(19.8%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events in those with type 1 as well as type 2 diabetes. However, with only 615 patients having type 1 diabetes, there were only small numbers suffering an event and the confidence intervals around the estimate are wide.

19. SIMVASTATIN: MAJOR VASCULAR EVENTS by HbA1c
PLACEBO
Rate ratio & 95% CI
STATIN better
PLACEBO better
HbA1c (%)
(10269)
(10267)
<7.0
294
360
(18.3%)
(22.6%) 
7.0
301
373
(27.5%)
No diabetes
1432
1837
(19.6%)
(25.2%)
ALL PATIENTS
2033
2585
(19.8%)
24% SE 3
reduction
(2P< )
0.4
0.6
0.8
1.0
1.2
1.4
Notes: There were similar proportional reductions in risk of major vascular events irrespective of the glycaemic control at entry among those with diagnosed diabetes.

20. SIMVASTATIN: HbA1c (% ± SE) among a sample with DIABETES at entry
Notes: HbA1C was measured at entry in those with diagnosed diabetes and in a random sample of 1087 after an average of 4.6 years of follow-up. There was no evidence that allocation to simvastatin had any effect on glycaemic control in these patients.

21. SIMVASTATIN: Development of DIABETES in patients not known to have diabetes at entry
Notes: There was no evidence that allocation to simvastatin reduced the incidence of new diabetes during the trial.

22. SIMVASTATIN: Change in blood CREATININE (µmol/l ± se) from baseline to 4 years
Notes: Creatinine was measured at baseline and in samples collected after an average of 4.6 years of follow-up. Plasma creatinine increased during follow-up, but the increase was significantly smaller among those allocated simvastatin compared with placebo.

23. HPS: Effects of SIMVASTATIN on first and all major vascular events in those with and without diabetes
Notes: Continued treatment reduced the rate not just of the first occurrence of a major vascular event but also of subsequent events. The absolute reductions in the number of major vascular events avoided per 1000 people are more than 50% greater than the number of people per 1000 who avoided such events, both among those with or without diabetes.

24. Occlusive arterial disease alone Both arterial disease and diabetes
Absolute effects of simvastatin allocation on 5-year rates of first major vascular event
Risk reductions (SE):
Proportional
32.9% (9.1)
24.5% (3.1)
18.4% (5.7)
Absolute/1000
44 (12)
62 (8)
66 (21)
P-value
0.0003
<0.0001
0.002 40
Diabetes alone
Occlusive arterial disease alone
Both arterial disease and diabetes 9%
13%
20%
25%
31%
36% S P 30 20 10
S=simvastatin-allocated P=placebo-allocated
Proportion with first major vascular event (%)
Notes: Similar proportional benefits were observed with allocation to simvastatin among people in different baseline disease categories. The larger absolute benefit seen among participants with diabetes alone may reflect the play of chance on the proportional reduction observed just in that relatively small subgroup. By contrast, estimates of the absolute benefit derived from the more reliably determined overall reduction of one quarter, would suggest that a 1 mmol/L LDL reduction would produce an absolute risk reduction of 30 per 1000 in patients with diabetes alone.

25. HPS: Conclusions for people with diabetes
Lowering LDL cholesterol by 1 mmol/L (40 mg/dL) reduces the risk of major vascular events by about one-quarter during 5 years of treatment
Similar proportional reductions in risk among people with or without diabetes ― irrespective of age, sex, vascular disease or lipid levels
Continued statin treatment prevents not only first but also subsequent major vascular events
Notes: none