Baseline characteristics of HPS participants
by prior diabetes
Diabetes
(5963)
No diabetes
(14 573)
62.1
64.7
4147 (70%)
758 (13%)
11 307 (78%)
2155 (15%)
Vascular disease
Prior MI
1125 (19%)
7385 (51%)
Age (years)
Men
Current smoker
Other CHD
Other vascular
No vascular
856 (14%)
4020 (28%)
1070 (18%)
2912 (49%)
2930 (20%)
238 (2%)
HPS: Baseline lipids (mmol/L) and
apolipoproteins (g/L) by prior diabetes
Diabetes
(5963)
No diabetes
(14 573)
Total cholesterol
LDL
HDL
Triglycerides
5.7
3.2
1.06
2.3
5.9
3.4
1.06
2.0
Apo A1
1.20
1.20
Apo B
1.10
1.16
HPS: Baseline lipids (mg/dL) and
apolipoproteins (g/L) by prior diabetes
Diabetes
(5963)
No diabetes
(14 573)
Total cholesterol
221
228
LDL
HDL
Triglycerides
124
41
204
132
41
177
Apo A1
1.20
1.20
Apo B
1.10
1.16
HPS: FACTORIAL TREATMENT COMPARISONS
Simvastatin
(40 mg daily)
vs
Placebo
tablets
Vitamins
(600 mg E, 250 mg C
& 20 mg beta-carotene)
vs
Placebo
capsules
5 years average duration of follow-up
HPS: Mean (SE) differences in lipids during
follow-up by diabetes
Lipids (mmol/L)
& Apos (g/L)
Diabetes
(5963)
Total cholesterol -1.1
(0.04)
No diabetes
(14 573)
-1.2
(0.02)
LDL
HDL
Triglycerides
-0.9 (0.03)
0.01 (0.01)
-0.3 (0.06)
-1.0
(0.02)
0.04 (0.01)
-0.3
(0.03)
Apo A1
-0.011 (0.019)
0.016 (0.007)
Apo B
-0.263 (0.020)
-0.289 (0.010)
SIMVASTATIN: MAJOR CORONARY EVENTS
and STROKE by prior DIABETES
Vascular event
& disease group
SIMVASTATIN PLACEBO
(10269)
(10267)
Major coronary events
Diabetes
279 (9.4%)
377 (12.6%)
No diabetes
619 (8.5%)
835 (11.5%)
All patients
898 (8.7%)
1212 (11.8%)
Diabetes
149 (5.0%)
193 (6.5%)
No diabetes
295 (4.0%)
392 (5.4%)
All patients
444 (4.3%)
585 (5.7%)
Rate ratio & 95% CI
STATIN better PLACEBO better
27% SE 4
reduction
(2P<0.00001)
Strokes
0.4
25% SE 5
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: REVASCULARISATIONS and
MAJOR VASCULAR EVENTS by prior DIABETES
Vascular event
& disease group
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
Revascularisations
Diabetes
260 (8.7%)
309 (10.4%)
No diabetes
679 (9.3%)
896 (12.3%)
All patients
939 (9.1%)
1205 (11.7%)
601 (20.2%)
748 (25.1%)
24% SE 4
reduction
(2P<0.00001)
Major vascular events
Diabetes
No diabetes
1432 (19.6%) 1837 (25.2%)
ALL PATIENTS
2033 (19.8%) 2585 (25.2%)
0.4
24% SE 3
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENT by YEAR
in DIABETIC PATIENTS
Year
of follow-up
1
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(2978)
(2985)
STATIN better PLACEBO better
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%)
601 (20.2%)
748 (25.1%)
ALL FOLLOW-UP
0.4
22% SE 5
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS by YEAR
in DIABETIC PATIENTS
30
Logrank p<0.00001
People suffering events (%)
25
PLACEBO
20
15
SIMVASTATIN
10
5
0
0
1
2
3
4
5
47(10)
51(15)
6
Years of follow-up
Benefit/1000(SE)
-1(6)
13(8)
34(9)
58(48)
SIMVASTATIN: MAJOR VASCULAR EVENTS
by PRIOR DISEASE & prior DIABETES
Prior disease &
diabetes
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
CHD
Diabetes
No diabetes
325 (33.4%)
381 (37.8%)
1134 (19.8%) 1460 (25.7%)
Other CVD
Diabetes
141 (25.6%)
171 (32.9%)
No diabetes
287 (19.8%)
362 (24.4%)
135 (9.3%)
196 (13.5%)
No CVD
Diabetes
ALL PATIENTS
24% SE 3
reduction
(2P<0.00001)
2033 (19.8%) 2585 (25.2%)
0.4
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS
by SEX & prior DIABETES
Sex &
diabetes
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
Male
Diabetes
No diabetes
471 (22.8%)
580 (27.8%)
1195 (21.1%) 1555 (27.6%)
Female
Diabetes
130 (14.2%)
168 (18.6%)
No diabetes
237 (14.6%)
282 (17.2%)
ALL PATIENTS
24% SE 3
reduction
(2P<0.00001)
2033 (19.8%) 2585 (25.2%)
0.4
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS
by AGE & prior DIABETES
Age &
diabetes
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
<65 y
Diabetes
263 (15.7%)
341 (20.1%)
No diabetes
568 (17.6%)
750 (23.1%)
Diabetes
338 (25.9%)
407 (31.6%)
No diabetes
864 (21.3%) 1087 (26.9%)
ALL PATIENTS
2033 (19.8%) 2585 (25.2%)
65 y
0.4
24% SE 3
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS
by LDL CHOLESTEROL & prior DIABETES
LDL cholesterol &
diabetes
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
<3.0 mmol/L
Diabetes
191 (15.7%)
252 (20.9%)
No diabetes
407 (18.8%)
504 (22.9%)
410 (23.3%)
496 (27.9%)
3.0 mmol/L
Diabetes
No diabetes
1025 (20.0%) 1333 (26.2%)
ALL PATIENTS
2033 (19.8%) 2585 (25.2%)
0.4
24% SE 3
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS
by TRIGLYCERIDES & prior DIABETES
Triglycerides &
diabetes
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
<2.0 mmol/L
Diabetes
270 (16.8%)
364 (22.8%)
No diabetes
831 (18.9%) 1068 (24.1%)
2.0 mmol/L
Diabetes
331 (24.1%)
384 (27.6%)
No diabetes
601 (20.8%)
769 (27.1%)
ALL PATIENTS
24% SE 3
reduction
(2P<0.00001)
2033 (19.8%) 2585 (25.2%)
0.4
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS
by HDL CHOLESTEROL & prior DIABETES
HDL cholesterol &
diabetes
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
<0.9 mmol/L
Diabetes
288 (25.9%)
356 (31.1%)
No diabetes
530 (21.1%)
708 (29.3%)
Diabetes
313 (16.8%)
392 (21.3%)
No diabetes
902 (18.9%) 1129 (23.2%)
ALL PATIENTS
2033 (19.8%) 2585 (25.2%)
0.9 mmol/L
0.4
24% SE 3
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS
by ApoB/ApoA1 ratio & prior DIABETES
ApoB/ApoA1 ratio &
diabetes
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
<1.0 mmol/L
Diabetes
301 (16.9%)
382 (21.6%)
No diabetes
717 (18.3%)
899 (22.9%)
Diabetes
300 (25.2%)
366 (30.1%)
No diabetes
715 (21.3%)
937 (27.9%)
1.0 mmol/L
ALL PATIENTS
24% SE 3
reduction
(2P<0.00001)
2033 (19.8%) 2585 (25.2%)
0.4
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS
by DURATION OF DIABETES
Duration (years)
<6
6 <13
13
SIMVASTATIN PLACEBO
(10269)
(10267)
203 (18.9%)
247 (23.0%)
201 (20.8%)
241 (25.6%)
197 (21.0%)
259 (26.7%)
No diabetes
1432 (19.6%) 1837 (25.2%)
ALL PATIENTS
2033 (19.8%) 2585 (25.2%)
0.4
Rate ratio & 95% CI
STATIN better PLACEBO better
24% SE 3
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS
by TYPE OF DIABETES
Type of
diabetes
SIMVASTATIN PLACEBO
(10269)
(10267)
Type 1
43 (13.7%)
53 (17.5%)
Type 2
558 (20.9%)
695 (25.9%)
No diabetes
1432 (19.6%) 1837 (25.2%)
ALL PATIENTS
2033 (19.8%) 2585 (25.2%)
0.4
Rate ratio & 95% CI
STATIN better PLACEBO better
24% SE 3
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: MAJOR VASCULAR EVENTS by HbA1c
HbA1c (%)
SIMVASTATIN PLACEBO
(10269)
(10267)
<7.0
294 (18.3%)
360 (22.6%)
7.0
301 (22.6%)
373 (27.5%)
No diabetes
1432 (19.6%) 1837 (25.2%)
ALL PATIENTS
2033 (19.8%) 2585 (25.2%)
0.4
Rate ratio & 95% CI
STATIN better PLACEBO better
24% SE 3
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
SIMVASTATIN: HbA1c (% ± SE) among
a sample with DIABETES at entry
Assessment
SIMVASTATIN
(562)
PLACEBO
(525)
Baseline
6.99 ± 0.11
7.06 ± 0.10
Follow-up
7.14 ± 0.06
7.17 ± 0.06
Change
0.15 ± 0.09
0.12 ± 0.09
Difference
-0.03 ± 0.13 (NS)
SIMVASTATIN: Development of DIABETES in
patients not known to have diabetes at entry
Evidence
for diabetes
Reported
Oral hypoglycaemic
Insulin use
ANY OF ABOVE
SIMVASTATIN PLACEBO
(7291)
(7282)
219
225
23
206
186
27
335
(4.6%)
293
(4.0%)
NS
SIMVASTATIN: Change in blood CREATININE
(µmol/l ± se) from baseline to 4 years
Baseline
disease
STATIN
Diabetes
10.7 ± 0.5
12.9 ± 0.7
2.2 ± 0.9
No diabetes
5.7 ± 0.3
7.4 ± 0.4
1.7 ± 0.4
ALL PATIENTS
7.1 ± 0.2
8.9 ± 0.3
1.8 ± 0.4
PLACEBO
2P<0.00001
Difference
HPS: Effects of SIMVASTATIN on first and all major
vascular events in those with and without diabetes
Previous disease
at entry
Simvastatin Placebo Events (SE)
(10,269)
(10,267) avoided/1000
allocated Simv
Diabetes
First events
All events
601
852
748
1109
49 (11)
85 (19)
No diabetes
First event
All events
1432
1911
1837
2588
56 (7)
93 (11)
ALL PATIENTS
First event
All events
2033
2763
2585
3697
54 (6)
91 (10)
Absolute effects of simvastatin allocation on
5-year rates of first major vascular event
Risk reductions (SE):
Proportional
Absolute/1000
P-value
32.9% (9.1)
44 (12)
0.0003
24.5% (3.1)
62 (8)
<0.0001
18.4% (5.7)
66 (21)
0.002
40
Proportion with first major
vascular event (%)
P
30
S=simvastatin-allocated
P=placebo-allocated
S
P
S
20
P
10
S
9% 13%
20% 25%
31% 36%
Diabetes
alone
Occlusive arterial
disease alone
Both arterial
disease and
diabetes
0
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