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Baseline characteristics of HPS participants
by prior cerebrovascular disease
Cerebrovascular No cerebrovascular
disease
disease
(3280)
(17 256)
Age (years)
Men
Current smoker
Coronary disease
Prior MI
65.5
2445 (75%)
534 (16%)
63.7
13 009 (75%)
2379 (14%)
896 (27%)
7614 (44%)
Other CHD
564 (17%)
4312 (25%)
None
Hypertension
1820 (55%)
1655 (50%)
5330 (31%)
6802 (39%)
Baseline lipids (mmol/L) and apolipoproteins (g/L)
by prior cerebrovascular disease
Cerebrovascular No cerebrovascular
disease
disease
(3280)
(17 256)
Total cholesterol
LDL
HDL
Triglycerides
5.9
3.4
1.08
2.1
5.8
3.4
1.05
2.1
Apo A1
1.21
1.20
Apo B
1.16
1.14
Baseline lipids (mg/dL) and apolipoproteins (g/L) by
prior cerebrovascular disease
Cerebrovascular No cerebrovascular
disease
disease
(3280)
(17 256)
Total cholesterol
LDL
HDL
Triglycerides
228
132
42
189
225
132
41
189
Apo A1
1.21
1.20
Apo B
1.16
1.14
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: STROKE INCIDENCE
SIMVASTATIN PLACEBO
(10269)
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
Type
Ischaemic
Haemorrhagic
Unknown
290
51
103
409
53
134
96
42
107
138
61
119
51
155
189
71
444
(4.3%)
585
(5.7%)
Severity
Fatal
Severe
Moderate
Mild
Unknown
ALL STROKES
25% SE 5
reduction
(2P<0.00001)
0.4
0.6
0.8
1.0
1.2
1.4
HPS: STROKE incidence by AGE & SEX
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
Age (years)
< 65
164 (3.3%)
195 (4.0%)
≥ 65 < 70
110 (4.5%)
154 (6.3%)
≥ 70
170 (5.8%)
236 (8.2%)
Male
331 (4.3%)
453 (5.9%)
Female
113 (4.4%)
132 (5.2%)
444 (4.3%)
585 (5.7%)
Sex
ALL PATIENTS
0.4
25% SE 5
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
HPS: MAJOR VASCULAR EVENT by AGE & SEX
Baseline
feature
SIMVASTATIN
(10269)
PLACEBO
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
Age
< 65
831 (16.9%) 1091 (22.1%)
65 - 69
512 (20.9%)
665 (27.2%)
70 - 74
548 (23.8%)
620 (27.7%)
 75
142 (23.1%)
209 (32.3%)
Sex
Male
Female
ALL PATIENTS
1666 (21.6%) 2135 (27.6%)
367 (14.4%)
450 (17.7%)
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
HPS: STROKE by PRIOR DISEASE
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
Prior coronary disease
Yes
265 (4.0%)
347 (5.2%)
No
179 (5.0%)
238 (6.7%)
Prior cerebrovascular disease
Yes
169 (10.3%)
170 (10.4%)
No
275 (3.2%)
415 (4.8%)
Yes
149 (5.0%)
193 (6.5%)
No
295 (4.0%)
392 (5.4%)
444 (4.3%)
585 (5.7%)
Prior diabetes
ALL PATIENTS
0.4
25% SE 5
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
HPS: ISCHAEMIC STROKE by PRIOR DISEASE
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
Prior coronary disease
Yes
175 (2.6%)
237 (3.5%)
No
115 (3.2%)
172 (4.8%)
Prior cerebrovascular disease
Yes
100 (6.1%)
122 (7.5%)
No
190 (2.2%)
287 (3.3%)
Yes
102 (3.4%)
140 (4.7%)
No
188 (2.6%)
269 (3.7%)
290 (2.8%)
409 (4.0%)
Prior diabetes
ALL PATIENTS
0.4
30% SE 6
reduction
(2P<0.00001wœ4õ)
0.6
0.8
1.0
1.2
1.4
HPS: MAJOR VASCULAR EVENTS by PRIOR DISEASE
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
Prior coronary disease
Yes
No
1459 (21.8%) 1841 (27.5%)
574 (16.1%)
744 (20.8%)
Prior cerebrovascular disease
Yes
No
406 (24.7%)
488 (29.8%)
1627 (18.9%) 2097 (24.3%)
Prior diabetes
Yes
No
ALL PATIENTS
601 (20.2%)
748 (25.1%)
1432 (19.6%) 1837 (25.2%)
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
Absolute effects on major vascular events and
strokes subdivided by prior cerebrovascular disease
Major vascular event (%)
Risk reductions (SE):
Proportional
Absolute/1000
P-value
20% (6)
58 (18)
p=0.001
25% (3)
60 (7)
p<0.0001
Other event
P
30
S
P
S
20
10
0
Yes
No
Prior cerebrovascular disease
Stroke
HPS: STROKE incidence by BASELINE LIPIDS
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
LDL cholesterol (mmol/L)
< 3.0
137 (4.0%)
194 (5.7%)
≥ 3.0 < 3.5
108 (4.2%)
155 (6.2%)
> 3.5
199 (4.6%)
236 (5.4%)
HDL cholesterol (mmol/L)
< 0.9
170 (4.7%)
199 (5.6%)
≥ 0.9 < 1.1
115 (4.1%)
166 (5.8%)
> 1.1
159 (4.1%)
220 (5.7%)
444 (4.3%)
585 (5.7%)
ALL PATIENTS
0.4
25% SE 5
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
HPS: MAJOR VASCULAR EVENTS by BASELINE LIPIDS
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
LDL cholesterol (mmol/L)
< 3.0
598 (17.6%)
756 (22.2%)
≥ 3.0 < 3.5
484 (19.0%)
646 (25.7%)
> 3.5
951 (22.0%) 1183 (27.2%)
HDL cholesterol (mmol/L)
< 0.9
818 (22.6%) 1064 (29.9%)
≥ 0.9 < 1.1
560 (20.0%)
720 (25.1%)
> 1.1
655 (17.0%)
801 (20.9%)
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
HPS: STROKE incidence by baseline
BLOOD PRESSURE
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
Diastolic blood pressure (mmHg)
< 80
176 (3.9%)
239 (5.2%)
≥ 80 < 90
131 (4.0%)
185 (5.8%)
≥ 90
137 (5.6%)
160 (6.5%)
Systolic blood pressure (mmHg)
< 140
162 (3.6%)
189 (4.2%)
≥ 140 < 160
121 (3.9%)
169 (5.3%)
≥ 160
161 (6.1%)
226 (8.8%)
444 (4.3%)
585 (5.7%)
ALL PATIENTS
0.4
25% SE 5
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
HPS: MAJOR VASCULAR EVENTS by baseline
BLOOD PRESSURE
Baseline
feature
SIMVASTATIN
(10269)
PLACEBO
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
DBP (mmHg)
< 80
917 (20.4%) 1210 (26.4%)
 80 < 90
644 (19.5%)
753 (23.5%)
 90
472 (19.2%)
621 (25.1%)
SBP (mmHg)
< 140
880 (19.4%) 1064 (23.5%)
 140 < 160
553 (17.9%)
772 (24.4%)
 160
600 (22.7%)
748 (29.2%)
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
HPS: STROKE incidence by
TREATED HYPERTENSION and ASPIRIN USE
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
Treated hypertension
Yes
223 (5.3%)
274 (6.5%)
No
221 (3.6%)
311 (5.2%)
Yes
286 (4.4%)
378 (5.8%)
No
158 (4.2%)
207 (5.5%)
444 (4.3%)
585 (5.7%)
Aspirin
ALL PATIENTS
0.4
25% SE 5
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
HPS: MAJOR VASCULAR EVENTS by TREATED
HYPERTENSION & ASPIRIN USE
Baseline
feature
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
Treated hypertension
Yes
942 (22.4%) 1195 (28.1%)
No
1091 (18.0%) 1390 (23.1%)
Aspirin
Yes
No
ALL PATIENTS
1370 (21.1%) 1784 (27.4%)
663 (17.5%)
801 (21.3%)
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
HPS : STROKE incidence by YEAR
Year of
follow-up
1
SIMVASTATIN PLACEBO
Rate ratio & 95% CI
(10269)
(10267)
STATIN better PLACEBO better
87 (0.8%)
106 (1.0%)
2
81 (0.8%)
132 (1.3%)
3
82 (0.8%)
111 (1.2%)
4
81 (0.9%)
111 (1.2%)
5+
113 (1.2%)
125 (1.4%)
444 (4.3%)
585 (5.7%)
ALL PATIENTS
0.4
25% SE 5
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
HPS: STROKE by YEAR
7
6
Logrank p<0.0001
PLACEBO
Proportion with stroke
5
4
3
SIMVASTATIN
2
1
0
0
1
2
3
4
5
13(3)
14(4)
6
Years of follow-up
Benefit/1000(SE)
2(1)
7(2)
10(2)
15(10)
Effects on STROKE in major randomised STATIN trials
Study
GREACE
STATIN
PLACEBO
9 (1.1%)
17 (2.1%)
AFCAPS/TexcAPS
14 (0.4%)
17 (0.5%)
Post-CABG
18 (2.7%)
16 (2.4%)
GISSI
20 (0.9%)
19 (0.9%)
WOSCOPS
46 (1.4%)
51 (1.5%)
CARE
52 (2.5%)
76 (3.7%)
SSSS
56 (2.5%)
76 (3.4%)
ASCOT
89 (1.7%)
121 (2.4%)
PROSPER
135 (4.7%)
131 (4.5%)
LIPID
169 (3.7%)
204 (4.5%)
ALLHAT
209 (4.0%)
231 (4.5%)
HPS
444 (4.3%)
585 (5.7%)
1261 (3.0%)
1544 (3.6%)
ALL PATIENTS
0.4
Rate ratio & 95% CI
STATIN better PLACEBO better
21% SE 4
reduction
(2P<0.00001)
0.6
0.8
1.0
1.2
1.4
HPS: Conclusions for people with
cerebrovascular disease
• Lowering LDL cholesterol by 1 mmol/L (40 mg/dL) reduces
the 5-year risk of ischaemic stroke by about one-quarter,
with no apparent adverse effect on cerebral haemorrhage
• Similar proportional reductions in stroke risk are seen with
statin therapy irrespective of age, sex, lipid levels, blood
pressure, or use of other medications (including aspirin)
• Statin therapy clearly reduces the risk of major vascular
events among people with pre-existing cerebrovascular
disease, irrespective of the presence of coronary disease