baseline characteristics of hps participants by prior cerebrovascular disease
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Baseline characteristics of HPS participantsby prior cerebrovascular disease
Cerebrovascular disease (3280)
No cerebrovascular disease (17 256)
Age (years) 65.5 63.7
Men 2445 (75%) 13 009 (75%)
Current smoker 534 (16%) 2379 (14%)
Coronary disease Prior MI 896 (27%) 7614 (44%)
Other CHD 564 (17%) 4312 (25%)
None 1820 (55%) 5330 (31%)
Hypertension 1655 (50%) 6802 (39%)
Baseline lipids (mmol/L) and apolipoproteins (g/L) by prior cerebrovascular disease
Cerebrovascular disease (3280)
No cerebrovascular disease (17 256)
Total cholesterol 5.9 5.8
LDL 3.4 3.4
HDL 1.08 1.05
Triglycerides 2.1 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 disease (3280)
No cerebrovascular disease (17 256)
Total cholesterol 228 225
LDL 132 132
HDL 42 41
Triglycerides 189 189
Apo A1 1.21 1.20
Apo B 1.16 1.14
Simvastatin(40 mg daily)
vs Placebotablets
Vitamins(600 mg E, 250 mg C& 20 mg beta-carotene)
vs Placebocapsules
5 years average duration of follow-up
FACTORIAL TREATMENT COMPARISONS
(10269) (10267)
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Type
290 409Ischaemic51 53Haemorrhagic
103 134Unknown
Severity
96 119Fatal42 51Severe
107 155Moderate138 189Mild
61 71Unknown
(4.3%) (5.7%)25% SE 5reduction
444 585
(2P<0.00001)
ALL STROKES
0.4 0.6 0.8 1.0 1.2 1.4
HPS: Stroke Incidence
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Baselinefeature (10269) (10267)
Age (years)
< 65 164 195(3.3%) (4.0%)
≥ 65 < 70 110 154(4.5%) (6.3%)
≥ 70 170 236(5.8%) (8.2%)
Sex
Male 331 453(4.3%) (5.9%)
Female 113 132(4.4%) (5.2%)
ALL PATIENTS 444 585(4.3%) (5.7%)25% SE 5reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: STROKE incidence by AGE & SEX
(10269) (10267)
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Baselinefeature
Age
831 1091(16.9%) (22.1%)< 65
512 665(20.9%) (27.2%)65 - 69
548 620(23.8%) (27.7%)70 - 74
142 209(23.1%) (32.3%) 75
Sex
1666 2135(21.6%) (27.6%)Male
367 450(14.4%) (17.7%)Female
24% SE 3reduction(2P<0.00001)
2033 2585(19.8%) (25.2%)ALL PATIENTS
0.4 0.6 0.8 1.0 1.2 1.4
HPS: MAJOR VASCULAR EVENT by AGE & SEX
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Baselinefeature (10269) (10267)
Prior coronary disease
Yes 265 347(4.0%) (5.2%)
No 179 238(5.0%) (6.7%)
Prior cerebrovascular disease
Yes 169 170(10.3%) (10.4%)
No 275 415(3.2%) (4.8%)
Prior diabetes
Yes 149 193(5.0%) (6.5%)
No 295 392(4.0%) (5.4%)
ALL PATIENTS 444 585(4.3%) (5.7%)25% SE 5reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: STROKE by PRIOR DISEASE
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Baselinefeature (10269) (10267)
Prior coronary disease
Yes 175 237(2.6%) (3.5%)
No 115 172(3.2%) (4.8%)
Prior cerebrovascular disease
Yes 100 122(6.1%) (7.5%)
No 190 287(2.2%) (3.3%)
Prior diabetes
Yes 102 140(3.4%) (4.7%)
No 188 269(2.6%) (3.7%)
ALL PATIENTS 290 409(2.8%) (4.0%)30% SE 6reduction(2P<0.00001wœ4õ)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: ISCHAEMIC STROKE by PRIOR DISEASE
SIMVASTATIN PLACEBO Rate ratio & 95% CISTATIN better PLACEBO better
Baselinefeature (10269) (10267)
Prior coronary disease
Yes 1459 1841(21.8%) (27.5%)
No 574 744(16.1%) (20.8%)
Prior cerebrovascular disease
Yes 406 488(24.7%) (29.8%)
No 1627 2097(18.9%) (24.3%)
Prior diabetes
Yes 601 748(20.2%) (25.1%)
No 1432 1837(19.6%) (25.2%)
ALL PATIENTS 2033 2585(19.8%) (25.2%)24% SE 3reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: MAJOR VASCULAR EVENTS by PRIOR DISEASE
0
10
20
30
0
10
20
30
Absolute effects on major vascular events and strokes subdivided by prior cerebrovascular disease
S
S
P
P
Yes No
Prior cerebrovascular disease
Maj
or
vas
cula
r ev
ent
(%)
Risk reductions (SE):
ProportionalAbsolute/1000P-value
20% (6)58 (18)p=0.001
25% (3) 60 (7)
p<0.0001Other event
Stroke
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Baselinefeature (10269) (10267)
LDL cholesterol (mmol/L)
< 3.0 137 194(4.0%) (5.7%)
≥ 3.0 < 3.5 108 155(4.2%) (6.2%)
> 3.5 199 236(4.6%) (5.4%)
HDL cholesterol (mmol/L)
< 0.9 170 199(4.7%) (5.6%)
≥ 0.9 < 1.1 115 166(4.1%) (5.8%)
> 1.1 159 220(4.1%) (5.7%)
ALL PATIENTS 444 585(4.3%) (5.7%)25% SE 5reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: STROKE incidence by BASELINE LIPIDS
SIMVASTATIN PLACEBO Rate ratio & 95% CISTATIN better PLACEBO better
Baselinefeature (10269) (10267)
LDL cholesterol (mmol/L)
< 3.0 598 756(17.6%) (22.2%)
≥ 3.0 < 3.5 484 646(19.0%) (25.7%)
> 3.5 951 1183(22.0%) (27.2%)
HDL cholesterol (mmol/L)
< 0.9 818 1064(22.6%) (29.9%)
≥ 0.9 < 1.1 560 720(20.0%) (25.1%)
> 1.1 655 801(17.0%) (20.9%)
ALL PATIENTS 2033 2585(19.8%) (25.2%)24% SE 3reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: MAJOR VASCULAR EVENTS by BASELINE LIPIDS
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Baselinefeature (10269) (10267)
Diastolic blood pressure (mmHg)
< 80 176 239(3.9%) (5.2%)
≥ 80 < 90 131 185(4.0%) (5.8%)
≥ 90 137 160(5.6%) (6.5%)
Systolic blood pressure (mmHg)
< 140 162 189(3.6%) (4.2%)
≥ 140 < 160 121 169(3.9%) (5.3%)
≥ 160 161 226(6.1%) (8.8%)
ALL PATIENTS 444 585(4.3%) (5.7%)25% SE 5reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: STROKE incidence by baselineBLOOD PRESSURE
(10269) (10267)SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO betterBaselinefeature
DBP (mmHg)
917 1210(20.4%) (26.4%)< 80
644 753(19.5%) (23.5%) 80 < 90
472 621(19.2%) (25.1%) 90
SBP (mmHg)
880 1064(19.4%) (23.5%)< 140
553 772(17.9%) (24.4%) 140 < 160
600 748(22.7%) (29.2%) 160
24% SE 3reduction(2P<0.00001)
2033 2585(19.8%) (25.2%)ALL PATIENTS
0.4 0.6 0.8 1.0 1.2 1.4
HPS: MAJOR VASCULAR EVENTS by baselineBLOOD PRESSURE
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Baselinefeature (10269) (10267)
Treated hypertension
Yes 223 274(5.3%) (6.5%)
No 221 311(3.6%) (5.2%)
Aspirin
Yes 286 378(4.4%) (5.8%)
No 158 207(4.2%) (5.5%)
ALL PATIENTS 444 585(4.3%) (5.7%)25% SE 5reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: STROKE incidence by TREATED HYPERTENSION and ASPIRIN USE
SIMVASTATIN PLACEBO Rate ratio & 95% CISTATIN better PLACEBO better
Baselinefeature (10269) (10267)
Treated hypertension
Yes 942 1195(22.4%) (28.1%)
No 1091 1390(18.0%) (23.1%)
Aspirin
Yes 1370 1784(21.1%) (27.4%)
No 663 801(17.5%) (21.3%)
ALL PATIENTS 2033 2585(19.8%) (25.2%)24% SE 3reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS: MAJOR VASCULAR EVENTS by TREATED HYPERTENSION & ASPIRIN USE
SIMVASTATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Year offollow-up (10269) (10267)
1 87 106(0.8%) (1.0%)
2 81 132(0.8%) (1.3%)
3 82 111(0.8%) (1.2%)
4 81 111(0.9%) (1.2%)
5+ 113 125(1.2%) (1.4%)
ALL PATIENTS 444 585(4.3%) (5.7%)25% SE 5reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
HPS : STROKE incidence by YEAR
Years of follow-up
PLACEBO
SIMVASTATIN
Benefit/1000(SE) 2(1) 7(2) 10(2) 13(3) 14(4) 15(10)
Logrank p<0.0001
0 1 2 3 4 5 60
1
2
3
4
5
6
7P
ropo
rtio
n w
ith s
trok
eHPS: STROKE by YEAR
STATIN PLACEBO Rate ratio & 95% CI
STATIN better PLACEBO better
Study
GREACE 9 17(1.1%) (2.1%)
AFCAPS/TexcAPS 14 17(0.4%) (0.5%)
Post-CABG 18 16(2.7%) (2.4%)
GISSI 20 19(0.9%) (0.9%)
WOSCOPS 46 51(1.4%) (1.5%)
CARE 52 76(2.5%) (3.7%)
SSSS 56 76(2.5%) (3.4%)
ASCOT 89 121(1.7%) (2.4%)
PROSPER 135 131(4.7%) (4.5%)
LIPID 169 204(3.7%) (4.5%)
ALLHAT 209 231(4.0%) (4.5%)
HPS 444 585(4.3%) (5.7%)
ALL PATIENTS 1261 1544(3.0%) (3.6%)21% SE 4reduction(2P<0.00001)
0.4 0.6 0.8 1.0 1.2 1.4
Effects on STROKE in major STATIN trials
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
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