Baseline characteristics of HPS participants by prior cerebrovascular disease

Baseline lipids (mmol/L) and apolipoproteins (g/L) by prior cerebrovascular disease

Baseline lipids (mg/dL) and apolipoproteins (g/L) by prior cerebrovascular disease

FACTORIAL TREATMENT COMPARISONS

(10269)(10267) SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Type Ischaemic 5153 Haemorrhagic Unknown Severity Fatal 4251 Severe Moderate Mild 6171 Unknown (4.3%)(5.7%) 25% SE 5 reduction (2P< ) ALL STROKES HPS: Stroke Incidence

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) Age (years) < (3.3%)(4.0%) ≥ 65 < (4.5%)(6.3%) ≥ (5.8%)(8.2%) Sex Male331453(4.3%)(5.9%) Female113132(4.4%)(5.2%) ALL PATIENTS444585(4.3%)(5.7%) 25% SE 5 reduction (2P< ) HPS: STROKE incidence by AGE & SEX

(10269)(10267) SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature Age (16.9%)(22.1%)< (20.9%)(27.2%) (23.8%)(27.7%) (23.1%)(32.3%)  75 Sex (21.6%)(27.6%)Male (14.4%)(17.7%)Female 24% SE 3 reduction (2P< ) (19.8%)(25.2%)ALL PATIENTS HPS: MAJOR VASCULAR EVENT by AGE & SEX

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) Prior coronary disease Yes265347(4.0%)(5.2%) No179238(5.0%)(6.7%) Prior cerebrovascular disease Yes169170(10.3%)(10.4%) No275415(3.2%)(4.8%) Prior diabetes Yes149193(5.0%)(6.5%) No295392(4.0%)(5.4%) ALL PATIENTS444585(4.3%)(5.7%) 25% SE 5 reduction (2P< ) HPS: STROKE by PRIOR DISEASE

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) Prior coronary disease Yes175237(2.6%)(3.5%) No115172(3.2%)(4.8%) Prior cerebrovascular disease Yes100122(6.1%)(7.5%) No190287(2.2%)(3.3%) Prior diabetes Yes102140(3.4%)(4.7%) No188269(2.6%)(3.7%) ALL PATIENTS290409(2.8%)(4.0%) 30% SE 6 reduction (2P< wœ4õ) HPS: ISCHAEMIC STROKE by PRIOR DISEASE

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) Prior coronary disease Yes (21.8%)(27.5%) No574744(16.1%)(20.8%) Prior cerebrovascular disease Yes406488(24.7%)(29.8%) No (18.9%)(24.3%) Prior diabetes Yes601748(20.2%)(25.1%) No (19.6%)(25.2%) ALL PATIENTS (19.8%)(25.2%) 24% SE 3 reduction (2P< ) HPS: MAJOR VASCULAR EVENTS by PRIOR DISEASE

Absolute effects on major vascular events and strokes subdivided by prior cerebrovascular disease S S P P Yes No Prior cerebrovascular disease Major vascular event (%) Risk reductions (SE): Proportional Absolute/1000 P-value 20% (6) 58 (18) p= % (3) 60 (7) p< Other event Stroke

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) LDL cholesterol (mmol/L) < (4.0%)(5.7%) ≥ 3.0 < (4.2%)(6.2%) > (4.6%)(5.4%) HDL cholesterol (mmol/L) < (4.7%)(5.6%) ≥ 0.9 < (4.1%)(5.8%) > (4.1%)(5.7%) ALL PATIENTS444585(4.3%)(5.7%) 25% SE 5 reduction (2P< ) HPS: STROKE incidence by BASELINE LIPIDS

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) LDL cholesterol (mmol/L) < (17.6%)(22.2%) ≥ 3.0 < (19.0%)(25.7%) > (22.0%)(27.2%) HDL cholesterol (mmol/L) < (22.6%)(29.9%) ≥ 0.9 < (20.0%)(25.1%) > (17.0%)(20.9%) ALL PATIENTS (19.8%)(25.2%) 24% SE 3 reduction (2P< ) HPS: MAJOR VASCULAR EVENTS by BASELINE LIPIDS

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) Diastolic blood pressure (mmHg) < (3.9%)(5.2%) ≥ 80 < (4.0%)(5.8%) ≥ (5.6%)(6.5%) Systolic blood pressure (mmHg) < (3.6%)(4.2%) ≥ 140 < (3.9%)(5.3%) ≥ (6.1%)(8.8%) ALL PATIENTS444585(4.3%)(5.7%) 25% SE 5 reduction (2P< ) HPS: STROKE incidence by baseline BLOOD PRESSURE

(10269)(10267) SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature DBP (mmHg) (20.4%)(26.4%)< (19.5%)(23.5%)  80 < (19.2%)(25.1%)  90 SBP (mmHg) (19.4%)(23.5%)< (17.9%)(24.4%)  140 < (22.7%)(29.2%)  % SE 3 reduction (2P< ) (19.8%)(25.2%)ALL PATIENTS HPS: MAJOR VASCULAR EVENTS by baseline BLOOD PRESSURE

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) Treated hypertension Yes223274(5.3%)(6.5%) No221311(3.6%)(5.2%) Aspirin Yes286378(4.4%)(5.8%) No158207(4.2%)(5.5%) ALL PATIENTS444585(4.3%)(5.7%) 25% SE 5 reduction (2P< ) HPS: STROKE incidence by TREATED HYPERTENSION and ASPIRIN USE

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) Treated hypertension Yes (22.4%)(28.1%) No (18.0%)(23.1%) Aspirin Yes (21.1%)(27.4%) No663801(17.5%)(21.3%) ALL PATIENTS (19.8%)(25.2%) 24% SE 3 reduction (2P< ) HPS: MAJOR VASCULAR EVENTS by TREATED HYPERTENSION & ASPIRIN USE

SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Year of follow-up (10269)(10267) (0.8%)(1.0%) (0.8%)(1.3%) (0.8%)(1.2%) (0.9%)(1.2%) (1.2%)(1.4%) ALL PATIENTS444585(4.3%)(5.7%) 25% SE 5 reduction (2P< ) 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< Proportion with stroke HPS: STROKE by YEAR

STATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Study GREACE917(1.1%)(2.1%) AFCAPS/TexcAPS1417(0.4%)(0.5%) Post-CABG1816(2.7%)(2.4%) GISSI2019(0.9%) WOSCOPS4651(1.4%)(1.5%) CARE5276(2.5%)(3.7%) SSSS5676(2.5%)(3.4%) ASCOT89121(1.7%)(2.4%) PROSPER135131(4.7%)(4.5%) LIPID169204(3.7%)(4.5%) ALLHAT209231(4.0%)(4.5%) HPS444585(4.3%)(5.7%) ALL PATIENTS (3.0%)(3.6%) 21% SE 4 reduction (2P< ) 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