baseline characteristics of hps participants by prior diabetes

Baseline characteristics of HPS participants by prior diabetes

Diabetes (5963)

No diabetes (14 573)

Age (years) 62.1 64.7

Men 4147 (70%) 11 307 (78%)

Current smoker 758 (13%) 2155 (15%)

Vascular disease Prior MI 1125 (19%) 7385 (51%)

Other CHD 856 (14%) 4020 (28%)

Other vascular 1070 (18%) 2930 (20%)

No vascular 2912 (49%) 238 (2%)

HPS: Baseline lipids (mmol/L) and apolipoproteins (g/L) by prior diabetes

Diabetes (5963)


Total cholesterol 5.7 5.9

LDL 3.2 3.4

HDL 1.06 1.06

Triglycerides 2.3 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)


Total cholesterol 221 228

LDL 124 132

HDL 41 41

Triglycerides 204 177

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) -1.2 (0.02)

LDL -0.9 (0.03) -1.0 (0.02)

HDL 0.01 (0.01) 0.04 (0.01)

Triglycerides -0.3 (0.06) -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 EVENTSand STROKE by prior DIABETES

SIMVASTATIN PLACEBO Rate ratio & 95% CISTATIN 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 4reduction(2P<0.00001)

Strokes

Diabetes 149 193(5.0%) (6.5%)

No diabetes 295 392(4.0%) (5.4%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: REVASCULARISATIONS andMAJOR VASCULAR EVENTS by prior DIABETES


Vascular event& disease group (10269) (10267)

Revascularisations

Diabetes 260 309(8.7%) (10.4%)

No diabetes 679 896(9.3%) (12.3%)


Major vascular events

Diabetes 601 748(20.2%) (25.1%)

No diabetes 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

SIMVASTATIN: MAJOR VASCULAR EVENT by YEARin DIABETIC PATIENTS


Yearof follow-up (2978) (2985)

1 143 141(4.8%) (4.7%)

2 110 150(3.9%) (5.3%)

3 109 172(4.0%) (6.5%)

4 101 138(3.9%) (5.6%)

5+ 138 147(5.7%) (6.4%)

ALL FOLLOW-UP 601 748(20.2%) (25.1%)22% SE 5reduction(2P<0.00001)

0.4 0.6 0.8 1.0 1.2 1.4

Peo

ple

suffe

ring

even

ts (

%)

SIMVASTATIN: MAJOR VASCULAR EVENTS by YEARin 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<0.00001

0 1 2 3 4 5 60

5

10

15

20

25

30

SIMVASTATIN: MAJOR VASCULAR EVENTSby PRIOR DISEASE & prior DIABETES


Prior disease &diabetes (10269) (10267)

CHD

Diabetes 325 381(33.4%) (37.8%)

No diabetes 1134 1460(19.8%) (25.7%)

Other CVD

Diabetes 141 171(25.6%) (32.9%)

No diabetes 287 362(19.8%) (24.4%)

No CVD

Diabetes 135 196(9.3%) (13.5%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTSby SEX & prior DIABETES


Sex &diabetes (10269) (10267)

Male

Diabetes 471 580(22.8%) (27.8%)

No diabetes 1195 1555(21.1%) (27.6%)

Female

Diabetes 130 168(14.2%) (18.6%)

No diabetes 237 282(14.6%) (17.2%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTSby AGE & prior DIABETES


Age & diabetes (10269) (10267)

<65 y

Diabetes 263 341(15.7%) (20.1%)

No diabetes 568 750(17.6%) (23.1%)

65 y

Diabetes 338 407(25.9%) (31.6%)

No diabetes 864 1087(21.3%) (26.9%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTSby LDL CHOLESTEROL & prior DIABETES


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

Diabetes 410 496(23.3%) (27.9%)

No diabetes 1025 1333(20.0%) (26.2%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTSby TRIGLYCERIDES & prior DIABETES


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

Diabetes 331 384(24.1%) (27.6%)

No diabetes 601 769(20.8%) (27.1%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTSby HDL CHOLESTEROL & prior DIABETES


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

Diabetes 313 392(16.8%) (21.3%)

No diabetes 902 1129(18.9%) (23.2%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTSby ApoB/ApoA1 ratio & prior DIABETES


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

Diabetes 300 366(25.2%) (30.1%)

No diabetes 715 937(21.3%) (27.9%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTSby DURATION OF DIABETES


Duration (years) (10269) (10267)

<6 203 247(18.9%) (23.0%)

6 <13 201 241(20.8%) (25.6%)

13 197 259(21.0%) (26.7%)

No diabetes 1432 1837(19.6%) (25.2%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTSby TYPE OF DIABETES


Type ofdiabetes (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%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: MAJOR VASCULAR EVENTS by HbA1c

SIMVASTATIN PLACEBO Rate ratio & 95% CI

STATIN better PLACEBO better

HbA1c (%) (10269) (10267)

<7.0 294 360(18.3%) (22.6%)

7.0 301 373(22.6%) (27.5%)

No diabetes 1432 1837(19.6%) (25.2%)


0.4 0.6 0.8 1.0 1.2 1.4

SIMVASTATIN: HbA1c (% ± SE) amonga 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

SIMVASTATIN (7291)

PLACEBO (7282)

Reported 219 206 Oral hypoglycaemic 225 186 Insulin use 23 27 ANY OF ABOVE 335 293 (4.6%) (4.0%)

NS

SIMVASTATIN: Change in blood CREATININE (µmol/l ± se) from baseline to 4 years

Baseline disease

STATIN PLACEBO Difference

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 2P<0.00001

HPS: Effects of SIMVASTATIN on first and all major vascular events in those with and without diabetes

Previous disease at entry

Simvastatin (10,269)

Placebo (10,267)

Events (SE) avoided/1000 allocated Simv

Diabetes First events

601

748

49 (11)

All events 852 1109 85 (19)

No diabetes First event

1432

1837

56 (7)

All events

1911 2588 93 (11)

ALL PATIENTS First event

2033

2585

54 (6)

All events 2763 3697 91 (10)

Proportional

Risk reductions (SE):

Absolute/1000P-value

Absolute effects of simvastatin allocation on 5-year rates of first major vascular event

40

Diabetesalone

Occlusive arterial disease alone

Both arterial disease and

diabetes

9% 13% 20% 25% 31% 36%

S

S

S

P

P

P

30

20

10

0

Pro

po

rtio

n w

ith

fir

st m

ajo

r va

scu

lar

eve

nt

(%)

32.9% (9.1)44 (12)0.0003

24.5% (3.1) 62 (8)

<0.0001

18.4% (5.7)66 (21)0.002

S=simvastatin-allocated P=placebo-allocated

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

baseline characteristics of hps participants by prior diabetes

Documents

risk of major vascular

events se avoided1000

baseline lipids mmoll

baseline lipids mgdl

development of diabetes

mean se differences

se amonga sample

blood creatinine moll