Economic evaluation of MRC/BHF Heart Protection Study

Heart Protection Study Collaborative GroupUniversity of Oxford

UK

HPS: Eligibility criteria• Increased risk of CHD death due to prior disease:

Myocardial infarction or other CHD;Occlusive disease of non-coronary arteries; orDiabetes mellitus or treated hypertension

• Age 40-80 years

• Total cholesterol 3.5 mmol/l ( 135mg/dl)

• Statin or vitamins not considered clearly indicated or contraindicated by patient’s own doctors

Cost-effectiveness analysis of allocation to 40mg daily simvastatin

• Based on within trial period only (mean 5 years)

• Costs for UK National Health Service (2001)

• Cost-effectiveness analyses undertaken:– per major vascular event* avoided– per vascular death avoided– overall and in subgroups at differing absolute risk

*first or subsequent heart attack, stroke or revascularisation following randomisation

Major vascular events (MVE) and vascular deaths per 1000 patients

Simvastatin

allocated

Placebo

allocated

Avoided per

1000 (SE)

All MVE 270 359 89 (10)

Vasculardeath

76 91 15 (4)

HPS: Methods of calculating costs

Costs included• Study simvastatin (40mg daily at £1/day) and

any non-study statin • Hospitalisations for all major and other

vascular events

Costs excluded• Non-statin drugs • Hospitalisations for non-vascular events

(no significant differences between groups)• Primary and social care costs

(no data available in HPS)

Mean costs per patient for statin use and hospitalisation for any vascular event

Cost category

Simvastatin

(n = 10,269)

Placebo

(n = 10,267)

Difference (SE)

Statin use £1,712 £215 £1,497 (8)

Vascular events

£1,819 £2,319 -£500 (78)

Total £3,530 £2,534 £996 (79)

Cost per MVE avoided:

£11,000 (£8-16,000)

Cost per vascular death avoided:

£66,000 (£42-135,000)

Overall cost-effectiveness within trial (95% CI)

Assessing subgroup effects reliably

• Analyses in different subgroups indicate:– Similar relative reduction in vascular events– Similar relative reduction in costs of vascular events– Similar absolute difference in statin treatment cost

• Hence, cost-effectiveness for subgroups estimated by applying overall treatment effects to placebo event rates and costs observed in each subgroup

Cox model on baseline characteristics used to create 5 multivariate risk groups

Risk Group

Number 5-yr risk MVE

5-yr risk MCE

5-yr risk vascular

death

1

2

3

4

5

4107

4107

4107

4107

4108

12%

18%

23%

28%

42%

4%

7%

10%

13%

22%

3%

5%

7%

10%

18%

Similar relative reduction in first MVE by prior disease and age

SIMVASTATIN PLACEBO Rate ratio & 95% CISTATIN better PLACEBO better

Baselinefeature (10269) (10267)

Prior disease

Any CHD 21.8% 27.5%

No prior CHD

CVD 18.7% 23.6%

PVD 24.7% 30.5%

Diabetes 13.8% 18.6%

Age (years)

<65 16.9% 22.1%

≥65 <70 20.9% 27.2%

≥70 23.6% 28.7%

ALL PATIENTS 19.8% 25.2%24% SE 3reduction(2P<0.00001)

0.4 0.6 0.8 1.0 1.2 1.4

Similar relative reduction in first MVE by LDL & HDL

SIMVASTATIN PLACEBO Rate ratio & 95% CI

STATIN better PLACEBO better

Baselinefeature (10269) (10267)

LDL Cholesterol (mmol/l)

<3.0 17.6% 22.2%

≥3.0 <3.5 19.0% 25.7%

≥3.5 22.0% 27.2%

HDL Cholesterol (mmol/l)

<0.9 22.6% 29.9%

≥0.9 <1.1 20.0% 25.1%

≥1.1 17.0% 20.9%

ALL PATIENTS 19.8% 25.2%24% SE 3reduction(2P<0.00001)

0.4 0.6 0.8 1.0 1.2 1.4

Similar relative reduction in first MVE by risk group

SIMVASTATIN PLACEBO Rate ratio & 95% CI

STATIN better PLACEBO better

Riskgroup (10269) (10267)

1 (low risk) 8.3% 11.8%

2 13.9% 18.2%

3 18.4% 24.9%

4 24.5% 29.6%

5 (high risk) 33.8% 41.4%

ANY OF ABOVE 19.8% 25.2%24% SE 3reduction(2P<0.00001)

0.4 0.6 0.8 1.0 1.2 1.4

Similar relative reduction in costs (£) ofall vascular events by prior disease and age

STATIN PLACEBOBaselinefeature

Prior disease

Any CHD 2158 2675

No prior CHD

CVD 1281 1641

PVD 1866 2563

Diabetes 1076 1445

23 = 0.8

Age

< 65 1572 2066

65 - 70 1958 2369

> 70 2115 2710

22 = 0.8

ALL PATIENTS 1819 2319 0.78 (0.73-0.84)

0.4 0.6 0.8 1.0 1.2 1.4

Similar relative reduction in costs (£) of all vascular events by risk group

STATIN PLACEBORiskgroup

1 (low risk) 784 1219

2 1364 1746

3 1773 2120

4 2168 2610

5 (high risk) 3000 3903

24 = 4.0

ALL PATIENTS 1819 2319 0.78 (0.73-0.84)

0.4 0.6 0.8 1.0 1.2 1.4

Similar absolute difference in statin costsby risk group

Sta

tin c

osts

(£

)

Difference £1555 £1536 £1534

£1485 £1371

(SE) (16) (17) (17) (17) (19)

S P S PS P S P S P

Risk group

1 2 3 4 5

0

500

1000

1500

2000

Similar absolute difference in statin costs by disease and age

Sta

tin c

osts

(£

)

Difference £1494 £1503 £1494 £1514 £1488

(SE) (10) (12) (11) (16) (14)

S P S PS P S P S P

Prior disease

No CHD

Any CHD

< 65 ≥ 65 < 70

≥ 70

Age (years)

0

500

1000

1500

2000

0

200

400

600

800

1000

1200

1400

1600

1 2 3 4 5

Risk Group

Cos

t offs

ets

Vascular event cost-savings by risk group

100%

50%

% C

urre

nt s

imva

stat

in p

rice

25%

12% 5-yr risk MVE

42% 5-yr risk MVE

0

200

400

600

800

1000

1200

1400

1600

1 2 3 4 5

Risk Group

Cos

t offs

ets

50%

Vascular event cost-savings by risk group

100%

% C

urre

nt s

imva

stat

in p

rice

25%

12% 5-yr risk MVE

42% 5-yr risk MVE

0

200

400

600

800

1000

1200

1400

1600

1 2 3 4 5

Risk Group

Cos

t offs

ets

50%

25%

Vascular event cost-savings by risk group

100%

% C

urre

nt s

imva

stat

in p

rice

12% 5-yr risk MVE

42% 5-yr risk MVE

Cost per MVE avoided by risk group

Overall: £11,000

12% 5-yr risk MVE

42% 5-yr risk MVE

£0

£10,000

£20,000

£30,000

£40,000

£50,000

1 2 3 4 5

Risk group

Cos

t-ef

fect

iven

ess

Cost per vascular death avoided by risk group

Overall: £66,000

12% 5-yr risk MVE

42% 5-yr risk MVE

£0

£50,000

£100,000

£150,000

£200,000

£250,000

£300,000

£350,000

£400,000

1 2 3 4 5

Risk group

Cos

t-ef

fect

iven

ess

On-going health economic analyses

• Extrapolation to effects beyond trial period

• Assessment of cost per QALY

• Adapt analyses to other countries

CONCLUSIONS: Economic evaluation of HPS

• Simvastatin allocation reduced vascular hospitalisation costs by 22% regardless of patient characteristics

• Cost-effectiveness is chiefly determined by an individual’s overall risk of vascular events (rather than by single risk factors, such as LDL)

• Statin treatment is cost-effective for a wide range of high-risk individuals (and will become increasingly so as statin prices fall)