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)
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