Transcript MRC/BHF Heart Protection Study

Economic evaluation of
MRC/BHF Heart Protection Study
Heart Protection Study Collaborative Group
University 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; or
Diabetes 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)
Vascular
death
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)
Overall cost-effectiveness within trial (95% CI)
Cost per MVE avoided:
£11,000 (£8-16,000)
Cost per vascular death avoided:
£66,000 (£42-135,000)
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
1
2
3
4
5
4107
4107
4107
4107
4108
12%
18%
23%
28%
42%
4%
7%
10%
13%
22%
5-yr risk
vascular
death
3%
5%
7%
10%
18%
Similar relative reduction in first MVE
by prior disease and age
Baseline
feature
SIMVASTATIN
(10269)
PLACEBO
(10267)
21.8%
27.5%
CVD
18.7%
23.6%
PVD
24.7%
30.5%
Diabetes
13.8%
18.6%
<65
16.9%
22.1%
≥65 <70
20.9%
27.2%
≥70
23.6%
28.7%
19.8%
25.2%
Rate ratio & 95% CI
STATIN better PLACEBO better
Prior disease
Any CHD
No prior CHD
Age (years)
ALL PATIENTS
24% SE 3
reduction
(2P<0.00001)
0.4
0.6
0.8
1.0
1.2
1.4
Similar relative reduction in first MVE
by LDL & HDL
Baseline
feature
SIMVASTATIN
(10269)
PLACEBO
(10267)
Rate ratio & 95% CI
STATIN better PLACEBO better
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%
19.8%
25.2%
ALL PATIENTS
24% SE 3
reduction
(2P<0.00001)
0.4
0.6
0.8
1.0
1.2
1.4
Similar relative reduction in first MVE
by risk group
Risk
group
SIMVASTATIN
(10269)
PLACEBO
(10267)
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%
19.8%
25.2%
1 (low risk)
ANY OF ABOVE
Rate ratio & 95% CI
STATIN better PLACEBO better
24% SE 3
reduction
(2P<0.00001)
0.4
0.6
0.8
1.0
1.2
1.4
Similar relative reduction in costs (£) of
all vascular events by prior disease and age
Baseline
feature
STATIN PLACEBO
Prior disease
Any CHD
2158
2675
CVD
1281
1641
PVD
1866
2563
Diabetes
1076
1445
< 65
1572
2066
65 - 70
1958
2369
> 70
2115
2710
1819
2319
No prior CHD
23 = 0.8
Age
ALL PATIENTS
 22 = 0.8
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
Risk
group
1 (low risk)
STATIN PLACEBO
784
1219
2
1364
1746
3
1773
2120
4
2168
2610
5 (high risk)
3000
3903
ALL PATIENTS
1819
2319
 24 = 4.0
0.78 (0.73-0.84)
0.4
0.6
0.8
1.0
1.2
1.4
Similar absolute difference in statin costs
by risk group
Difference
(SE)
£1555
(16)
£1536
(17)
S P
1
S P
2
£1534
(17)
£1485
(17)
£1371
(19)
Statin costs (£)
2000
1500
1000
500
0
S P
3
Risk group
S P
4
S P
5
Similar absolute difference in statin costs
by disease and age
Difference
(SE)
£1494
(10)
£1503
(12)
£1494
(11)
£1514
(16)
£1488
(14)
S P
No
CHD
S P
S P
≥ 65
< 70
S P
≥ 70
Statin costs (£)
2000
1500
1000
500
0
S P
Any
CHD
Prior disease
< 65
Age (years)
1600
100%
1400
Cost offsets
1200
1000
800
50%
600
400
25%
200
0
1
12%
5-yr risk MVE
2
3
Risk Group
4
5
42%
5-yr risk MVE
% Current simvastatin price
Vascular event cost-savings by risk group
1600
100%
1400
Cost offsets
1200
1000
800
50%
600
400
25%
200
0
1
12%
5-yr risk MVE
2
3
Risk Group
4
5
42%
5-yr risk MVE
% Current simvastatin price
Vascular event cost-savings by risk group
1600
100%
1400
Cost offsets
1200
1000
800
50%
600
400
25%
200
0
1
12%
5-yr risk MVE
2
3
Risk Group
4
5
42%
5-yr risk MVE
% Current simvastatin price
Vascular event cost-savings by risk group
Cost per MVE avoided by risk group
Cost-effectiveness
£50,000
£40,000
£30,000
£20,000
Overall: £11,000
£10,000
£0
1
12%
5-yr risk MVE
2
3
Risk group
4
5
42%
5-yr risk MVE
Cost per vascular death avoided by risk group
£400,000
Cost-effectiveness
£350,000
£300,000
£250,000
£200,000
£150,000
£100,000
Overall: £66,000
£50,000
£0
1
12%
5-yr risk MVE
2
3
Risk group
4
5
42%
5-yr risk MVE
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)