This is the text extract for Statins Cost Utility Analysis, browse documents here.

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Updated cost utility analysis for statins

Scott Metcalfe Pharmac 30 January 2001 Pharmac estimates the cost-utility of providing statins to everyone with dyslipidaemia and > 10% 5-year absolute risk of cardiovascular events, at a proposed price of $0.45/day, is $1,630/QALY if statins are used over patients’ remaining lifetimes, or $1,445/QALY if statins are used for 5 years and then use is reassessed. In particular, those with established coronary heart disease (CHD) and total cholesterol > 5.5 mmol/l are estimated to have remaining lifetime and 5 -year cost/QALYs of $1,285/QALY and $1,155 respectively. Others with a >10% 5-year absolute cardiovascular risk and total cholesterol > 5.5 mmol/l have $2,110 and $1,860 cost/QALYs for the same analyses. Only one group has cost/QALYs greater than $5,000 - those with <10% 5-year absolute risk (giving less value with much higher cost/QALYs at >$13-15,000/QALY):

Cost/QALYS for statins Rx, lifetime use at 10% discount rate

discount rate: population group group 10.0% Undiscounted Discounted 5-year costs, QALYs per patient values 5-year absolute potential no. undiscounted discounted Rx costs net other % offsets cost/QALYs CHD risk pts QALYs QALYs Vote:Health costs $0.60

current price simvastatin

Average daily cost/patient (ADC)

$0.60

$0.60

$0.60

$0.45 future contracted price simv $164 $575 $688 $1,389 $3,482 $352 $1,329 $1,795 $2,645 $13,654 $1,285 $2,111 $1,631

Average cost/patient/year (AYC) past CHD >=7.5 past CHD 6.5-7.4 past CHD 5.5-6.4 past CHD <5.5 genetic LDs at risk >=20% at risk 15-19% at risk 10-14% low risk <10% past CHD others >10% risk total 61.6% 43.9% 31.7% 23.8% 35.3% 22.5% 17.5% 12.5% 3.6% 32.6% 10.3% 21.3% 16,388 39,281 66,949 54,690 2,936 25,369 46,187 107,860 1,319,776 177,308 182,352 359,660 3.73 3.49 2.53 1.34 5.13 1.92 1.80 1.64 1.05 2.49 1.77 2.13 1.09 0.93 0.54 0.26 0.66 0.54 0.45 0.36 0.10 0.59 0.41 0.50

$219 $1,362 $1,450 $1,501 $1,502 $1,843 $1,472 $1,562 $1,683 $2,034 $1,477 $1,626 $1,552

$219 -$397 -$447 -$383 -$236 -$1,149 -$387 -$362 -$311 -$168 -$353 -$348 -$350

$219 29% 31% 25% 16% 62% 26% 23% 18% 8% 24% 21% 23%

$219 $888 $1,076 $2,090 $4,950 $1,047 $2,010 $2,661 $3,815 $18,768 $1,913 $3,096 $2,409

Note that the above estimates for using statins over patients’ remaining lifetimes are based on undiscounted QALY gains (for everyone with dyslipidaemia and >10% risk) of 2.1 extra qualityadjusted life years (falling to 0.5 years after discounting at 10%), and discounted savings elsewhere in the Health Sector offsetting statin costs by 23%.

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Cost/QALYS for statins Rx, 5-year use at 10% discount rate

discount rate: population group group 10.0% Undiscounted Discounted 5-year costs, QALYs per patient values 5-year absolute potential no. undiscounted discounted Rx costs net other % offsets cost/QALYs CHD risk pts QALYs QALYs Vote:Health costs $0.60

current price simvastatin

Average daily cost/patient (ADC)

$0.60

$0.60

$0.60

$0.45 future contracted price simv $164 $520 $612 $1,257 $3,294 $326 $1,171 $1,595 $2,378 $15,343 $1,155 $1,861 $1,446

Average cost/patient/year (AYC) past CHD >=7.5 past CHD 6.5-7.4 past CHD 5.5-6.4 past CHD <5.5 genetic LDs at risk >=20% at risk 15-19% at risk 10-14% low risk <10% past CHD others >10% risk total 61.6% 43.9% 31.7% 23.8% 35.3% 22.5% 17.5% 12.5% 3.6% 32.6% 10.3% 21.3% 16,388 39,281 66,949 54,690 2,936 25,369 46,187 107,860 1,319,776 177,308 182,352 359,660 1.49 1.28 0.78 0.39 1.52 0.75 0.63 0.52 0.14 0.83 0.60 0.71 0.63 0.51 0.28 0.13 0.41 0.30 0.24 0.18 0.04 0.32 0.22 0.27

$219 $758 $770 $773 $773 $800 $771 $783 $797 $825 $771 $790 $781

$219 -$243 -$263 -$228 -$141 -$467 -$223 -$202 -$166 -$72 -$210 -$188 -$199

$219 32% 34% 29% 18% 58% 29% 26% 21% 9% 27% 24% 25%

$219 $823 $986 $1,948 $4,746 $817 $1,806 $2,405 $3,475 $21,129 $1,760 $2,769 $2,176

Note that the above estimates for using statins over 5 years are based on undiscounted QALY gains for everyone with dyslipidaemia and >10% risk of 0.7 extra quality-adjusted life years (lower than occurs with lifetime statin use), falling to 0.27 years after discounting at 10%, and discounted savings elsewhere in the Health Sector offsetting statin costs by 25% (similar to offsets with lifetime statin use). Pharmac’s analysis is based on clinical trial data on the effectiveness of statin treatment (i.e. treated versus untreated patients), applied to models of natural history of cardiovascular disease (deaths rates, rates of non-fatal events, and calculations of life expectancy), quality of life scores for each health state, and costs of treating with pharmaceuticals and to other parts of the health sector of treating or not treating with statins. The updated model involves a number of cohorts based on age, gender, 5-year absolute CHD risk, and total cholesterol levels. These groups relate to those defined in the updated guidelines published by New Zealand’s National Heart Foundation (NHF) in 19961 , i.e.: • clinically proven ischaemic heart disease (NHF risk group A1:1) • post coronary artery bypass graft (CABG) or angioplasty (A1:2) • post heart transplant • proven ischaemic stroke or unequivocal history of transient ischaemic attack due to arteriosclerosis (A1:3) • unequivocal history of intermittent claudication (A1:4) • genetic lipid disorders (familial hypercholesterolaemia, familial defective Apo B, familial combined dyslipidaemia, combined dyslipidaemia (type III)) (A2) • insulin and non-insulin dependent diabetes with established nephropathy (albumin excretion greater than 300 mg/day) total cholesterol (A3) • > 20% 5-year cardiovascular disease risk (B) • 15-20% 5-year cardiovascular disease risk (C)

1

NHF Guidelines for the assessment and management of dyslipidaemia. NZ Med J 1996;109:224-32.

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10-15% 5-year cardiovascular disease risk (D) < 10% 5-year cardiovascular disease risk (E)

Pharmac has done similar analysis previously, and the methods and results have been described in some detail (see Pharmac documents #26723 and #26220 of June 1997, available on Pharmac’s website at http://www.pharmac.govt.nz/download/statin97methods.pdf and http://www.pharmac.govt.nz/download/statin97results.pdf or freephone 0800 66 00 50). The current analysis differs from those of May 1997 and subsequently by the following features: • • Use of both 5-year and remaining lifetime timespans (previously had used 5-year horizon only). Inclusion of cerebrovascular (stroke) and peripheral vascular disease (PVD) outcomes (previously only CHD deaths and non-fatal events). Stroke and PVD event rates (a) for each cohort are derived from 4S2 placebo event rates (b), 4S placebo CHD events (b) and the cohort’s baseline CHD event rate (d), where a = b ×d÷c. Patients with stroke are assigned a quality of life score of 0.72 (from NZBD3 disability weight of 0.285, a caseweighted average including no sequelae of Netherlands BD weights4 ). Updated absolute risk estimates for genetic lipid disorders (familial hyperlipidaemia etc) - see Pharmac document #31473 of November 1997, available on Pharmac’s website at http://www.pharmac.govt.nz/download/statin97A2FH.pdf . Updated relative risk reductions, now constant across all categories of age, gender and baseline cardiovascular risk (La Rosa 19995 , HTA meta-analysis 19996, preliminary results from the MRC/BHF Heart Protection Study (HPS)7 ) at 42% for fatal (CHD death), 30% for non-fatal major CHD events, 37% for coronary surgery or angioplasty, 11% for non-MI acute CHD, 36% for both fatal and non-fatal stroke, and 27% for peripheral vascular disease events, from the 4S trial (had previously varied according to age, gender, and baseline cardiovascular risk). Note that stratification according to baseline total cholesterol levels still occurs for those with established CHD as previously, particularly affecting those with TC < 5.5 mmol/l (consistent with 4S8 , CARE9 and LIPID10 relative risk reduction patterns).

•

•

2

Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian simvastatin survival study (4S). Lancet 1994;344:1383-9. 3 Tobias M. The Burden of Disease and Injury in New Zealand. Public Health Intelligence Occasional Bulletin No. 1. Wellington: Ministry of Health, 2001. 4 Stouthard MEA, Essink-Bot M, Bonsel GJ, Barendregt PGN, et al. Disability weights for diseases in the Netherlands. Rotterdam: Department of Public Health, Erasmus University, 1997. 5 LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA. 1999;282:2340-6. 6 Ebrahim S, Smith GD, McCabe C, Payne N, Pickin M, Sheldon TA, Lampe F, Sampson F, Ward S, Wannamethee G. What role for statins? A review and economic model. Health Technol Assess. 1999;3:i-iv, 1-91. 7 http://www.ctsu.ox.ac.uk/projects/hps.shtml 8 Scandinavian Simvastatin Survival Study Group. Baseline serum cholesterol and treatment effect in the Scandinavian Simvastatin Survival study (4S). Lancet 1995;345:1274-5. 9 Sacks FM, Pfeffer MA, Moye LA, Roubleau JL, Rutherford JD, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-9. 10 The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in ptients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349-57.

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Use of 10-year age bands for cohorts aged 35-44 to 75-84 (previously 5-year age bands 35-30 to 80-84). Updated non-pharmaceutical Health Sector costs (HFA DRG prices 99/00), and updated clinical trial data (unpublished) on the effectiveness of statins at reducing such costs over time (previously had used attributable risk estimates to help derive costs offsets):

Myocardial Bypass drg Infarction drg 106,107 121-123 MI Cerebrovasc Cerebrovasc Revascula Others total ular drg 14 ular drg 15 risation drg131/13 2 CABG PTCA angina arrhythmias CVA TIA vascular other - not categorised by MSD proc $3,729 $12,093 $3,456 $1,614 $2,779 $14,581 $1,967 $5,939 $2,044 Revascularis Angina drg Arrhythmias ation drg 112 124, 125, 140 drg 138

Health sector costs/patient (differences between simvastatin and placebo groups costed on basis of NZ DRG costings)

unit cost placebo Year 1 Year 2 Year 3 Year 4 Year 5 Year 5.4 Total 5 years simvastatin Year 1 Year 2 Year 3 Year 4 Year 5 Year 5.4 Total 5 years

$238 $201 $208 $164 $176 $69 $1,057 $979

$256 $354 $397 $462 $305 $92 $1,866 $1,728

$12 $16 $20 $22 $17 $17 $104 $96

$62 $57 $73 $62 $52 $22 $329 $305

$16 $20 $19 $18 $24 $8 $104 $96

$72 $85 $125 $105 $98 $39 $525 $486

$3 $3 $2 $9 $4 $5 $25 $23

$8 $13 $3 $8 $8 $3 $43 $40

$19 $25 $25 $29 $29 $17 $143 $132

$687 $774 $871 $878 $712 $272 $4,194 $3,884

$170 $128 $101 $101 $112 $50 $662 $613

$245 $261 $267 $152 $169 $76 $1,171 $1,084

$19 $14 $20 $19 $19 $8 $98 $91

$74 $47 $42 $39 $36 $15 $254 $235

$23 $19 $33 $33 $35 $29 $170 $158

$66 $92 $85 $53 $66 $33 $394 $365

$2 $4 $4 $4 $4 $1 $18 $16

$11 $8 $5 $5 $11 $8 $48 $45

$10 $15 $20 $23 $16 $16 $99 $92

$618 $587 $577 $428 $468 $235 $2,913 $2,697

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Use only of potential (ideal) cost/QALYs based on intention-to-treat results from clinical trials (with relatively high patient continuation/adherence rates in a select population) (previously had used both potential and actual cost/QALYs, where actual cost/QALYs adjusted for likely continuation/adherence rates expected for all New Zealand users). 10% discount rate (PHARMAC’s current rate for economic analyses) (previously 11.4%).

•

Although total cholesterol levels rather than the more predictive total:HDL ratios are used to define the cohorts used in the model, differences are likely to be minor. For patients without established CHD (i.e. primary prevention - NHF risk groups A2 and B-E above), the model assumes dyslipidaemia i.e. total cholesterol > 5.5 mmol/l. The updated model has not formally included ·coronary artery bypass graft (CABG) and angioplasty patients, heart transplant patients, patients with proven ischaemic stroke or unequivocal history of transient ischaemic attack due to arteriosclerosis, patients with unequivocal history of intermittent claudication, or diabetes with established nephropathy (NHF groups A1:2, A1:3, A1:4 and A3). Results for these groups however are expected to be at least as beneficial and cost-effective as occur for those with > 20% 5-year cardiovascular disease risk (NHF group B). The modelling creates a series of quality-adjusted survival curves, showing the effects of statins on quality-adjusted life expectancy of untreated patients at various levels of risk. QALY gains are seen by the gap between untreated and treated cohorts, e.g.:

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Statin quality-adjusted survival curves

100% 90%

past CHD, treated past CHD, untreated others, untreated

% surviving, adjusting for quality of life

80%

others, treated

70%

QALYS, statins for non-CHD pts (primary prevention)

60%

50%

increase in quality-adjusted life expectancy (dQALE), primary prevention

40%

QALYS, statins for past CHD (secondary prevention)

30%

20%

increase in quality-adjusted life expectancy (dQALE), secondary prevention

10%

0% 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 F75-84 year 60 0 2 4 6 8

Before discounting, QALY gains increase with cardiovascular risk but are also highest for younger age groups:

(Undiscounted) QALYs saved by statin use over remaining lifetime, by preventing cardiovascular events (both premature deaths and ongoing morbidity)

8.0

7.0 extra years gained, quality-adjusted (QALY gains)

6.0

past CHD, >=7.5 past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5 at risk, >=20% genetic LDs, >=20% at risk, 15-19% at risk, 10-14% low risk, <10% past CHD (excpt pCHD)

5.0

4.0

3.0

2.0

1.0

0.0 M35-44 M45-54 M55-64 M65-74 M75-84 F35-44 F45-54 F55-64 F65-74 starting age/sex-group

However, discounting blunts much of these age gradients, especially for those with established CHD (who have maximum QALY gains for men aged 55-74):

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Discounted QALYs saved by statin use over remaining lifetime, by preventing cardiovascular events (both premature deaths and ongoing morbidity), 10% rate

1.4

extra years gained, quality-adjusted (QALY gains)

1.2

past CHD, >=7.5 past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5 at risk, >=20% genetic LDs, >=20% at risk, 15-19% at risk, 10-14% low risk, <10% past CHD (excpt pCHD)

1.0

0.8

0.6

0.4

0.2

0.0 M35-44 M45-54 M55-64 M65-74 M75-84 F35-44 F45-54 F55-64 F65-74 F75-84 starting age/sex-group

QALYs saved by 5 years’ statin use are somewhat less than for the above remaining lifetime use:

Discounted QALYs saved by statin use over 5 years, by preventing cardiovascular events (both premature deaths and ongoing morbidity), 10% rate

1.4

past CHD, >=7.5 past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5 at risk, >=20% genetic LDs, >=20% at risk, 15-19% at risk, 10-14% low risk, <10% past CHD (excpt pCHD)

extra years gained, quality-adjusted (QALY gains)

1.2

1.0

0.8

0.6

0.4

0.2

0.0 M35-44 M45-54 M55-64 M65-74 M75-84 F35-44 F45-54 F55-64 F65-74 F75-84 starting age/sex-group

Likewise, the model shows patterns of pharmaceutical and non-pharmaceutical costs of treating or not treating various groups with statins. Patients with established CHD have lower non-statin Health Sector costs when treated with statins than those who are not treated. However, this pattern is reversed by the cost of statins causing total costs to be higher for treated groups:

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Statin analysis cost curves: Rx costs and other costs to Vote:Health of statin vs non-statin treatment over a patient's remaining lifetime, pre-existing CHD, statin price at $0.60/day

$800

life expectancy, untreated life expectancy, treated

$700

Rx costs, treated

$600

other Vote:Health costs, untreated other Vote:Health costs, treated

annual patient cost

$500

total costs (Rx + other Vote:Health), treated

$400

$300

$200

$100

$0 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 year 59 1 3 5 7 9

Note that the above and all following graphs relate to statins priced at $0.60 weighted average daily cost. Non-statin Health Sector costs are lower and occur later for patients without established CHD, but patterns are otherwise similar to CHD for treated and untreated patients:

Statin analysis cost curves: Rx costs and other costs to Vote:Health of statin vs non-statin treatment over a patient's remaining lifetime, pre-existing CHD, statin price at $0.60/day

$600 past CHD others $500 Rx costs $400 annual patient cost other Vote:Health costs, untreated

other Vote:Health costs, treated with statins

$300

$200

$100

$0

1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60 1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59

year

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Statin analysis cost curves: total costs to Vote:Health of statin vs non-statin treatment over a patient's remaining lifetime, statin price at $0.60/day

$800

$700

past CHD, untreated, other Vote:Health costs

$600

difference between treated and untreated total costs, past CHD

others, untreated, other Vote:Health costs past CHD, treated, total costs (Rx + other Vote:Health) others, treated, total costs (Rx + other Vote:Health)

annual patient cost

$500

$400

$300

$200

$100

difference between treated and untreated total costs, others

$0 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 57 year 59 59 1 3 5 7 9

Savings from statin use occur early on, as non-statin Health Sector costs decrease alongside reduced cardiovascular events. This pattern reverses in later years as treated patients incur higher costs when surviving for longer:

Statin analysis cost curves: offsets and net costs of statin vs non-statin treatment over a patient's remaining lifetime, statin price at $0.60/day

$250

$200 difference between total treated costs and total untreated costs (statin costs + other Vote:Health costs)

$150

$100 annual patient cost

$50

$0 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 1 3 5 7 9

-$50

past CHD, net other Vote:Health costs (treated minus untreated)

-$100

others, net other Vote:Health costs (treated minus untreated) past CHD, net total costs (treated (Rx + other Vote :Health) minus untreated)

-$150 difference between treated and untreated non-statin Vote:Health costs (-ve values = savings) -$200 year

others, net total costs (treated (Rx + other Vote :Health) minus untreated)

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120%

Discounted other Vote:Health cost offsets from statins use over remaining lifetime, statin price at $0.60/day (discounted at 10%) past CHD, >=7.5

where offsets = (discounted lifetime net HS costs)/(discounted lifetime Rx statin costs) past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5

100%

at risk, >=20% genetic LDs, >=20% at risk, 15-19% at risk, 10-14% low risk, <10% past CHD (excpt pCHD)

80%

% offsets

60%

40%

20%

0% M35-44 M45-54 M55-64 M65-74 M75-84 age/sex-group F35-44 F45-54 F55-64 F65-74 F75-84

Patterns of net costs differ for 5-year statin use when compared with the above remaining lifetime use:

Discounted other Vote:Health cost offsets from statins use over 5 years, statin price at $0.60/day (discounted at 10%)

140%

where offsets = (discounted lifetime net HS costs)/(discounted lifetime Rx statin costs) past CHD, >=7.5 past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5 at risk, >=20% genetic LDs, >=20% at risk, 15-19%

120%

100%

at risk, 10-14% low risk, <10% past CHD (excpt pCHD)

% offsets

80%

60%

40%

20%

0% M35-44 M45-54 M55-64 M65-74 M75-84 age/sex-group F35-44 F45-54 F55-64 F65-74 F75-84

QALY gain and net cost patterns combine to form cost/QALY patterns. Cost/QALYs largely relate to overall cardiovascular risk. Best value-for-money (lowest cost/QALYS) occurs with those groups with highest absolute cardiovascular risk, i.e. patients with established CHD and total cholesterol >= 7.5 mmol/l. Value decreases (cost/QALYS increase) as absolute risk

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decreases. For most risk groups, especially very high risk, value is greatest at younger age groups. However, for low risk patients (<10% 5-year risk) value is lowest at younger ages:

Discounted cost/QALYS from statin use over remaining lifetime, statin price at $0.60/day (discounted at 10%)

$7,000

past CHD, >=7.5 past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5

$6,000

at risk, >=20% genetic LDs, >=20% at risk, 15-19%

$5,000

at risk, 10-14% past CHD

$/QALY

$4,000

$3,000

$2,000

$1,000

$0 M35-44 M45-54 M55-64 M65-74 M75-84 age/sex-group F35-44 F45-54 F55-64 F65-74 F75-84

Discounted cost/QALYS from statin use over remaining lifetime, statin price at $0.60/day (discounted at 10%)

$40,000

past CHD, >=7.5 past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5 at risk, >=20% genetic LDs, >=20% at risk, 15-19% at risk, 10-14% low risk, <10% past CHD (excpt pCHD)

$35,000

$30,000

$25,000 $/QALY

$20,000

$15,000

$10,000

$5,000

$0 M35-44 M45-54 M55-64 M65-74 M75-84 age/sex-group F35-44 F45-54 F55-64 F65-74 F75-84

Patterns again differ for 5-year statin use when compared with the above remaining lifetime use:

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Discounted cost/QALYS from statin use over 5 years, statin price at $0.60/day (discounted at 10%)

$7,000

past CHD, >=7.5 past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5

$6,000

at risk, >=20% genetic LDs, >=20% at risk, 15-19%

$5,000

at risk, 10-14% past CHD

$4,000 $/QALY $3,000 $2,000 $1,000 $0 M35-44 M45-54 M55-64 M65-74 M75-84 age/sex-group F35-44 F45-54 F55-64 F65-74 F75-84

Discounted cost/QALYS from statin use over 5 years, statin price at $0.60/day (discounted at 10%)

$40,000

past CHD, >=7.5 past CHD, 6.5-7.4 past CHD, 5.5-6.4 past CHD, <5.5 at risk, >=20% genetic LDs, >=20% at risk, 15-19% at risk, 10-14% low risk, <10% past CHD (excpt pCHD)

$35,000

$30,000

$25,000 $/QALY

$20,000

$15,000

$10,000

$5,000

$0 M35-44 M45-54 M55-64 M65-74 M75-84 age/sex-group F35-44 F45-54 F55-64 F65-74 F75-84

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