US cost-effectiveness of simvastatin in 20,536 people at different levels of vascular disease risk: randomised placebo-controlled trial UK Medical Research Council ($14M); British Heart Foundation ($2M); Merck ($8M); Roche Vitamins ($8M) Designed, conducted & analysed independently of all sources of support

HPS: Eligibility criteria Increased risk of CHD death due to prior disease –Myocardial infarction or other CHD –Occlusive disease of non-coronary arteries –Diabetes mellitus or treated hypertension UK adults aged years Total cholesterol  135mg/dl (  3.5 mmol/l) Statin or vitamins not considered clearly indicated or contraindicated by patient’s own doctors

Two questions addressed for people at different vascular disease risk What is the US cost-effectiveness of allocation to simvastatin 40mg daily over the 5-year timescale of the trial? What is the US cost-effectiveness of simvastatin 40mg daily continued for life?

Vascular disease risk subgroups in HPS Risk Group Number of patients 5-yr risk MVE 5-yr risk MCE 5-yr risk vascular death % 18% 23% 28% 42% 4% 7% 10% 13% 22% 3% 5% 7% 10% 18% Cox model on baseline characteristics used to create five similar sizes multivariate risk groups

Economic analyses using US costs Study simvastatin (40mg at $3.83 daily) & any non-study statin (2003 Wholesale Acquisition Costs) Hospitalisations for vascular events mapped into CMS DRGs; 2003 average Medicare payments Costs and outcomes discounted at 3% per annum

Within trial cost-effectiveness in vascular disease risk subgroups Analyses in different subgroups indicate: –Similar relative reductions in major vascular events (MVEs) of ~ 25% –Similar relative reductions in costs of vascular event hospitalisations of ~19% –Similar additional statin treatment costs of ~ $5,500 Hence, US cost effectiveness of statin per MVE and per vascular death avoided was estimated for subgroups by applying overall treatment effects to placebo event rates and costs observed in each subgroup

Within trial cost per MVE avoided by risk group

Within trial cost per VASCULAR DEATH avoided by risk group

Methods for lifetime extrapolation model Predicts future non-fatal vascular events, vascular deaths and vascular hospitalisation costs from HPS within trial data Uses US life-table to predict non-vascular deaths Adjusts survival for US age and sex specific quality of life Estimated outcomes: Life year gained (LY) Cost per quality adjusted life year gained (QALY)

Within trial validation of the model for major vascular events

Lifetime statin treatment: Life years gained as estimated from the model Age at initiation of statin ≥70 12% % % % % year major vascular event risk

Lifetime treatment: Cost per Quality Adjusted Life Year gained

Lifetime treatment: Cost per QALY beyond the HPS population

CONCLUSIONS: US cost-effectiveness of simvastatin 40mg daily At current US prices, statin cost-effectiveness is chiefly determined by an individual’s overall risk of vascular events (rather than age or single risk factors, such as LDL) In the US, statin treatment is cost-effective (i.e. less than $50,000 per QALY) for a wide range of individuals at major vascular event risk as low as 2-3% per annum At lower prices of generic statins cost-effectiveness of statins would improve

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