Economic Evaluation of MRC/BHF Heart Protection Study: Cost-Effectiveness Analysis

1. Economic evaluation of MRC/BHF Heart Protection Study Heart Protection Study Collaborative GroupUniversity of Oxford UK

2. 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

3. 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

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

5. 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)

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

7. 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)

8. 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

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

10. Similar relative reduction in first MVE by prior disease and age Baseline SIMVASTATIN PLACEBO Rate ratio & 95% CI (10269) (10267) feature STATIN better PLACEBO better 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% 24% SE 3 ALL PATIENTS 19.8% 25.2% reduction (2P<0.00001) 0.4 0.6 0.8 1.0 1.2 1.4

11. Similar relative reduction in first MVE by LDL & HDL Baseline SIMVASTATIN PLACEBO Rate ratio & 95% CI (10269) (10267) feature 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% 24% SE 3 ALL PATIENTS 19.8% 25.2% reduction (2P<0.00001) 0.4 0.6 0.8 1.0 1.2 1.4

12. Similar relative reduction in first MVE by risk group Risk SIMVASTATIN PLACEBO Rate ratio & 95% CI (10269) (10267) group STATIN better PLACEBO better 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% 24% SE 3 ANY OF ABOVE 19.8% 25.2% reduction (2P<0.00001) 0.4 0.6 0.8 1.0 1.2 1.4

13. Similar relative reduction in costs (£) ofall vascular events by prior disease and age Baseline STATIN PLACEBO feature Prior disease Any CHD 2158 2675 No prior CHD  2 = 0.8 CVD 1281 1641 3 PVD 1866 2563 Diabetes 1076 1445 Age < 65 1572 2066  2 = 0.8 2 65 - 70 1958 2369 > 70 2115 2710 ALL PATIENTS 1819 2319 0.78 (0.73-0.84) 0.4 0.6 0.8 1.0 1.2 1.4

14. Similar relative reduction in costs (£) of all vascular events by risk group Risk STATIN PLACEBO group 1 (low risk) 784 1219 2 1364 1746  2 = 4.0 3 1773 2120 4 4 2168 2610 5 (high risk) 3000 3903 ALL PATIENTS 1819 2319 0.78 (0.73-0.84) 0.4 0.6 0.8 1.0 1.2 1.4

15. 2000 1500 1000 500 S S S S S P P P P P 0 Similar absolute difference in statin costs by risk group Statin costs (£) 2 5 4 3 1 Risk group

16. 2000 1500 1000 500 0 S S S S S P P P P P Similar absolute difference in statin costs by disease and age Statin costs (£) Any CHD ≥ 65 < 70 ≥ 70 No CHD < 65 Age (years) Prior disease

17. Vascular event cost-savings by risk group 12% 5-yr risk MVE 42% 5-yr risk MVE 100% % Current simvastatin price 50% 25%

18. Vascular event cost-savings by risk group 12% 5-yr risk MVE 42% 5-yr risk MVE 100% % Current simvastatin price 50% 25%

19. Vascular event cost-savings by risk group 12% 5-yr risk MVE 42% 5-yr risk MVE 100% % Current simvastatin price 50% 25%

20. Cost per MVE avoided by risk group 12% 5-yr risk MVE 42% 5-yr risk MVE Overall: £11,000

21. Cost per vascular death avoided by risk group 12% 5-yr risk MVE 42% 5-yr risk MVE Overall: £66,000

22. On-going health economic analyses • Extrapolation to effects beyond trial period • Assessment of cost per QALY • Adapt analyses to other countries

23. 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)