1. Economic evaluation of MRC/BHF Heart Protection Study Heart Protection Study Collaborative Group University 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 Simvastatin allocated Placebo allocated Avoided per 1000 (SE) All MVE27035989 (10) Vascular death 76 9115 (4)

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 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)

7. 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)

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 Risk Group Number5-yr risk MVE 5-yr risk MCE 5-yr risk vascular death 1234512345 4107 4108 12% 18% 23% 28% 42% 4% 7% 10% 13% 22% 3% 5% 7% 10% 18%

10. Similar relative reduction in first MVE by prior disease and age SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) Prior disease Any CHD21.8%27.5% No prior CHD CVD18.7%23.6% PVD24.7%30.5% Diabetes13.8%18.6% Age (years) <6516.9%22.1% ≥65 <7020.9%27.2% ≥7023.6%28.7% ALL PATIENTS19.8%25.2% 24% SE 3 reduction (2P<0.00001) 0.40.60.81.01.21.4

11. Similar relative reduction in first MVE by LDL & HDL SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Baseline feature (10269)(10267) LDL Cholesterol (mmol/l) <3.017.6%22.2% ≥3.0 <3.519.0%25.7% ≥3.522.0%27.2% HDL Cholesterol (mmol/l) <0.922.6%29.9% ≥0.9 <1.120.0%25.1% ≥1.117.0%20.9% ALL PATIENTS19.8%25.2% 24% SE 3 reduction (2P<0.00001) 0.40.60.81.01.21.4

12. Similar relative reduction in first MVE by risk group SIMVASTATINPLACEBORate ratio & 95% CI STATIN betterPLACEBO better Risk group (10269)(10267) 1 (low risk)8.3%11.8% 213.9%18.2% 318.4%24.9% 424.5%29.6% 5 (high risk)33.8%41.4% ANY OF ABOVE19.8%25.2% 24% SE 3 reduction (2P<0.00001) 0.40.60.81.01.21.4

13. Similar relative reduction in costs (£) of all vascular events by prior disease and age STATINPLACEBOBaseline feature Prior disease Any CHD21582675 No prior CHD CVD12811641 PVD18662563 Diabetes10761445  2 3 =0.8 Age < 6515722066 65 - 7019582369 > 7021152710  2 2 =0.8 ALL PATIENTS181923190.78 (0.73-0.84) 0.40.60.81.01.21.4

14. Similar relative reduction in costs (£) of all vascular events by risk group STATINPLACEBORisk group 1 (low risk)7841219 213641746 317732120 421682610 5 (high risk)30003903  2 4 =4.0 ALL PATIENTS181923190.78 (0.73-0.84) 0.40.60.81.01.21.4

15. Similar absolute difference in statin costs by risk group Statin costs (£) Difference£1555£1536£1534£1485£1371 (SE)(16)(17) (19) S P S P S P S P S P Risk group 1 2 3 4 5 0 500 1000 1500 2000

16. Similar absolute difference in statin costs by disease and age Statin costs (£) Difference£1494£1503£1494£1514£1488 (SE)(10)(12)(11)(16)(14) S P S P S P S P S P Prior disease No CHD Any CHD < 65 ≥ 65 < 70 ≥ 70 Age (years) 0 500 1000 1500 2000

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

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

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

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

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

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)