Presented by Stephanie Earnshaw, MD, MPH, at UCSF's symposium "The Role of Risk Stratification and Biomarkers in Prevention of Cardiovascular Disease" in Jan 2012.

1. Base Primary Prevention Decision Model Role of Risk Stratification and Biomarkers in Prevention of Cardiovascular Disease Symposium Stephanie Earnshaw January 30, 2012

4. Methods: Model Structure CVD = cardiovascular disease; GI = gastrointestinal.

9. Methods: Model Parameters—Efficacy CI = confidence interval; RR = relative risk. a Range: 95% CI or estimate of plausible range. Parameter Base-Case Value (Range a ) Source Aspirin GIB RR (no history of GIB) 2.0 Hernandez et al. (2006) GIB RR (history of GIB) 10.0 Hernandez et al. (2006) Angina RR 1.0 (0.80, 1.20) Assumption Stroke RR (males) 1.06 (0.91, 1.24) Sanmuganathan et al. (2001) Stroke RR (females) 0.76 (0.63, 0.93) Ridker et al. (2005) MI RR (males) 0.70 (0.62, 0.79) Sanmuganathan et al. (2001) MI RR (females) 1.01 (0.84, 1.21) Ridker et al. (2005)

10. Methods: Model Parameters—Efficacy a Range: 95% CI or estimate of plausible range. Parameter Base-Case Value (Range a ) Source Statin GIB RR 1.00 Assumption Myopathy 0.001 (0.0005, 0.05) Graham et al. (2004) Angina RR 0.68 (0.49, 0.95) Downs et al. (1998) Stroke RR 0.85 (0.57, 1.28) White et al. (2000); Briel et al. (2004) MI RR 0.70 (0.68, 0.79) Pignone et al. (2000)

11. Methods: Model Parameters—Mortality a Range: 95% CI or estimate of plausible range. Parameter Base-Case Value (Range a ) Source Absolute increase in mortality due to having hemorrhagic stroke 0.37 Roger et al. (2011) Absolute increase in death due to GIB 0.00001 (0.000001, 0.0001) Expert clinical opinion Myopathy 0.00001 (0.000001, 0.000100) Graham et al. (2004) No treatment CHD Death RR 1.0 Assumption Aspirin CHD death RR (males) 0.87 (0.70, 1.09) Hayden et al. (2002) CHD death RR (females) 1.00 (0.80, 1.20) Assumption

12. Methods: Model Parameters—Mortality a Range: 95% CI or estimate of plausible range. Parameter Base-Case Value (Range a ) Source Aspirin (continued) All-cause death RR when aspirin used in secondary prevention 0.85 (0.80, 0.90) He et al. (1998) All cancers 0.78 (0.70, 0.87) Rothwell et al. (2011) Colorectal cancer 0.60 (0.45, 0.81) Statins CHD death RR (males) 0.89 (0.81, 0.98) Mills et al. (2008) CHD death RR (females) 0.89 (0.81, 0.98) Assumed to be same as males Cancer mortality 1.0 Assumption

13. Methods: Model Parameters—Mortality a Range: 95% CI or estimate of plausible range. Parameter Base-Case Value (Range a ) Source Hazard ratios After MI 3.7 (3.0, 4.7) Lampe et al. (2000) After angina 3.0 (2.1, 4.2) Lampe et al. (2000) After stroke 2.3 (1.0, 4.6) Dennis et al. (1993)

14. Methods: Model Parameters—Annual Costs HCUP = Healthcare Cost and Utilization Project Note: All costs were inflated to 2011 dollars using the Medical Consumer Price Index when appropriate Parameter Base-Case Value Source Aspirin drug costs $9.12 Walgreens.com Statin drug costs $48.55 Generic price at Target.com Healthy, on aspirin $71.01 Ingenix RBRVS (2011): assume 1 physician visit Healthy, on statins $163.43 Ingenix RBRVS (2011): assume 1 physician visit + an additional physician visit and a lipid panel GIB, acute care $16,025 2008 HCUP data set; Friedman et al. (2002) Myopathy $17,799 2008 HCUP data set; Friedman et al. (2002) GIB and myopathy, ongoing care $71.01 Assumption

15. Methods: Model Parameters—Annual Costs Note: All costs were inflated to 2011 dollars using the Medical Consumer Price Index when appropriate a Costs of ongoing care included physician visits, institutionalization, and acute care for a percentage of patients who experienced subsequent events, as appropriate Parameter Base-Case Value Source Angina, acute care $14,638 2008 HCUP data set; Friedman et al. (2002) Angina, ongoing care a $6,698 Russell et al. (1998) MI, acute care $36,129 2008 HCUP data set; Friedman et al. (2002) MI, ongoing care a $3,425 AHA (2002); Russell et al. (1998) Stroke, acute care $25,992 2008 HCUP data set; Friedman et al. (2002) Stroke, ongoing care $2,001 AHA (2002); Ingenix RBRVS (2011)

16. Methods: Model Parameters—Utilities a We assume individuals with myopathy to have a lower utility than that of a healthy individual, but higher than one with GI bleed. Thus, we assume a utility of (1-0.94)/2 = 0.97 Parameter Base –Case Value (Range a ) Source Healthy 1.0 Assumption Taking medications 1.0 (0.985, 1.0) Expert opinion GIB 0.94 (0.88, 1.00) Augustovski et al. (1998) Myopathy 0.97 (0.94, 1.00) Assumption a Post GIB and myopathy 1.000 Assumption Angina 0.929 (0.923, 1.00) Nease et al. (1995) Post angina 0.997 (0.997, 1.00) Nease et al. (1995) MI 0.87 (0.82, 0.92) Tsevat et al. (1993) Post MI 0.91 (0.86, 0.96) Tsevat et al. (1993)

17. Methods: Model Parameters—Utilities Parameter Base –Case Value (Range a ) Source Stroke 0.61 (0.48, 0.83) Augustovski et al. (1998) Post stroke 0.830 Gore et al. (1995) Death 0.0 Assumption

20. Results: 45 Year Old Men with 7.5% 10 Year CHD Risk 45 year old man with 7.5% 10 year CHD risk aspirin versus no treatment comparison: statin price at $0.133/day, time horizon=10 years, no cancer mortality benefit when using aspirin Preliminary Results

21. Clinical Events (per 1,000): 45 Year Old Men with 7.5% 10 Year CHD Risk-Aspirin vs No Treatment Preliminary Results Outcome Aspirin No Treatment MI 24.43 34.58 CHD death 8.54 9.75 Angina 35.81 35.63 Stroke 7.61 7.15 GIB 17.95 8.96 Myopathy 0 0 All deaths 83.26 84.97

22. Results: 55 Year Old Women with 7.5% 10 Year CHD Risk 55 year old woman with 7.5% 10 year CHD risk statin versus no treatment comparison: statin price at $0.133/day, time horizon=10 years, no cancer mortality benefit when using aspirin Preliminary Results

23. Clinical Events (per 1,000): 55 Year Old Women with 7.5% 10 Year CHD Risk-Statin vs No Treatment Preliminary Results Outcome Statin No Treatment MI 15.68 22.11 CHD death 5.37 5.96 Angina 27.03 39.28 Stroke 8.98 10.44 GIB 13.36 13.22 Myopathy 9.18 0 All deaths 116.64 118.72

24. Sensitivity Analysis: Time Horizon a 45 year old men, 7.5% 10 year CHD risk, aspirin vs no treatment b 55 year old women, 7.5% 10 year CHD risk, statin vs no treatment Preliminary Results Time Horizon ICER (Men a ) ICER (Women b ) 10 years -$22,570 $44,357 20 years -$13,702 $7,650 Lifetime -$5,645 $2,595

25. Sensitivity Analysis: Statin Cost 45 Year Old Men with 7.5% 10 Year CHD Risk-Aspirin vs No Treatment Patients on no treatment progress to CVD events quicker than patients on aspirin. Patient in the post CVD event health states are on optimal secondary prevention of aspirin+statins. As a result, as no treatment patients go on secondary prevention, the costs for these patients increase which causes the difference in costs between treating with aspirin and no treatment increase Preliminary Results

26. Sensitivity Analysis: Statin Cost 55 Year Old Women with 7.5% 10 Year CHD Risk-Statin vs No Treatment Preliminary Results

27. Sensitivity Analysis: Disutility for Taking a Pill 45 Year Old Men with 7.5% 10 Year CHD Risk-Aspirin vs No Treatment As the disutility associated with taking a pill increase (i.e., utility of taking a pill decreases) treating with aspirin is less effective than no treatment. Thus, the denominator of the ICER becomes smaller and the ultimate ICER becomes more negative (i.e., the difference in costs do not change) Preliminary Results

28. Sensitivity Analysis: Disutility for Taking a Pill 55 Year Old Women with 7.5% 10 Year CHD Risk-Statin vs No Treatment Preliminary Results

29. Sensitivity Analysis: 45 Year Old Men with 7.5% 10 Year CHD Risk One-way sensitivity analyses: 45-year-old man with a 10-year 7.5% coronary heart disease risk, statin cost = $0.133 and no cancer mortality benefit for aspirin: Aspirin vs no treatment Preliminary Results

30. Sensitivity Analysis: 55 Year Old Women with 7.5% 10 Year CHD Risk One-way sensitivity analyses: 55-year-old woman with a 10-year 7.5% coronary heart disease risk, statin cost = $0.133 and no cancer mortality benefit for aspirin: Statin vs no treatment Preliminary Results

31. Sensitivity Analysis: 45 Year Old Men with 7.5% 10 Year CHD Risk Probabilistic sensitivity analyses: 10,000 runs of a 45-year-old man with a 10-year 7.5% coronary heart disease risk, statin cost = $0.133 and no cancer mortality benefit for aspirin: Aspirin vs no treatment % Cost Saving: 95.3% % Cost Effective: 99.1% Preliminary Results

32. Sensitivity Analysis: 55 Year Old Women with 7.5% 10 Year CHD Risk Probabilistic sensitivity analyses: 10,000 runs of a 55-year-old woman with a 10-year 7.5% coronary heart disease risk, statin cost = $0.133 and no cancer mortality benefit for aspirin: Statin vs no treatment % Cost Saving: 5.8% % Cost Effective: 54.3% Preliminary Results