1. Hemostatic Agents: Cost- Effectiveness Issues Peter K. Smith, MD Professor and Chief Thoracic Surgery Duke University

2. Tranexamic RCT Cardiac Surgery (n=163) 10 mg/kg (incision)  1 mg/kg/hr Horrow et al. Circulation 1991; 84:2063

3. Aprotinin vs EACA Efficacy - Demographics Bennett-Guerrero et al. Anesthesiology 1997;87:1373

4. Aprotinin vs EACA: Efficacy Bennett-Guerrero et al. Anesthesiology 1997;87:1373

5. High-Dose Aprotinin Original Administration Regimen Royston et al Lancet 1987 Dec 5;2:1289-91 200 ml LoadingDose Operation Period Bypass Period 50 ml / h Constant Infusion Constant InfusionPump-PrimeDoseTestDose 1 ml

6. Aprotinin Dosing Mossinger et al, ATS 1998;65:S45-51

7. Aprotinin Dosing Half-dose FDA Regimen B –1 ml (10,000 KIU) test dose –100 ml (1,000,000 KIU) loading dose –100 ml (1,000,000 KIU) pump prime –25 ml (250,000 KIU) per hour CPB

8. Aprotinin Dosing Mossinger et al, ATS 1998;65:S45-51

9. Aprotinin Effect on Survival

10. Aprotinin and Myocardial Infarction

11. Aprotinin and Stroke Incidence * * * *

12. Cost of Therapy Drug cost Cost of storage and administration Indirect costs Cost of complications related to the drug –In-Hospital –Lifetime

13. Cost Savings Reduction of blood products and their complications Reduced OR time and incidence of return Reduction of inflammatory syndrome Reduction of complications related to the drug Cardiac team satisfaction Patient satisfaction

14. Aprotinin vs EACA - Efficacy/Cost Bennett-Guerrero et al. Anesthesiology 1997;87:1373 Prospective randomized double-blind trial Repeat median sternotomy- CABG, valve, or both n= 204 High dose EACA or Aprotinin (on incision) Efficacy analysis Cost/benefit analysis (bleeding related costs)

15. Aprotinin vs EACA Cost/Benefit Bennett-Guerrero et al. Anesthesiology 1997;87:1373 Perspective of the hospital Bleeding related costs (not charges), e.g. drug, direct & indirect blood product costs, OR time No differences in other outcomes expected or seen Costs Aprotinin Rx higher ($1,813 vs $1,088*) Sensitivity analysis w/ half dose aprotinin- no chg Threshold value for aprotinin = $486

16. Lifetime Cost of Therapy Myocardial Infarction Lifetime Costs –~$25,000 more than matched (age, gender) patients without MI –With an incidence of 1%, 1 of 100 patients would generate $25,000 in total cost; or –$250 per patient per percent MI change Stroke Lifetime Costs –~$100,000 more than matched patients without stroke –With an incidence of 1%, 1 of 100 patients would generate $100,000 total cost; or –$1000 per patient per percent stroke change

17. Cost Effectiveness of Aprotinin Drug cost is dose dependent and linear Effects are dose dependent and non-linear Effects are only well known at the three doses tested in double-blind trials

18. Aprotinin Dose vs Hemostatic Factors Given Data from US Multicenter Studies for Repeat CABG Surgery 0 2 4 6 8 Hemostatic Factors Given (Units) 02505007501000 Total Dose of Aprotinin (mg) y = -2.940LOG(x) + 9.802

19. Aprotinin Dose vs Hemostatic Factors vs Cost Data from US Multicenter Studies for Repeat CABG Surgery 0 2 4 6 8 Hemostatic Factors Given (Units) 02505007501000 Total Dose of Aprotinin (mg) $1200 $600

20. Aprotinin Dose vs Definite MI Data from US Multicenter Studies for All CABG Surgery 0 2 4 6 8 Hemostatic Factors Given (Units) 02505007501000 Total Dose of Aprotinin (mg) 10% 5%

21. Aprotinin Dose vs Mortality Data from US Multicenter Studies for All CABG Surgery 0 2 4 6 8 Hemostatic Factors Given (Units) 02505007501000 Total Dose of Aprotinin (mg) 5% 2.5%

22. Aprotinin Dose vs Stroke Outcome Data from US Multicenter Studies for All CABG Surgery 0 2 4 6 8 Hemostatic Factors Given (Units) 02505007501000 Total Dose of Aprotinin (mg) 3% 2% 1%

23. Randomized Trial Analysis Resources used (OR time, blood tx, ICU LOS, Total LOS, etc, etc) as well as age, gender and complication rate were analyzed from the randomized patients. Model developed on Duke 1300 CABG patients with same resources related multivariably to actual cost. Adjusted model R 2 =0.74

25. Randomized Trial Composition

26. Cost Model Coefficients

27. Itemized Resources-Primary CABG

28. Complications-Primary CABG

29. Randomized Trial Resource Use Data: Primary CABG Transformed to Cost Through Duke Data Model

30. Cost-Primary CABG

31. Itemized Resources-Redo CABG

32. Complications-Redo CABG

33. Randomized Trial Resource Use Data: Redo CABG Transformed to Cost Through Duke Data Model

34. Cost-Redo CABG