TACTICS-TIMI 18 Economics & HRQOL Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy

Economic Data Coordination William Weintraub, MD, Steven Culler, PhD Emory UniversityElizabeth Mahoney, ScD Claudine Jurkovitz, MD, MPH Edmund Becker, PhDKaren Parker, BS Haitao Chu, MSJohn Spertus, MD, MPH TIMI Study Group Christopher Cannon, MD Brigham & Women’s HospitalCarolyn McCabe, BS Eugene Braunwald, MD Sponsor - Merck: Charles Alexander, MD Laura Demopoulos, MD John Cook, PhD Peter DiBattiste, MD John Cook, PhD Peter DiBattiste, MD Paul DeLucca, PhD Soma Nag, MS Debbie Robertson, RD MS Debbie Robertson, RD MS Economic & QoL Substudy

l Unstable angina and non-ST elevation MI: 1.3 million hospital admissions/year in the US alone l Since society cannot afford to pay for all possible medical services, and since both the costs and benefits of services vary, decisions should consider cost. l This is the first prospective evaluation of the cost of an invasive vs conservative strategy in UA/NSTEMI Study Background and Goal

TACTICS-TIMI 18 Study Design UA/ NSTEMI Early Invasive Early Conservative PCI/ CABG Cath/ PCI/ CABG Medical Rx Endpoints 6 mos Randomize - 24 hrs Chest pain hrs hrs ASA, Hep, Tirofiban Angio Hour 0 ETT +ischemia Baseline Troponin N=2220 total N=1722 US non VA

No. Pts 1 o Endpoint Death/MI Death MI Rehosp ACS P valueINV (%)CONS (%) Cardiac Events at 6 Months OR

Economic Study Hypothesis: Costs over a six month period will be similar with an invasive or conservative approach to UA/NSTEMI

Economic Methods 1 o Endpoint:Total 6 month costs (hospital, professional, meds, ER, ER, outpatient procedures, nursing home, rehab, visiting nurse, indirect) Power: Equivalence design with 80% power: the treatments will be judged equivalent if the 90% CI for the true cost difference lies within the equivalence region (-$1200, $1200) C-E Analysis :If one strategy is found to be both more costly and more effective than another, determine the incremental cost-effectiveness 2 o Endpoints:Initial hospitalization costs (hospital plus professional) 30-day costs Quality of Life

Economic Methods Cost l Hospital Costs: UB92 formulation of hospital bill (93% complete for initial hospitalization) (93% complete for initial hospitalization) l Physician Costs: Model based on share of hospital bill by DRG l Outpatient Costs: Medicare Fee Schedule l Medication Costs: Average Wholesale Price l Indirect Costs: Lost wages estimated Quality of Life l Angina: Seattle Angina Questionnaire l Utility: Health Utilities Index

Cost of Initial Hospitalization Professional Costs Hospital Costs Difference between groups = $1,994 (95% C.I. $688, $3329) $9,619 $3,372 $3,047 $11, ,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 InvasiveConservative Cost ($) $14,660 $12,667

6 Month Follow-Up Costs Indirect Other Direct Rehosp Difference -$1,140 (95% C.I. -$2165, -$50) $2,910 $3,891 $1,120 $1,125 $2,033 $2, InvasiveConservative Cost ($) $6,063 $7,203

Primary Endpoint: Total Costs 6 Months Follow-up Initial Hosp $14,553 $12,784 $6,063 $7, ,000 10,000 15,000 20,000 25,000 InvasiveConservative Cost ($) $20,616 $19,987  Events = -35/1000 patients (90% CI: -$912, $2162)  Cost = $629 (95% CI: -$1273, $2465)

 Cost = $605 (95% CI: -$2466, $3466) Effect of Troponin Status on 6 Month Primary Events & Costs $11,096 $5,410 $9,403 $6,179 InvasiveConservative Initial HospFollow-up $17,523 $6,737 $15,527 $8,128 InvasiveConservative Troponin +  Events = -99/1000 pts  Cost = $924 (95% CI: -$2043, $3654) Troponin -  Events = +24/1000 pts $24,260$23,655 $16,506 $15,582 Total Cost ($)

Effect of ST Segment Status on 6 Month Primary Events & Costs InvasiveConservative $18,139 $7,039 $11,212 $6,656 $13,234 $5,704 $16,602 $8,533 InvasiveConservative  Cost = $42 (95% CI: -4801, 4050) ST Segment +  Events = -99/1000 pts  Cost = $1070 (95% CI: -772, 2887) ST Segment -  Events = +3/1000 pts Total Cost ($) Initial HospFollow-up $25,178$25,135 $18,938$17,868

Effect of Gender on 6 Month Primary Events & Costs $14,418 $6,045 $12,226 $6,489 InvasiveConservative Initial HospFollow-up $14,634 $6,074 $13,109 $7,620 InvasiveConservative  Cost = $21 (95% CI: -2105, 2073)  Cost = $1,748 (95% CI: -2163, 4760) MaleFemale  Events = -41/1000 pts  Events = -26/1000 pts Total Cost ($) $20,708$20,729 $20,463 $18,715

$12,589 $7,444 $11,172 $8,343 InvasiveConservative $16,950 $4,377 $14,726 $5,829 Invasive Conservative Total Cost ($)  Cost = $772 (95% C.I , 3668)  Cost = $518 (95% C.I , 2596) Age > 65Age < 65  Events = -46/1000 pts  Events = -29/1000 pts Effect of Age on 6 Month Primary Events & Costs Initial HospFollow-up $21,327 $20,555 $20,033$19,515

Effect of Diabetes on 6 Month Primary Events & Costs $12,504 $7,088 InvasiveConservative $16,691 $7,514 $13,701 $5,485 $13,481 $7,492 InvasiveConservative  Cost = $3,232 (95% CI: -676, 6573) Diabetes  Events = -76/1000 pts  Cost = -$406 (95% CI: -2458, 1746) No Diabetes  Events = -22/1000 pts Total Cost ($) Initial HospFollow-up $24,205 $20,973 $19,186$19,592

Coefficient t value p value Intercept14, <.0001 Troponin  , <.0001 ST Shift 5, <.0001 Diabetes3, R 2 = Multivariate Predictors of Total Six Month Costs

p-value InvasiveConservative  Utility: Baseline 30 Day 6 Month Life Years QALYs Utility, Life Years and Quality-Adjusted Life Years (QALYs)

Utility and Cost-Utility Analysis Fewer Cardiovascular Events With Invasive Strategy However: No significant difference in Cost No significant difference in Survival No significant difference in Utility Thus: Marginal Cost/QALY with Invasive vs Conservative Strategy Cannot be Reliably Estimated

Seattle Angina Scores Physical Functioning Angina Stability Angina Frequency Treatment Satisfaction Quality of Life Invasive Conservative  6M BL

Summary l Total 6 month costs are similar in the two treatment arms  Initial hospital costs are higher with an invasive strategy  Follow-up costs are higher with a conservative strategy l ST+ & Troponin+ subgroups show greater benefit at similar six month cost benefit at similar six month cost

Conclusion In UA/NSTEMI treated with GPIIb/IIIa blockade: The benefit of the invasive strategy is achieved without an economically relevant increase in cost