Valentin Fuster. AHA 2012 Congress - American Heart Association.Find more articles on our web site.

1. Cost-Effectiveness of PCI with Drug Eluting
Stents vs. Bypass Surgery for Patients with
Diabetes and Multivessel CAD:
Results from the FREEDOM Trial
Elizabeth A. Magnuson, Valentin Fuster, Michael E. Farkouh,
Kaijun Wang, Katherine Vilain, Haiyan Li, Jaime Appelwick,
Victoria Muratov, Lynn A. Sleeper, Mouin Abdallah, David J. Cohen
Saint Luke’s Mid America Heart Institute
University of Missouri-Kansas City
Kansas City, Missouri

2. Disclosures
• FREEDOM was supported by U01 grants
#01HL071988 and #01HL092989 from the National
Heart Lung and Blood Institute
Other support
 Drug eluting stents were provided by Cordis, Johnson and
Johnson and Boston Scientific
 Abciximab and an unrestricted research grant were provided
by Eli Lilly and Company
 Clopidogrel was provided by Sanofi Aventis and Bristol-
Myers Squibb

3. Background
Time to Death/MI/Stroke
PCI/DES
30 CABG
Death/Stroke/MI, %
Logrank P=0.005
20 PCI/DES
CABG
10
5-Year Event Rates: 26.6% vs. 18.7%
0
0 1 2 3 4 5
Years post-randomization

4. Patient Flow
1900 patients randomized
947 assigned to 953 assigned to PCI
CABG
36 no
procedure 9 no procedure
(withdrawn) (withdrawn)
911 underwent 944 underwent
revascularization revascularization
893 initial 18 initial 939 initial 5 initial
CABG PCI PCI CABG
Median follow-up duration: 47 months

5. Economic Study Analysis Plan
Primary Endpoint:
• Incremental cost-effectiveness ratio expressed as
cost per quality-adjusted life year (QALY) gained
» Costs and QALYs were discounted at 3% annually
General Approach – 2 Stages:
• In-trial analysis based on observed survival, health
state utility (EQ-5D), and costs derived from reported
health care resource use during the trial period
• Lifetime analysis based on projections of survival,
quality-adjusted survival and costs beyond the trial
period

6. Costing Methods
PCI and CABG Procedures:
• Cath lab and CABG-related procedure costs based on
measured resource utilization (procedure duration,
balloons, stents, wires, etc.) and current unit costs
DES cost = $1500/stent
• Ancillary hospital costs based on regression models
developed from 2010 MedPAR data for FREEDOM-
eligible patients
 Clinical events and complications rather than LOS were used
as key predictors to avoid distortions due to marked differences
in LOS across different countries/health care systems
Additional costs: CV and non-CV rehospitalizations, MD fees,
outpatient CV care/testing and medications, cardiac rehabilitation
and nursing home stays

7. Index Procedure Resource Use*
CABG PCI
PCI procedures
1 66.6%
2 30.9%
3-4 2.3%
Drug-eluting stents 4.1 ± 1.9
Paclitaxel-eluting 45.6%
Sirolimus-eluting 51.7%
Other drug-eluting stents 2.7%
Procedure duration (mins) 248 ± 78 107 ± 6.7
Total Procedure Cost $9,739 ± $2,453 $13,014 ± $5,173
* Per protocol population (includes planned staged procedures)

8. Index Hospitalization Costs
Δ = $8,622
(p<0.001))
$34,467
$25,845
* ITT population (includes planned staged procedures)

9. 5-Year Follow-up Resource Utilization
Rates per 100 person-years
20
P<0.001
P=0.52
15
10
P<0.001 17.2
14.6
12.8
10.8
5
6.8
3.3
0 1.7
0
PCI Procedures CABG Procedures CV Hospitalizations Non-CV
Hospitalizations
CABG PCI

10. Annual and Cumulative Costs: Years 1- 5
Annual
$25,000 Cumulative
$70,000
$60,000
$20,000 Δ costs = $7878
$50,000
$15,000
Δ costs = $3641 $40,000
$30,000
$10,000
$20,000
$5,000
$10,000
$0 $0
Year 1 Year 2 Year 3 Year 4 Year 5
CABG Annual Cost PCI Annual Cost CABG Cumulative Cost PCI Cumulative Cost

11. Annual Differences in Life Years and QALYs
Time Since
Δ Life Years Δ QALYs
Randomization
(CABG-PCI) (CABG-PCI)
(Years)
1 -0.008 -0.033
2 -0.010 -0.034
3 -0.0006 -0.029
4 +0.015 -0.004
5 +0.053 +0.031

12. Markov Model
For the Projection of Post-Trial Life Years, QALYs and Costs
• Monthly risk of death based on age, sex and race-
matched data from US life tables calibrated to the
observed 5 year mortality for the PCI population
 CABG effect based on a landmark analysis for years 2-5:
mortality hazard ratio for CABG vs. PCI = 0.60
• Base case: Gradual attenuation of CABG effect
 Mortality hazard ratio increases from 0.60 to 1 in a linear
fashion between 5 and 10 years; no impact of CABG beyond
10 years
• Long-term costs and utility weights obtained from
regression models developed from trial data

13. In-Trial and Projected Survival
1 0.053 life years
CABG
0.8 PCI
0.6 1.266 total life years
Survival
gained with CABG
(0.794 when discounted at 3% annually)
0.4
0.2
0
0 5 10 15 20 25 30 35
Years post-randomization

14. Lifetime Cost-Effectiveness Results
$20,000
 Cost  Cost
 QALY  QALY
∆Long-term Cost (CABG – PCI)
$10,000
$0 Cost = $5392
∆QALY = 0.663 years
$8132/QALY gained
with CABG
-$10,000
 Cost
$50,000 per QALY  Cost
 QALY  QALY
-$20,000
-2 -1 0 1 2
∆QALYs (CABG – PCI)
Costs and QALYs discounted 3% annually

15. Cost-Effectiveness of CABG vs. PCI
Sensitivity Analysis – No CABG Effect Beyond 5 Yrs
1
No CABG Effect
Years 5 - 10
0.754 total life years
0.8 gained with CABG
(0.439 when discounted at 3% annually)
0.6
Survival
0.4 CABG
PCI
0.2
Δ Costs $9,485
Δ QALYs 0.351
0
ICER $27,022
0 5 10 15 20 25 30 35
Years post-randomization
Pr < $50K/QALY= 82.4%

16. Cost-Effectiveness of CABG vs. PCI
SYNTAX Score Tertiles
Low (<23) Mid (23-32) High (>32)
$20,000
$10,000
$0
-$10,000
-$20,000
-2 -1 0 1 2 -2 -1 0 1 2 -2 -1 0 1 2
Δ Costs $8,784 Δ Costs $4,160 Δ Costs $973
Δ QALYs 0.407 Δ QALYs 0.997 Δ QALYs 0.315
ICER $21,582 ICER $4,172 ICER $3,088
Costs and QALYs discounted 3% annually

17. Subgroups
Prob.
Subgroup Δ Costs Δ QALYs ICER
< $50,000
Male (n=1328) $3,059 0.778 $3,932 99.8
Female (n=527) $9,249 0.510 $18,135 77.3
Age <60 (n=624) $11,190 1.160 $9,647 99.8
Age 60-69 (n=621) -$1,765 0.276 Dominant 80.5
Age ≥70 (n=610) $6,892 0.349 $19,748 71.9
US (n=351) $4,701 1.120 $4,197 98.1
Non-US (n=1504) $5,622 0.576 $9,760 96.5

18. Summary (1)
• CABG is associated with initial costs ≈ $9,000/patient
higher than PCI
• Partially offset by lower costs associated with repeat
revascularization and to a lesser extent cardiac meds
• At 5 years, CABG improved quality-adjusted life
expectancy by ~ 0.03 years while increasing total
costs by ~ $3,600/patient
• Over a lifetime horizon, CABG associated with 0.66
QALYs gained and ~$5,400/patient higher costs
yielding an ICER of $8,132/QALY gained

19. Summary (2)
• Results were robust to a broad range of
sensitivity analyses regarding the duration of
the CABG effect on both survival and costs
• Results were also consistent across a wide
range of subgroups

20. Conclusions
• For patients with diabetes and multivessel
CAD, CABG provides not only better long-
term clinical outcomes than DES-PCI but
these benefits are achieved at an overall cost
that represents an attractive use of societal
health care resources
• These findings provide additional support for
existing guidelines that recommend CABG for
diabetic patients with multivessel CAD