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 Lukes Mid America Heart Institute University of Missouri-Kansas City Kansas City, Missouri

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 BristolMyers Squibb

Background
Time to Death/MI/Stroke

Death/Stroke/MI, %

30

PCI/DES CABG Logrank P=0.005

PCI/DES CABG

20

10

5-Year Event Rates: 26.6% vs. 18.7%

0 1 2 3 4 5

Years post-randomization

Patient Flow
1900 patients randomized

947 assigned to CABG

36 no procedure (withdrawn)

953 assigned to PCI

9 no procedure (withdrawn)

911 underwent revascularization

944 underwent revascularization

893 initial CABG

18 initial PCI

939 initial PCI

5 initial CABG

Median follow-up duration: 47 months

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

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 FREEDOMeligible 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

Index Procedure Resource Use*

CABG PCI procedures 1 66.6% PCI

2
3-4 Drug-eluting stents Paclitaxel-eluting Sirolimus-eluting Other drug-eluting stents Procedure duration (mins) 248 78

30.9%
2.3% 4.1 1.9 45.6% 51.7% 2.7% 107 6.7

Total Procedure Cost

$9,739 $2,453

$13,014 $5,173

* Per protocol population (includes planned staged procedures)

Index Hospitalization Costs

= $8,622 (p<0.001)) $34,467
$25,845

* ITT population (includes planned staged procedures)

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

5
6.8 3.3 0 1.7

10.8

0 PCI Procedures

CABG Procedures CV Hospitalizations

Non-CV Hospitalizations

CABG

PCI

Annual and Cumulative Costs: Years 1- 5

$25,000 Annual $70,000 Cumulative

$20,000

costs = $7878

$60,000

$50,000
$15,000

costs = $3641

$40,000

$10,000

$30,000

$20,000 $5,000 $10,000

$0 Year 1 Year 2 Year 3 Year 4 Year 5

$0

CABG Annual Cost

PCI Annual Cost

CABG Cumulative Cost

PCI Cumulative Cost

Annual Differences in Life Years and QALYs

Time Since Randomization (Years) 1 2 3 4 5

Life Years (CABG-PCI) -0.008 -0.010 -0.0006 +0.015 +0.053

QALYs (CABG-PCI) -0.033 -0.034 -0.029 -0.004 +0.031

Markov Model
For the Projection of Post-Trial Life Years, QALYs and Costs

Monthly risk of death based on age, sex and racematched 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

In-Trial and Projected Survival

1

0.053 life years CABG PCI

0.8

Survival

0.6

1.266 total life years 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

Lifetime Cost-Effectiveness Results

$20,000
Cost QALY Cost QALY

Long-term Cost (CABG PCI)

$10,000

$0

Cost = $5392 QALY = 0.663 years

$8132/QALY gained with CABG

-$10,000

Cost QALY

$50,000 per QALY

-1 0 1

Cost QALY

-$20,000 -2
Costs and QALYs discounted 3% annually

QALYs (CABG PCI)

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 gained with CABG
(0.439 when discounted at 3% annually)

0.8

0.6 Survival

0.4

CABG PCI

0.2
Costs QALYs $9,485 0.351

0
0 5 10 15 20 25 Years post-randomization 30 35

ICER

$27,022

Pr < $50K/QALY= 82.4%

Cost-Effectiveness of CABG vs. PCI

SYNTAX Score Tertiles
Low (<23)
$20,000 $10,000

Mid (23-32)

High (>32)

$0

-$10,000

-$20,000

-2

-1

-2

-1

2 -2

-1
Costs
QALYs ICER

0
$973
0.315

Costs
QALYs ICER

$8,784
0.407 $21,582

Costs
QALYs ICER

$4,160
0.997 $4,172

$3,088

Costs and QALYs discounted 3% annually

Subgroups
Subgroup
Male (n=1328) Female (n=527) Age <60 (n=624) Age 60-69 (n=621) Age 70 (n=610) US (n=351) Non-US (n=1504)

Costs
$3,059

QALYs
0.778

ICER
$3,932

Prob. < $50,000

99.8

$9,249
$11,190 -$1,765

0.510 1.160
0.276

$18,135 $9,647
Dominant

77.3 99.8
80.5

$6,892
$4,701 $5,622

0.349
1.120 0.576

$19,748
$4,197 $9,760

71.9
98.1 96.5

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

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

Conclusions
For patients with diabetes and multivessel CAD, CABG provides not only better longterm 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