0. Cost-Effectiveness of Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients with Stable Coronary Disease: Results from the FAME 2 trial
William Fearon, Bernard De Bruyne, Nico Pijls, David Shilane, Derek Boothroyd, Pim Tonino, Emmanuele Barbato, Peter Juni, and Mark Hlatky on behalf of the FAME 2 Trial Investigators

1. Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Grant/Research Support
Consulting Fees/Honoraria
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
St. Jude Medical, NIH
HeartFlow
These are my conflicts of interest. The FAME 2 Trial was sponsored by St Jude Medical.
FAME 2 was sponsored by St. Jude Medical 1

2. Fractional Flow Reserve
Proximal
Pressure (Pa)
Distal
Pressure (Pd)
FFR = Pd / Pa
during maximal flow Pa
Pd / Pa = 60 / 100
FFR = 0.60 Pd

3. FAME 2 Trial
Stable patients with 1, 2, or 3 vessel CAD evaluated for PCI with DES
n=1220
FFR in all target lesions
Randomized Trial
Registry
At least 1 stenosis with FFR ≤ 0.80 (n=888)
All FFR > 0.80
(n=322)
Randomization 1:1
The FAME 2 trial included stable patients with single, double or triple vessel coronary disease being evaluated for PCI with DES. This study was different from previous trials evaluating PCI in patients with stable CAD in that FFR was first measured across all lesions. By doing this, patients with angiographically significant CAD, but not hemodynamically significant (and therefore unlikely to be responsible for symptoms or to cause a future event) were not included in the randomized study. On the other hand, patients who did have at least one lesion in a major epicardial vessel with an FFR ≤0.80 were included, ensuring a significant ischemic burden in those randomized to FFR-Guided PCI or to MT. The primary endpoint was D, MI, or urgent revasc at 2 years.
PCI + MT MT MT
50% randomly assigned to follow-up
Primary Endpoint: Death, MI, Urgent Revascularization at 2 years

4. FAME 2 Trial Results % FFR-Guided PCI (n=447) MT (n=441) P-Value
Primary Endpoint
4.3
12.7
<0.001
Death
0.2
0.7
0.31
Myocardial Infarction
3.4
3.2
0.89
Urgent Revascularization
1.6
11.1
Free from Angina (1 month) 71 48 %
De Bruyne, et al. New Engl J Med 2012;367:

5. Results Quality of Life at 1 Month Angina (%) Utility Change
FFR-Guided PCI MT
p-value
Angina (%)
Class 0-1 89 71
<0.001
Class 2-4 11 29
Utility Change
0.054
0.003
The percent of patients with mild or no angina was significantly greater at one month in the FFR-Guided PCI arm. This resulted in a significantly greater change in utility from baseline to one month in the FFR-Guided PCI arm of compared to essentially no improvement (0.003) in the MT arm.

6. Cumulative Costs over 12 Months
$2,508
$5,485
100%
56%
11%
% of study population

7. FFR-Guided PCI Cost-Effectiveness
In-trial results $2,500 / QALY = $53,000 / QALY Three Year Projection $2,500 / QALY = $32,000 / QALY

8. Cost-Effectiveness CE Benchmarks: Hemodialysis ≈ $50,000 / QALY
WHO GDP std ≈ $150,000 / QALY
>$150,000 / QALY
$50K-150K / QALY
<$50,000 / QALY
Study
Comparators
CE Ratio
COURAGE
Angio-Guided PCI
vs Medical Therapy
≥ $168,000 / QALY
FAME 1
Angio-Guided PCI vs
FFR-Guided PCI
FFR-Guided PCI is Dominant (↓$ / ↑QALY)
FAME 2
FFR-Guided PCI vs Medical Therapy
$32,000 / QALY
To provide some context for our findings, shown on this slide is the traditionally accepted cutoff of $50,000 per QALY based on hemodialysis. Some have argued that this number is outdated and that a more appropriate cutoff would be the one proposed by the WHO for the US of $150,000 per QALY. Using these thresholds, one can conclude that any strategy falling above $150,000 per QALY is not likely to be accepted as CE, any strategy between $150,000 and $50,000 per QALY is likely to be considered CE and a strategy falling below $50,000 per QALY can be considered CE. The COURAGE trial, which compared an angio-guided PCI strategy to MT, found that the CE ratio was at least $168K/QALY if not higher, and therefore not CE. In the FAME 1 trial, we compared an angio-guide PCI strategy to an FFR-guided one and found that the FFR-Guided strategy was “dominant”, meaning it cost less money and improved outcomes. Now in FAME 2 we have shown that the cost-effectiveness ratio of an FFR-guided PCI strategy compared to MT is favorable at $32,000/QALY

9. Conclusion:
FFR-Guided PCI has higher initial cost than medical therapy.
The cost gap narrows >50% by one year.
Angina and quality of life are significantly improved by PCI.
FFR-Guided PCI appears to be economically attractive in cost-effectiveness analysis