Fractional Flow Reserve Versus Angiography for Multivessel Evaluation - FAME
Contribution To Literature:
The FAME trial showed that FFR-guided PCI is associated with lower MACE rates and resource utilization compared with angiography-guided PCI in patients with multivessel disease.
Although percutaneous coronary intervention (PCI) of ischemia-causing lesions is associated with better outcomes, it is often hard to determine the exact lesion causing ischemia in patients with multiple stenoses. The FAME trial sought to determine if fractional flow reserve (FFR) guidance of PCI would be associated with better outcomes in patients with multivessel disease.
Patients Screened: 1,905
Patients Enrolled: 1,005
Mean Follow Up: 1 year, 5 years
Mean Patient Age: 64.5 years
Mean Ejection Fraction: 57%
- Patients with stenoses of >50% in at least two of the three major coronary arteries
- Lesions amenable for stenting
- Left main disease or previous bypass surgery
- ST-elevation MI with creatine kinase >1000 U/L within the last 5 days
- Cardiogenic shock
- Life expectancy <2 years
- Contraindication to drug-eluting stents
- Pregnant patients
- Extremely tortuous or calcified coronary arteries
Incidence of MACE, defined as death, MI, or need for repeat revascularization at 1 year
- Death at 1 year
- MI at 1 year
- MACE at 30 days and 6 months
- Revascularization at 1 year
- Functional class at 1 year
- Number of antianginal medications used
- Health-related quality of life, as measured by EuroQOL-5D
- Procedure time
- Amount of contrast used during the procedure
- Cost of the procedure
Patients with multivessel disease, in whom a decision was made to stent all stenoses >50%, were randomized to either routine angiography-guided PCI, or FFR-guided PCI, in which FFR was measured in all significant stenoses, with stenting only of those lesions with an FFR ≤0.8. FFR was measured using a Pressure Wire (Certus Wire, RADI Medical Systems).
All patients in the FFR-PCI group, and 97% of the patients in the PCI group, received drug-eluting stents (either everolimus, sirolimus, or paclitaxel-eluting). Hyperemia was induced by intravenous adenosine 140 mcg/kg/min in the femoral vein. All patients received aspirin and clopidogrel for 1 year. Beta-blockers (77%), statins (81%).
A total of 1,005 patients were randomized, 509 to FFR-guided PCI, and 496 to angiography-guided PCI. Baseline characteristics were fairly similar between the two groups. About 33% of the patients presented with unstable angina, about 27% of the patients had undergone prior PCI, and about 27% of the patients had an ejection fraction of 50% or less. The mean number of indicated lesions was 2.8 per patient, with a mean reference vessel diameter of 2.5 mm, and a mean stenosis severity of 61%. Only about 3-4% of the lesions were total occlusions.
FFR was successfully measured in 94% of the lesions, and of the indicated lesions, only about two-thirds (67%) had an FFR ≤0.8. As a result, the mean number of stents was significantly lower in the FFR arm compared with the routine management arm (1.9 vs. 2.7, p < 0.001). Also, as expected, FFR of ischemic lesions was lower than FFR of non-ischemic lesions (0.60 vs. 0.88).
The mean procedure time was similar between the two arms (71 vs. 70 minutes), but the amount of contrast used was significantly lower in the FFR arm (272 vs. 302 ml, p < 0.001). The cost of materials for the procedure was also significantly lower in the FFR arm ($5,332 vs. $6,007, p < 0.001), and the length of hospital stay tended to be shorter as well (3.4 vs. 3.7 days, p = 0.05).
The incidence of major adverse cardiac events (MACE) at 1 year was significantly lower in the FFR arm compared with the routine management arm (13.2% vs. 18.3%, p = 0.02). The incidence of death (1.8% vs. 3.0%, p = 0.19), myocardial infarction (MI) (5.7% vs. 8.7%, p = 0.07), and coronary artery bypass grafting or re-PCI (6.5% vs. 9.5%, p = 0.08) at 1 year was similar between the two arms. The number of patients who were angina free at 1 year was also similar between the two arms (81% vs. 78%, p = 0.2). The quality of life, as measured by the EuroQOL-5D, was similar between the two arms as well (p = 0.65).
Five-year results: MACE for FFR vs. routine management: 28% vs. 31%, relative risk 0.91, 95% confidence interval 0.75-1.10; p = 0.31, mortality: 9% vs. 10%, p = 0.5; MI: 9% vs. 12%, p = 0.24; repeat revascularization: 15% vs. 17%, p = 0.49. There was a significant interaction with gender (p = 0.03); MACE was superior for FFR in males.
FFR immediately post-PCI (residual FFR burden) was measured in approximately two-thirds of the patients (median 0.9). At 2 years, the risk of vessel-related death, MI, or revascularization was lowest in patients with a post-PCI FFR of 0.92 or higher, primarily driven by a reduction in the need for revascularization.
The results of the FAME trial indicate that FFR-guided PCI is associated with a significantly lower incidence of MACE compared with routine angiography-guided PCI in patients with multivessel disease, without a significant increase in the procedure time and with lower costs and resource utilization. These results also indicate that routine use of FFR may deem more than a third of “significant” angiographic stenoses as non-significant (FFR ≥0.8), thus minimizing PCI due to the oculo-stenotic reflex. Results appear durable up to 5 years of follow-up in these patients, with no overall excess in MI, mortality, or revascularization in FFR-guided patients, suggesting that an FFR-guided strategy is likely safe and cost-effective.
The results of this trial are certainly interesting, but further trials are necessary to validate these findings before FFR can be considered for routine use in patients undergoing multivessel PCI. Moreover, most operators have limited experience with FFR, in contrast to the FAME investigators, who have extensive experience with FFR technology and its applications. Therefore, the benefits and applicability of FFR in routine practice may be diminished as a result of errors and higher complication rates.
The results of this trial are also similar to the nuclear substudy of the COURAGE trial, where PCI was associated with better outcomes compared with medical management in stable angina only if there was demonstrable ischemia on a nuclear stress test. FFR is a functional test for ischemia, with good relation to nuclear imaging, and thus the combination of these studies would suggest that PCI is beneficial only in stenoses that are associated with ischemia.
Presented by Dr. Zsolt Piroth at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2016), Washington, DC, October 29, 2016.
van Nunen LX, Zimmermann FM, Tonino PA, et al., on behalf of the FAME Study Investigators. Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial. Lancet 2015;Aug 30:[Epub ahead of print].
Presented by Dr. Nico H.J. Pijls at the European Society of Cardiology Congress, London, August 30, 2015.
Presented by Dr. Nico H.J. Pijls at the Transcatheter Cardiovascular Therapeutics meeting (TCT 2008), Washington, DC, October 2008.
Tonino PA, De Bruyne B, Pijls NH, et al., on behalf of the FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-24.
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