FAME 2: FFR-Guided PCI ‘Economically Attractive’ vs. Medical Therapy Alone

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In patients with abnormal fractional flow reserve (FFR), percutaneous coronary intervention (PCI) is initially more expensive than medical therapy alone. However, the money saved by avoiding repeat revascularization in the year after treatment substantially narrows that gap, according to findings published online August 14, 2013, ahead of print in Circulation.

Cost-effectiveness data from FAME 2 (FFR-Guided Percutaneous Coronary Intervention Plus Optimal Medical Therapy vs. Medical Therapy Alone in Patients with Stable Coronary Artery Disease) were previously presented in October 2012 at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in Miami Beach, FL.

FAME 2 enrolled more than 1,200 patients with stable CAD and angiographically significant stenoses. Patients found to have at least 1 flow-limiting lesion (FFR ≤ 0.8) were randomized to optimal medical therapy with (n = 447) or without (n = 441) FFR-guided PCI. The study was halted early after interim data showed that FFR-guided patients had substantially fewer events related to the primary composite endpoint of all-cause death, MI, or urgent revascularization (4.3% vs. 12.7%; HR 0.32; 95% CI 0.19-0.53; P < 0.001).

For the current study, William F. Fearon, MD, of Stanford University Medical Center (Stanford, CA), and colleagues, looked at how assignment to PCI vs. medical therapy alone impacted cost-effectiveness and quality of life in FAME 2.

Repeat Revascularization Savings Add Up

Initial costs of the index hospitalization were $6,027 higher for PCI. But over the course of 1 year, follow-up costs were higher for medical therapy, narrowing the gap to $2,883 (table 1).

Table 1. FAME 2: Cost by Treatment Assignment


(n = 447)

Medical Therapy
(n = 441)

P Value

Index Procedure



< 0.001




< 0.001

Total at 12 Months



< 0.001

The early disadvantage for PCI related primarily to device costs, professional fees, and hospitalization and cath lab costs. During follow-up, PCI saved money by reducing the need for repeat revascularization, including PCI (urgent or nonurgent; $11,166 per case) and CABG ($27,207 per case; table 2).

Table 2. Cumulative Costs of Repeat Revascularization at 12 Months


(n = 447)

Medical Therapy
(n = 441)

Nonurgent PCI



Urgent PCI







Patient utility, assessed using the EQ-5D health survey, was more improved at 1 month vs. baseline by FFR-guided PCI than by medical therapy (0.054 vs. 0.001 units; P < 0.001).

In addition, the incremental cost-effectiveness ratio of PCI was $36,000 per quality-adjusted life-year. It was below $50,000/QALY in 80% of 10,000 bootstrap replications and below $100,000/QALY in 99.5% of replications.

“In patients with symptomatic stable coronary artery disease, PCI in the setting of an abnormal FFR improves angina and quality of life, and appears to be economically attractive compared with best medical therapy assuming the benefit of PCI lasts longer than 1 year,” the researchers conclude.

FFR Pinpoints Lesions Most Likely to Benefit

Dr. Fearon told TCTMD in an e-mail communication that the FAME 2 results “should encourage greater adoption of FFR,” because routine application of the test can help identify patients and lesions most likely to benefit from PCI.

However, “[a]n abnormal FFR should by no means force an operator to perform PCI,” Dr. Fearon stressed, adding, “One always needs to incorporate the clinical scenario and good judgment, as well as the FFR result, into one's treatment decision.”

For example, diffuse disease may fare better with medical therapy or even CABG than with focal PCI, and a lesion located in a small side branch with tight ostial narrowing may not warrant PCI, he said.

Dr. Fearon cited FAME 2’s early end as its greatest limitation. To conduct the current analysis, researchers had to make assumptions about the durability and cost differences over time, he said. “However, these were conservative assumptions based on the literature, and the results were robust in sensitivity analyses.” Though additional follow-up data are expected, he noted, “a large proportion of patients crossed over from medical therapy to PCI once enrollment was discontinued, which may affect the longer term results.”

Also in an e-mail communication, Kishore J. Harjai, MD, of Geisinger Wyoming Valley (Wilkes-Barre, PA), reported being unsurprised that “the clinical benefit of PCI—less angina, better quality of life and reduced repeat revascularization—translated into cost-effectiveness. By performing PCI only in functionally significant lesions, the FAME 2 investigators weeded out those lesions which are visually severe but do not benefit from revascularization.”

The COURAGE trial, which also compared optimal medical therapy with or without PCI in stable CAD patients, failed to show the cost-effectiveness of angiographically-guided PCI. But in FAME 2, the strategy differed by being FFR-guided and was thus cost-effective, he noted.

Time to Adjust Appropriate Use Criteria?

Importantly, the new “findings raise a controversy about appropriate use criteria (AUC) for PCI. More than three-quarters of patients in FAME 2 had angina class 2 or less. FFR-guided PCI is considered ‘inappropriate’ or ‘uncertain’ by the AUC in such patients,” Dr. Harjai commented. “I urge the American College of Cardiology to consider an urgent revision to AUC for this clinical scenario.”

Dr. Harjai reported that FFR is already a “huge” part of his own practice and, based on the current data, “should absolutely and immediately lead to more FFR utilization in stable, intermediate-severity lesions.” Cost-effectiveness, he added, is a “moving target.” Lower acquisition costs of DES, availability of new devices that further reduce revascularization, and development of noninvasive FFR testing may all change the equation.


Fearon WF, Shilane D, Pijls NHJ, et al. Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary disease and abnormal fractional flow reserve. Circulation. 2013;Epub ahead of print.



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Caitlin E. Cox is News Editor of TCTMD and Associate Director, Editorial Content at the Cardiovascular Research Foundation. She produces the…

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  • The study was sponsored by St. Jude Medical.
  • Dr. Fearon reports receiving institutional research support from St. Jude Medical.
  • Dr. Harjai reports being CEO and cofounder of AUCPortal.org.