FAME II: FFR Pinpoints Stable CAD Patients Who Need PCI in Addition to Medical Therapy

PARIS, France—Fractional flow reserve (FFR) measurements help identify which patients with stable coronary artery disease (CAD) cannot rely solely on optimal medical therapy (OMT) and therefore  require percutaneous coronary intervention (PCI), according to preliminary results from the FAME II trial presented in a late-breaking session at EuroPCR on Tuesday, May 15, 2012.

The advantage offered by FFR in terms of reducing repeat revascularization is so striking, in fact, that the trial's Data and Safety and Monitoring Board (DSMB) advised stopping patient recruitment early, reported investigator Bernard De Bruyne, MD, PhD, of Cardiovascular Center Aalst (Aalst, Belgium).

Choosing When to InterveneFAME II builds on the original FAME (Fractional Flow Reserve versus Angiography for Guiding PCI in Patients with Multivessel Evaluation) trial, which showed in nearly 1,000 patients with multivessel disease that FFR guidance during PCI improves clinical outcomes through 2 years over angiographic guidance alone.

In the newer study, researchers sought to understand whether FFR guidance could help identify which patients with stable CAD stood to benefit from PCI. All subjects were slated for DES implantation in up to 3 vessels at the time of enrollment. Based on their FFR results, patients were stratified to different treatment strategies:

  • Those with FFR > 0.80 received OMT alone, with half randomly assigned to follow-up in a registry (n = 131)
  • Those who had at least 1 stenosis with FFR ≤ 0.80, indicating hemodynamic significance, entered into a randomized comparison of OMT with (n = 352) or without PCI (n = 339)

As of November 2011, when the DSMB made its recommendation, a total of 965 patients had enrolled. Demographic factors and disease history were similar between the randomized and registry patients, as was clinical presentation. But within the randomized cohort, the need for urgent or any revascularization was higher at 1 year in patients assigned to OMT alone rather than OMT plus PCI (table 1), showing the value of FFR in identifying patients in need of revascularization.

Table 1. FAME II: Preliminary Results in the Randomized Cohort at 1 Year


OMT Alone
(n = 339)

(n = 352)

HR (95% CI)

Log-rank P Value

Urgent Revascularization



11.2 (2.62-47.9)

< 0.0001

Any Revascularization



7.63 (3.24-18.0)

< 0.0001

Importantly, outcomes were equivalent between the registry patients—who were given OMT alone after being cleared of having hemodynamically significant lesions—and those randomized to OMT plus PCI (P = 0.71 for urgent and P = 0.54 for any revascularization).

Dr. De Bruyne did not report data on the trial's primary endpoint, the composite of all-cause death, MI, or unplanned hospitalization with urgent revascularization.

Treat Ischemia, Not Lesions

Large randomized trials have thus far failed to show that PCI can affect clinical outcomes in patients with stable CAD, Dr. De Bruyne noted. But because the decision to revascularize is often based on the angiographic appearance of lesions, “it is very likely that in many previous trials [of] patients with non-acute CAD, a sizable proportion of patients without ischemia has been included.” FAME II researchers sought to address this confusion, he said.

Discussant David R. Holmes Jr, MD, of the Mayo Clinic (Rochester, MN), said the new findings are strong enough to influence practice. FAME II “is a terribly important trial that extends observations that we've previously had and identifies the fact that we still should be treating ischemia, not lesions,” he said, suggesting that FFR should enter into the decision-making process early. “It's a groundbreaking trial.”

Franz-Josef Neumann, MD, of the Heart Center (Bad Krozingen, Germany), agreed. “FAME II adds to the growing body of evidence that FFR is an appropriate tool to assess the indication for PCI,” he commented following the presentation. Further data from FAME II, he added, “may confirm that contemporary PCI with optimized pharmacotherapy can be performed with a very low peri-interventional risk,” possibly ameliorating concerns that had been raised by the COURAGE trial.

In addition, the fact that 28% of patients had FFR > 0.80 indicates “that we have to be very careful with history taking prior to coronary angiography and we should perform functional testing in all of these patients,” Dr. Neumann concluded.


De Bruyne B. FFR-guided PCI plus optimal medical treatment versus optimal medical treatment alone in patients with stable coronary artery disease (FAME 2 trial): Preliminary results of cohort A. Presented at: EuroPCR; May 15, 2012. Paris, France.



  • FAME II is supported by St. Jude Medical.
  • Dr. De Bruyne reports having research contracts with and serving as a consultant.
  • Drs. Holmes and Neumann reported no relevant conflicts of interest.

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