FAME 2: Can FFR Save PCI From Medical Therapy?

Two sharply divergent views have developed about the value of fractional flow reserve (FFR) in PCI. FFR advocates think the new technology can help identify ischemic lesions that will benefit from PCI, thereby helping to salvage or enhance the reputation of PCI. FFR skeptics think that optimal medical therapy is still the preferred option for most patients with stable angina. Both sides find evidence to support their view in the FAME 2 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) trial presented at the ESC and published simultaneously in the New England Journal of Medicine.

The FAME 2 investigators sought to show that patients who had ischemic lesions as determined by FFR would benefit from the addition of PCI to the best available medical therapy. Patients with stable coronary artery disease under consideration for PCI underwent FFR. Patients who had at least one functionally significant lesion, defined as FFR < .80, were randomized to FFR-guided PCI plus medical therapy or medical therapy alone. Patients with no ischemic lesions were observed in a registry and received best medical therapy.

The trial was stopped early after enrollment of 1,220 patients (888 in the randomized portion and 441 to the medical therapy registry)– about half the number of intended patients– because of a significant reduction in the primary endpoint (the composite of death, MI or urgent revascularization) in the PCI group:

  • 4.3% in the PCI group versus 12.7% in the medical therapy group (HR for PCI 0.32, CI 0.19-0.53, p<0.001)
  • 3% of patients in the registry had a primary endpoint event

There was no difference between the groups in the rate of death or MI. The difference in the primary endpoint was driven entirely by the lower rate of urgent revascularization in the PCI group:

  • 0.7% in the PCI group versus 9.5% in the medical therapy group (HR 0.07, CI 0.02-0.22)

The FAME  2 investigators wrote that PCI was found to be beneficial in their trial, but not in previous trials like COURAGE, because of the demonstrated presence of ischemia in their randomized population. In addition, they noted that despite receiving the best medical therapy available, there were significantly more unplanned hospitalizations with urgent revascularizations in the medical therapy group.

A very different view of the trial is presented in an accompanying editorial by William Boden, the principal investigator of the COURAGE trial, who asks: “Which Is More Enduring– FAME or COURAGE?” The first FAME trial compared angiographic-guided PCI to FFR-guided PCI but did not include a COURAGE-type arm which received optimal medical therapy alone. FAME II was designed to address that question, writes Boden, but it should not be interpreted to mean that FFR-guided PCI is superior to optimal medical therapy. Boden makes the following points:

–There were few “hard” events in FAME 2 and urgent revascularization could be performed without objective evidence  of ischemia or positive biomarkers.

–Since the trial was unblinded, “investigators may have had a lower threshold for recommending revascularization” for patients in the medical group.

–Patients in the FFR group did not have noninvasive testing demonstrating ischemia, so some may have had preserved myocardial perfusion.

–Patients in FAME II were not at very high risk.

–The short followup period (mean followup of 7 months) did not leave enough time for the risk of restenosis to fully emerge.

Boden is highly critical of the early termination of the study, writing that it leaves “more questions than answers…. but the only enduring finding of the FAME 2 trial appears to be that  of a reduced short-term rate of unplanned revascularization with FFR-guided PCI, with little evidence of long-term, incremental benefit on prognostically important clinical outcomes.”

Republished with permission from CardioExchange, a NEJM group publication.


  1. One Patient. says

    One lay reflection from a pt. who had a single pci in the lcx three years ago. Bias assumed, since we will almost always favor the decisions we made (unless they take us out or do other harm).

    I had an excellent result re: symptom relief that has lasted, and my interventionist was very clear that sx relief was the most that pci was then known to achieve for some number of pts. I was well informed of the risks.

    For me, the alleviation of sx’s also made it easier to get back to intensive exercise quickly (I was already an active person) and certainly with less anxiety (founded or not). I suspect the “mental” aspects may not be well captured by the usual M&M stats, as important as they are, and has a number of related impacts that concern qualifity of life.

    I understand that medical therapy might have achieved the same result. But, given the amount of activity I was already doing, along with already normal BP, well controlled :LDL very healthy diet, and related, PCI certainly seems in retrospect to have been the right way to go.

    The usual lesson here, I think, about what the big studies do and do not tell us re: choices for particular pts.

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