August 28th, 2012
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 stenosis, defined as FFR 0.80 or less, were randomized to FFR-guided PCI plus medical therapy or medical therapy alone. Patients whose stenoses all had FFRs over 0.80 were observed in a registry and received best medical therapy.
The trial was stopped early, after enrollment of 1220 patients (888 in the randomized portion and 332 to the medical therapy registry), 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 that received optimal medical therapy alone. FAME 2 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 2 were not at very high risk.
- The short follow-up period (mean, 7 months) did not leave enough time for the risk for 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.”
More FAME 2 coverage: