Should we just go with the flow? Fractional flow reserve-directed PCI and the FAME-2 trial

Published - Written by John Staples

Most of us don’t give much thought to the luminal appearance of the drainpipe in our kitchen sink. Why worry about it as long as the water’s flowing well? It’s when the flow slows to a trickle that we think about calling a plumber.

Flow is also of primary importance in the coronary arteries. Although an angiogram captures the luminal appearance of a stenosis, it may not reflect the degree to which coronary blood flow is impeded. One measure of the hemodynamic significance of a stenotic lesion is the fractional flow reserve (FFR). The FFR is the ratio of post-stenosis coronary arterial pressure to aortic pressure, measured during adenosine-induced hyperemia. In a normal artery these two pressures are equal (i.e. FFR = 1.0), while a stenotic arterial segment with an FFR <0.75 is considered functionally significant.

In this week’s NEJM, Dr. Bernard De Bruyne (Cardiovascular Center Aalst, Belgium) and colleagues report on a trial that used FFR to identify hemodynamically significant coronary stenoses. The Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME-2) trial enrolled 888 patients with stable CAD and at least one coronary artery stenosis with an FFR <=0.80. Enrollees were randomized to receive FFR-guided percutaneous coronary intervention plus optimal medical therapy (PCI+OMT) or optimal medical therapy (OMT) alone. The pre-specified primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, and unplanned hospitalization leading to urgent revascularization.

After a mean follow-up of only 7 months, the data safety and monitoring board recommended early termination of the trial as the PCI+OMT patients were dramatically less likely to reach the primary endpoint (4% vs 13%; HR 0.32, 95%CI 0.19-0.53). This difference was driven almost entirely by a lower proportion of urgent revascularizations in the PCI+OMT group.

Editorialist Dr. William E. Boden (Albany Medical College, NY) notes that the results of the FAME-2 trial echo the results of the COURAGE trial. In both studies, adding PCI to OMT reduced the risk of unplanned revascularization but did not significantly reduce myocardial infarction or death. Since selection bias might influence treatment decisions in an unblinded trial, such benefits might not be sufficient to justify the routine use of FFR to guide revascularization decision-making in stable CAD.

“There is something intuitively appealing about opening up a partially-blocked pipe,” says cardiologist and NEJM Executive Editor Dr Gregory D. Curfman, “But FAME-2 suggests that the benefits of revascularization in stable coronary disease may be modest, even when fractional flow reserve is used to identify hemodynamically significant targets.”

Is the idea that PCI can be life-saving in patients with stable CAD still flush with promise? Or is it slowly slipping down the drain? The controversy is likely to continue until more definitive trials can be completed. Fortunately, as Dr. Boden points out, such trials are already in the pipeline. Stay tuned.