Fractional flow reserve (FFR)-guided PCI plus medical therapy compared with medical therapy alone decreased the need for urgent revascularization in patients with coronary artery disease (CAD), FAME 2 trial researchers reported Aug. 28 at the European Society of Cardiology Congress in Munich. The study was published simultaneously in the New England Journal of Medicine with an editorial that concluded the findings have resulted in more questions than answers.
Bernard De Bruyne, MD, PhD, of the Cardiovascular Center in Aalst, Belgium, and colleagues designed the FAME 2 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) study as an all-comers trial to determine whether FFR-guided PCI plus medical therapy was superior to medical therapy alone in reducing the rate of death, MI or urgent revascularization in patients with stable coronary disease. The trial used drug-eluting stents, the best medical therapy available and participants from 28 sites in Europe and North America.
In the first FAME trial, patients assigned to an FFR-guided PCI treatment group had a lower two-year rate of death or MI than patients in an angiographically guided PCI group. But FAME did not include a comparison group assigned to the best medical therapy, which De Bruyne et al described as the preferred initial treatment for patients with stable CAD.
FAME 2 enrolled patients with stable CAD with at least one functionally significant stenosis assessed by measuring FFR. The patients were randomly assigned to the FFR-guided PCI plus the best available medical therapy group or the best available medical therapy alone group. Patients with stenosis with an FFR of more than 0.80 were enrolled into a registry and received the best medical therapy available. The primary endpoint was a composite of death, MI or urgent revascularization for a projected two-year follow-up.
The researchers stopped the trial on Jan. 15, because of a significant difference in the incidence rates of the primary endpoint between the two study groups. The enrollment totaled 1,220 patients.
Of the 888 patients with at least one significant stenosis, 447 were randomized to the FFR-guided PCI group and 441 received the best medical therapy available. Another 332 patients were enrolled in the registry and received medical therapy. The mean follow-up was 213 days for the PCI group, 214 days for the medical therapy alone group and 206 days for the registry group.
Results showed that the PCI group compared with the medical therapy alone group had a lower rate of primary endpoint events, at 4.3 percent vs. 12.7 percent. Neither the rate of death from any cause nor the MI rate differed significantly between the groups. But the PCI group had a significantly lower rate of urgent revascularizations, at 0.7 percent vs. 9.5 percent for the medical therapy group. Only four patients in the PCI group underwent urgent revascularization triggered by MI or unstable angina with evidence of ischemia on an echocardiography (ECG) compared with 23 patients in the medical therapy group.
“The difference between the two strategies was driven by a factor of 13 in the need for urgent revascularization in the medical therapy group,” De Bruyne and colleagues wrote. “In the case of half of these urgent revascularizations, the need for the procedure was triggered by an increase in biomarker levels, ischemic changes on ECG or both.”
The short follow-up in the study was a limitation, the authors acknowledged, and although the trial was randomized there was the possibility of selection bias in physicians’ decisions to revascularize patients.
William E. Boden, MD, of the Albany Medical Center in Albany, New York, also highlighted those limitations in an accompanying editorial. “[T]he follow-up period was probably too short for restenosis to emerge; a longer follow-up might have narrowed the difference in the rates of unplanned revascularization between the two groups,” he wrote.
Bowen pointed out that FAME was similar to COURAGE, both of which showed PCI reduced the need for revascularization but did not show a benefit with death or MI. FFR-guided PCI offers promise as more clinically effective than visually directed PCI, he added.
“Unfortunately, the early termination of the FAME 2 trial before full enrollment and follow-up were achieved, the neutral effects on the rate of death and myocardial infarction and the lack of a significant, sustained treatment effect on the reduction