FAME 2, Act 2: FFR-guided PCI keeps its lead at 2 years

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 - clinical trial

PCI guided by fractional flow reserve (FFR) in patients with stable coronary artery disease who were treated with second-generation drug-eluting stents and medical therapy reduced the need for urgent revascularization compared with medical therapy alone, according to two-year results from FAME 2.

The findings were published online Sept. 1 in the New England Journal of Medicine and presented at the European Society of Cardiology (ESC) meeting in Barcelona.

In 2012, Bernard De Bruyne, MD, PhD, of the Cardiovascular Center in Aalst, Belgium, and colleagues presented early findings from FAME 2 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2) at the ESC meeting in Munich. FAME 2 was designed to determine if FFR-guided PCI plus medical therapy was superior to medical therapy alone for reducing the rate of death, MI or urgent revascularization in patients with stable coronary artery disease. The trial used drug-eluting stents, the best medical therapy available and participants from 28 sites in Europe and North America.

Researchers stopped enrollment for FAME 2 prematurely, on Jan. 15, 2012, because of an excess of urgent revascularizations seen in the medical therapy group. They then presented findings up to the cutoff date at ESC.12. Those results gave PCI a significant advantage compared with medical therapy alone for avoiding urgent revascularizations.

The study included 1,220 patients with at least one stenosis with an FFR of 0.8 or less in a large epicardial artery. The patients were randomly assigned to FFR-guided PCI plus medical therapy or medical therapy alone. Patients with stenosis with an FFR of more than 0.8 were enrolled into a registry and received the best medical therapy available. The primary endpoint was a composite of death, MI or urgent revascularization at two-year follow-up.

At two years, 8.1 percent of the PCI group and 19.5 percent of the medical therapy alone group had a primary outcome event. In the registry group, the rate was 9 percent. The rate of urgent revascularizations was 4 percent in the PCI group and 16.3 percent in the medical therapy alone group, with no difference in the overall rate of death or MI between the two groups.

In the first seven days after randomization, the PCI group had a higher rate of primary events at 2.2 percent vs. 0.9 percent, mostly due to periprocedural MIs. Results favored the PCI group between eight days and two years for a primary event outcome (4.6 percent vs. 8 percent, for a relative risk reduction of 44 percent) and for urgent revascularization (3.6 percent vs. 15.6 percent, for a relative risk reduction of 79 percent).

“Severe angina was present in more than 90 percent of patients who underwent urgent revascularization, and in more than 40 percent of these patients, there was an increase in biomarkers or dynamic changes on electrocardiography, which are criteria for performing PCI according to both American and European guidelines,” the FAME 2 team wrote. “Therefore, urgent revascularization in our study should be considered a failure of the treatment to which the patient has been assigned.”

In an accompanying editorial, Jeffrey J. Rade, MD, of the University of Massachusetts Medical School in Worcester, recapped criticism of the decision to stop enrollment prematurely and publish early results. Critics argued many patients became cognizant of their angiographic findings, “a factor that could have lowered the threshold for revascularization in patients with FFR-positive stenoses in the medical-therapy group.”    

Rade pointed out that there was no significant between-group difference in mortality but there was evidence of a sustainable reduction in the need for urgent revascularization in the PCI group. “As the safety of both stents and the procedure to implant them continues to improve, it is entirely possible that PCI may eventually be shown to have a favorable effect on other hard end points as well,” he suggested.

St. Jude Medical funded the trial.