AHA: FFR-Guided Tx Raises Safety Concerns in FUTURE Trial

NEW ORLEANS -- After its premature termination, a French trial analyzing the role of fractional flow reserve (FFR) as guidance for the treatment of multivessel disease raised questions of the strategy's safety.

The FUTURE trial randomized patients to FFR- or angiography-guided strategies -- namely stenting, surgery, or optimal medical therapy -- but an unexpected excess of deaths in the FFR group within 12 months (17 versus seven in the standard angiography control group, 4% versus 2%, P=0.02) led the Drug Safety Monitoring Board to recommend ceasing recruitment when the investigators were only halfway to their goal of enrolling 1,721 patients.

Looking only at the 797 patients followed to the planned 1 year endpoint, all-cause death was no longer statistically significantly higher in the FFR cohort (P=0.07), Gilles Rioufol, MD, PhD, of France's Hospices Civils de Lyon, reported during a session for late-breaking trials at the annual American Heart Association meeting here.

He and his colleagues had started with a superiority trial design powered for 30% relative risk reduction in major adverse cardiovascular events with FFR at 1 year.

After halting, the FUTURE trial did not show a difference in the primary composite endpoint of 1 year all-cause mortality, MI, repeat revascularization, and stroke (15.1% for FFR versus 13.2% for angiography, HR 1.09, 95% CI 0.76-1.56).

Where do clinicians go from here?

"Assume FFR is safe," suggested discussant Herbert D. Aronow, MD, MPH, of Providence's Rhode Island Hospital and the Miriam Hospital.

He cited the reduction in percutaneous coronary intervention (PCI) and more frequent selection of optimal medical therapy alone as the treatment for FFR-guided cases.

"One would have to argue that performing more PCI would have led to a lower mortality rate. We know that 13 of the 17 deaths in the FFR arm underwent PCI, so we know it wasn't the change in treatment decision that lead to the excess [of deaths]. I believe this was chance," Aronow said.

Yet panelist C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center in Boston, noted a weakness of FFR that may undermine its perceived advantages.

"FFR doesn't measure stability," he said. "It assesses the amount of blockage but not the amount of activity within that plaque."

FUTURE was conducted at 31 centers in France. Participants had stable or stabilized angina and multivessel disease and underwent optimal medical therapy, PCI, or coronary artery bypass grafting.

The first randomization occurred in May 2013. In the trial, only FFR values that were found to be 0.80 or below (n=399) were considered significant and could be treated by coronary bypass or stenting. For the angiography group, that cutoff was 50% stenosis or more (n=398).