FUTURE: Mortality Increase in the FFR Arm, Real or Casual?

The FUTURE study, testing the utility of functional revascularization by measuring the fractional flow reserve (FFR), was halted early by its safety committee due to an increased mortality rate at 1 year among patients guided by FFR.

In this unexpected unprecedented outcome, 17 patients in the FFR-guided group died at a year of follow-up, compared with 7 patients in the angiography-guided control arm.

At the time the trial was stopped, the difference in mortality among the 836 patients included in the analysis was significantly higher for the FFR arm (2% vs. 4%; p = 0.02).

While presenting the results at the American Heart Association Scientific Sessions 2016, the author of this study reported that the trial leaves more questions than answers, mainly because its early end precludes firm conclusions on the primary endpoint of all-cause mortality, acute myocardial infarction, repeat revascularization, or stroke. The difference in mortality may be a spurious finding.

FUTURE was a randomized study conducted at 31 centers in France with a planned enrollment of 1721 patients with multivessel disease. The working hypothesis was that FFR would be a useful treatment guide for angioplasty, surgery, or medical therapy, and would improve outcomes compared with traditional angiography-guided treatment.

Registry data have shown that FFR modifies the revascularization strategy in approximately 40% of patients, with an even higher percentage when considering patients without prior functional studies.

In FUTURE, the therapeutic strategy was altered as expected. In both the control and the FFR arm, there was no difference in the number of patients who underwent surgery, but the number of patients who received optimal medical therapy alone was significantly higher in the FFR arm, while the use of angioplasty was significantly less in this group.

In the FFR arm, 17% received optimal medical therapy, only 12% received surgery, and 71% underwent an angioplasty. In the angiography-guided arm, 9% received medical therapy, 12% received surgery, and 78% underwent an angioplasty.

A possible explanation for this excess in the mortality rate is that the FFR lowers the SYNTAX score (functional SYNTAX), which is why some patients might have not benefited from a myocardial revascularization surgery, for example. This is a reasonable theory; however, both study arms present a similar surgery rate.

Original title: Functional Testing Underlying Revascularization: The FUTURE Trial.

Presenter: Rioufol G et al.

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