MUNICH — Consistent with a previous analysis of the FUTURE trial, use of fractional flow reserve, compared with angiography, to guide treatment in patients with multivessel disease was linked to a twofold increased risk for death at 1 year.
The sponsor and data safety monitoring board halted the FUTURE trial after 938 patients — slightly more than half the targeted enrollment of 1,728 patients — were randomly assigned to FFR-guided or angiography-guided treatment, due to concern about excess mortality in the FFR-guided group, according to Gilles Rioufol, MD, PhD, from the Hospices Civils de Lyon in France.
Results from a safety analysis then confirmed a significantly increased mortality risk in patients whose treatment was guided by FFR vs. angiography (HR = 2.39; 95% CI, 1.05-5.43).
Furthermore, in the intention-to-treat analysis of 937 patients, the risk for the primary endpoint of a composite of all-cause death, MI, repeat revascularization and stroke did not differ significantly between the FFR-guided and angiography-guided treatment groups at 1 year (HR = 0.97; 95% CI, 0.69-1.36) or at 2 years (HR = 0.99; 95% CI, 0.75-1.3).
Additionally, in an analysis of the individual components of the primary endpoint, there were no differences between the angiography-guided and FFR-guided treatment groups in CV death, MI, stroke or unplanned revascularization. All-cause death, however, remained about twice as high in the FFR-guided group vs. the angiography-guided group (3.7% vs. 1.5%; HR = 2.34; 95% CI, 0.97-5.68), although the small numbers were not able to drive a significance in the primary outcome, according to Rioufol.
The demographic characteristics were well balanced between the two study groups, showing a higher-risk CV population, Rioufol noted. About 30% of all patients had diabetes, 20% had a history of MI and nearly half had an ACS at clinical presentation. Angiographic findings also confirmed a higher-risk population, with roughly 50% of the population having three-vessel disease and a SYNTAX score of about 18.
For patients who underwent FFR, only 2% experienced complications. The mean FFR was 0.77 and 43% of lesions had FFR greater than 0.8.
At discharge, patients in both groups had a high level of optimal medical therapy, Rioufol noted. All patients were on at least one antiplatelet agent and most were on ACE inhibitors and beta-blockers. Insulin use, however, was more common in the FFR group (13% vs. 8%; P = .03).
The therapeutic strategy in the angiography-guided group was dominated by PCI (79%), with only 12% of patients undergoing CABG and 9% continuing on optimal medical therapy alone. These rates were significantly different in the FFR-guided group, according to Rioufol, with nearly twice the number of patients being on optimal medical therapy alone (17%). The rate of CABG, however, was identical (12%) and the majority underwent PCI (71%).
In both groups, ad hoc PCI was performed in about 9 of 10 patients who underwent PCI, Rioufol noted.
“Since we didn’t have prior assessment of investigator strategy before FFR, we cannot show precisely how FFR affected the final treatment strategy on an individual basis,” he said.
In a prespecified subgroup analysis, there were no differences in the primary endpoint according to diabetes status or according to treatment decision, with patients treated with optimal medical therapy only in the FFR-guided group having outcomes that were at least as good as those for patients in the angiographically-guided group, according to Rioufol.
Nevertheless, outcomes were significantly worse in the FFR-guided group for patients with stable angina, with a nearly twofold increased risk for major adverse CV events. There was also a trend toward worse outcomes in FFR-guided patients with a SYNTAX score greater than 32.
The researchers also conducted an exploratory analysis of all-cause mortality to understand why more deaths occurred in the FFR-guided group, Rioufol noted.
“We observed that FFR patients had more severe disease with more three-vessel disease and very high SYNTAX score. Interestingly, diseased patients in the FFR group were more often treated with PCI and significantly more often had SYNTAX score above 32 in comparison with control patients,” he said.
“Taken together, these observations may then suggest that in stable patients with complex anatomy, FFR might indicate that PCI is the treatment choice instead of surgery.”
All-comer patients presenting with stable or stabilized angina referred for angiography were considered for inclusion in the multicenter, randomized, prospective, open-label, controlled FUTURE trial. The study was conducted at 31 sites in France and had a superiority design for demonstrating a 30% lower rate of major adverse CV events at 1 year in the FFR-guided group. The study only included patients with three-vessel or two-vessel disease, including in the left anterior descending artery, with possible ambivalence of treatment strategy.
In the FFR-guided group, only lesions with a measurement below 0.8 were included in stratification and all lesions with FFR above 0.8 were disregarded for treatment.
“Treatment decision based on FFR in all-comer multivessel disease patients did not demonstrate any improvement in primary endpoint at 1 year,” Rioufol said. “The FUTURE trial was prematurely halted because of excess all-cause mortality in the FFR group. The hypothesis to explain this mortality may involve a lower rate than expected of CABG in multivessel disease patients, a higher rate of PCI in severe patients with SYNTAX score above 32 and a higher rate of PCI.” – by Melissa Foster
Rioufol G, et al. Late-Breaking Science in Interventional Cardiology 1. Presented at: European Society of Cardiology Congress; Aug. 25-29, 2018; Munich.
Disclosure: The study was sponsored by Hospices Civils de Lyon. Rioufol reports no relevant financial disclosures.