AHA 2016: Mortality rate with FFR-guided treatment of multivessel disease is unexpectedly high

Gilles Rioufol
Gilles Rioufol

The results of the FUTURE (Functional testing underlying revascularisation) trial indicate that the use of fractional flow reserve (FFR) to guide treatment—medical management, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)—in patients with multivessel disease may be associated with significantly higher mortality than the use of standard treatment (angiography).

Presenting the results of the study at the 2016 American Heart Association (AHA) scientific sessions (12–16 November, New Orleans, USA), Gilles Rioufol (Interventional Cardiology Department, Hospices Civils de Lyon, Lyon, France) reported that FFR has been shown to significantly decrease the SYNTAX score in one third of patients with multivessel disease “when only ≤0.80 FFR arteries are taken into account”. He added that the modality is recommended for guiding PCI in patients with multivessel disease (Class IIa recommendation; level of evidence B) but noted “whether FFR helps to decide among different treatment strategies—PCI, CABG or medical treatment only—remains unknown.”

Therefore, Rioufol and colleagues sought to determine if FFR helped “to guide treatment strategy and thereby improve clinical prognosis compared to traditional management”. In the study, patients with stable or stabilised angina and multivessel disease (>50% stenosis, including left anterior descending artery) were randomised to undergo FFR guidance or angiography guidance. The primary endpoint was the one-year composite rate of all-cause mortality, myocardial infarction, repeat revascularisation and stroke.

The aim was to enrol 1,721 patients from 39 centres, but Rioufol stated that an “unexpected excess” of mortality observed in the FFR group of first 836 patients enrolled prompted the study’s data safety and monitoring board (DSMB) to recommend that the trial be halted. He added that at 12 months, going by this interim safety analysis, the rate of all-cause death was 4% for the FFR group and 2% for the control group (p=0.02 for the comparison), commenting that cardiovascular death represented “72% of all deaths”. “The sponsor and the steering committee decided to follow the DSMB’s recommendation and stopped recruitment at 936 patients,” Rioufol explained.

According to the available data, with FFR-guided treatment, the use of medical treatment increased from 9% to 17%, the use of CABG was similar to that of standard therapy (12% in both groups), and the use of PCI decreased from 78% to 71%. Rioufol told Cardiovascular News that, given the premature halting of the trial, it is “difficult to have a definitive answer” as to why there was excess mortality in the FFR group but commented: “It seems possible that some complex patients (high SYNTAX score) could have been treated by PCI in the FFR group instead of perhaps CABG. Most of deaths were cardiovascular and almost all in the PCI treatment group. The majority of cardiovascular deaths were sudden cardiac death.”

However, data for the patients who reached the one-year follow-up point (398 in the control group and 399 for the FFR group) did not indicate a significant difference in the rate of all-cause mortality between groups: 3.9% for FFR vs. 1.8%  for angioplasty (p=0.11). Rioufol suggested that this may be a “by chance” finding but also noted that it may relate to the fact not all of the patient population had reached the one-year follow-up point (only 85%).

Regarding the implications of the study for future role of FFR in multivessel disease, he said: “In high SYNTAX patients with multivessel disease, functional revascularisation perhaps cannot ‘catch’ all of the prognostic information. Also, the burden of atheroma/complexity of lesions should also be integrated in the revascularisation strategy.”