Presenter: Bernard De Bruyne | see Discussant report
List of Authors: Dr. Bernard De Bruyne / Belgium
Co-authors: William F Fearon, Nico HJ Pijls, Emanuele Barbato, Pim AL Tonino, Bindu Kalesan, Peter Juni, for the FAME II study group.
In patients with clinically stable coronary disease, percutaneous coronary intervention (PCI) improves anginal symptoms, but has not been shown to affect clinical outcomes such as death, non-fatal myocardial infarction and the need for urgent revascularisation.
The main objective of the FAME II trial is to compare the clinical outcomes, of FFR-guided contemporary PCI plus optimal medical treatment (OMT) versus OMT alone in patients with stable coronary disease, invasively established ischemia-inducing stenoses in large coronary arteries, in whom both PCI and medical treatment could be considered.
The FAME II trial is a multi-continental, randomized trial with an ‘all comers’ design. Consecutive patients with stable clinical condition and one-, two, or three-vessel coronary artery disease amenable for PCI with drug eluting stents were considered for participation. First, fractional flow reserve (FFR) was measured in all potential target stenoses. If at least one stenosis appeared to be hemodynamically significant, patients were randomised to receive either PCI+OMT or OMT alone. If none of the target stenoses appeared to be significant (all FFR values>0.80), patients were not randomized but treated by OMT and included in a registry (with 50% of registry patients randomly selected for follow-up). The primary endpoint was the 24-month rate of overall MACE defined as all cause death, documented myocardial infarction (MI), or unplanned hospitalization leading to urgent revascularization. The secondary endpoints included, non-urgent revascularization procedures, functional class, number of anti-anginal medication, and stroke.
On October 20, 2011, after inclusion of 691 patients in the randomized trial (42.3% of the planned number of patients) and 264 patients in the registry, the independent data and safety monitoring board recommended stopping recruitment because of a highly significant difference between groups for the primary outcome. The average number of lesions per patient was 1.9 (SD 1.1) in the randomized trial and 1.5(SD 0.8) in the registry. In the trial, 63% of patients were in CCS class II or III and the average FFR value of hemodynamically significant lesions was 0.68 (SD 0.15).The compliance to OMT was high and similar in both arms. There was a more than fourfold increase in the hazard of MACE in patients randomised to OMT alone (8.0% vs 2.0%; hazard ratio [HR] 4.36 [95% CI 1.90 to10.03]), which was driven by a an increase in the hazard of unplanned hospitalization with urgent revascularization (5.9% vs 0.6%, HR 11.20 [95%CI 2.62-47.92]). There was no difference in MIs (1.4% versus 1.8%) nor in death (0% versus 0.3%). Non-urgent revascularisations were less frequent in the PCI+OMT than in the OMT alone group (1.1% vs 6.2%). In patients without hemodynamically significant lesions included in the registry the number of major adverse cardiac events remained low (0.8%).
In patients with stable coronary artery disease and at least one stenosis with an FFR≤0.80, OMT alone was associated with a more than fourfold larger hazard of major adverse cardiac events than FFR-guided PCI with drug-eluting stents plus OMT. This difference was driven by a difference in unplanned hospitalization with urgent revascularisation. In contrast, in patients with hemodynamically non-significant stenoses (FFR>0.80), OMT alone was associated with a favourable clinical outcome. The complete results of FAME II will be presented at the meeting.
Discussant: Frans Van de Werf | see Presenter abstract