FAME 2 -- FFR-guided drug-eluting stenting better than medical therapy in stable CAD

BARCELONA, Spain – Monday 1 September 2014: Fractional flow reserve (FFR)-guided drug-eluting stenting reduces death, myocardial infarction or urgent revascularisation, as compared to medical therapy in patients with stable coronary artery disease (CAD), according to the results of the FAME 2 trial presented for the first time today at ESC Congress by principal investigator Dr Bernard De Bruyne (Belgium).

Dr De Bruyne said: "Percutaneous coronary intervention (PCI) has been performed for more than 30 years. Nevertheless, its benefits in terms of 'hard endpoints' as compared to medical therapy (MT) have never been demonstrated in patients with stable CAD. Therefore, MT remains the preferred initial management strategy."

The Fractional flow reserve versus Angiography for Multivessel Evaluation 2 trial (FAME 2) compared contemporary PCI plus MT to MT alone in patients with stable CAD. 'Contemporary' refers to PCI guided by FFR and using second generation drug-eluting stents (DES). The predefined primary endpoint was a composite of death from any cause, nonfatal myocardial infarction (MI), or unplanned hospitalisation leading to urgent revascularisation during the first two years.

Between 15 May 2010 and 15 January 2012, FAME 2 enrolled 1 220 patients from 28 sites in Europe and North America in whom PCI with DES was planned. In contrast to most previous trials in patients with stable CAD, only those with a stenosis able to induce myocardial ischaemia as assessed by an FFR value ≤0.80 were included. These patients were randomised to either PCI + MT (n=447) or to MT alone (n=441). The remaining 332 patients were not randomised but followed-up in a registry and treated with MT.

Recruitment to the trial was interrupted prematurely because of a highly statistically significant between-group difference favouring PCI + MT. Today Dr De Bruyne reports on the primary endpoint after two years. The rate of death, MI, or urgent revascularisation at two years was lower with PCI than MT (8.1% vs 19.5%, hazard ratio [HR] 0.39, 95% confidence interval [CI] 0.26-0.57, p<0.001), driven by a lower rate of urgent revascularisation (4.0% vs 16.3%, HR 0.23, 95% CI 0.14-0.38, p<0.001). Dr De Bruyne said: "In patients with stable CAD the rate of death, MI, or urgent revascularisation at two years in those treated with FFR-guided PCI using contemporary DES was less than half of what it was in patients treated with MT alone."

Urgent revascularisations triggered by an MI or ischaemic electrocardiogram (ECG) changes were less frequent with PCI (3.4% vs 7.0%, HR 0.47, 95% CI 0.25-0.86, p=0.013), as were urgent revascularisations triggered by Canadian Cardiovascular Society (CCS) class IV angina (2.5% vs 10.7%, HR 0.22, 95% CI 0.11-0.42, p<0.001). Dr De Bruyne said: "Urgent revascularisations triggered by a myocardial infarction or ischaemic ECG changes were half as frequent with PCI plus MT than with MT alone."

In a landmark analysis, the rate of death or MI was lower in the PCI group than in the MT group after the landmark at seven days (4.6% vs 8.0%, HR 0.56, 95% CI 0.32-0.97, p=0.037). In registry patients, the rate of the primary endpoint remained low (9.0%) and similar to the rate observed in the PCI group.

Dr De Bruyne said: "Beyond seven days from randomisation, PCI plus MT significantly reduced the rate of death or MI when compared to MT alone. More than 25% of stable CAD patients scheduled for PCI on the basis of clinical and angiographic data have no stenosis capable of inducing myocardial ischaemia as assessed by FFR and have a favourable clinical outcome at two years with MT alone, which is similar to patients with at least one significant stenosis treated with PCI plus MT."

He concluded: "In patients with stable CAD and at least one haemodynamically significant stenosis, FFR-guided PCI plus medical therapy is associated with a 61% reduction in major adverse cardiac events after two years."