Fractional flow reserve (FFR), calculated using a coronary presure wire, is an index of the physiological significance of a coronary stenosis and is defined as the ratio of maximal blood flow in a stenotic artery to normal maximal flow. FFR in a normal artery is 1.0 – a value <0.80 identifies ischaemia causing lesions with a diagnostic accuracy of 90%, is more specific than that from myocardial perfusion studies and has a better spatial resolution. In patients with multivessel disease (MVD), identifying a percutaneous coronary intervention (PCI) approach allowing targeted use of stents whilst achieving relief of myocardial ischaemia could both improve clinical outcomes and decrease health costs.
The FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) Trial involved 1005 patients from 20 centres in the United States and Europe. This randomised trial compared treatment with FFR in addition to angiography with treatment guided by angiography alone for patients with MVD for which PCI was deemed appropriate. FFR cannot be performed in a totally occluded artery and a default FFR value of 0.5 was recorded for such vessels. The primary end-point was the rate of major adverse cardiac events (MACE) at 1 year. These were a composite of death, non-fatal MI and any repeat revascularisation. Secondary end-points included functional class at 1 year and the number of anti-anginal medications at 1 year. Quantitative coronary angiography was performed offline and the SYNTAX score was used to assess the extent and severity of coronary disease. The mean (+/- SD) number of indicated lesions/patient was 2.7 (+/-0.9) in the angiography group and 2.8 (+/-1.0) in the FFR group (p = 0.34). The number of stents used/patient was 2.7 (+/-1.2) and 1.9 (+/- 1.3) respectively (p<0.001). The 1 year event rate was 18.3% in the angiography arm and 13.2% in the FFR group (p=0.02). 78% of patients were free of angina at 1 year in the angiography arm compared to 81% in those treated with FFR (p=0.20).
Whilst this study was well designed there are several limitations. Little information is given on peri-procedural pharmacotherapy including pre-treatment with thienopyridines, use of antithrombin and glycoprotein IIb IIIa inhibitors. Peri-procedural MI was based on an elevation of CK-MB > 3 times and development of Q waves on the ECG but did not include troponin measurement which is surprising for a trial which enrolled from January 2006-September 2007. The rate for peri-procedural MI in the conventional treatment arm would appear to be quite high and in the order of 7.5%. Nonetheless, the reduction in clinical events seen is significant and impressive, and if the results can be reproduced in trials in less-experienced centers, then a change in practice may well result.
· Tonino PAL, De Bruyne B, Pijls NHJ et al. Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention. N Engl J Med 2009;360: 213-24
· Ellis SG (ed) Redefining the Art and Science of Coronary Stenting. N Engl J Med 2009;360: 292-4