Fractional Flow Reserve vs. Angiography in Guiding Management to Optimize Outcomes in Non-ST-segment Elevation Myocardial Infarction

The British Heart Foundation Famous-NSTEMI Randomized Trial

Jamie Layland; Keith G. Oldroyd; Nick Curzen; Arvind Sood; Kanarath Balachandran; Raj Das; Shahid Junejo; Nadeem Ahmed; Matthew M.Y. Lee; Aadil Shaukat; Anna O'Donnell; Julian Nam; Andrew Briggs; Robert Henderson; Alex McConnachie; Colin Berry


Eur Heart J. 2015;36(2):100-111. 

In This Article

Abstract and Introduction


Aim We assessed the management and outcomes of non-ST segment elevation myocardial infarction (NSTEMI) patients randomly assigned to fractional flow reserve (FFR)-guided management or angiography-guided standard care.

Methods and results We conducted a prospective, multicentre, parallel group, 1 : 1 randomized, controlled trial in 350 NSTEMI patients with ≥1 coronary stenosis ≥30% of the lumen diameter assessed visually (threshold for FFR measurement) (NCT01764334). Enrolment took place in six UK hospitals from October 2011 to May 2013. Fractional flow reserve was disclosed to the operator in the FFR-guided group (n = 176). Fractional flow reserve was measured but not disclosed in the angiography-guided group (n = 174). Fractional flow reserve ≤0.80 was an indication for revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). The median (IQR) time from the index episode of myocardial ischaemia to angiography was 3 (2, 5) days. For the primary outcome, the proportion of patients treated initially by medical therapy was higher in the FFR-guided group than in the angiography-guided group [40 (22.7%) vs. 23 (13.2%), difference 95% (95% CI: 1.4%, 17.7%), P = 0.022]. Fractional flow reserve disclosure resulted in a change in treatment between medical therapy, PCI or CABG in 38 (21.6%) patients. At 12 months, revascularization remained lower in the FFR-guided group [79.0 vs. 86.8%, difference 7.8% (−0.2%, 15.8%), P = 0.054]. There were no statistically significant differences in health outcomes and quality of life between the groups.

Conclusion In NSTEMI patients, angiography-guided management was associated with higher rates of coronary revascularization compared with FFR-guided management. A larger trial is necessary to assess health outcomes and cost-effectiveness.


Non-ST segment elevation myocardial infarction (NSTEMI) is the commonest form of acute coronary syndrome (ACS), the most common indication for invasive coronary angiography, and a leading global cause of premature morbidity and mortality.[1] Coronary angiography in ACS patients can detect obstructive coronary artery disease and identify patients who may benefit from coronary revascularization.[1–3] Usual care is based on visual interpretation of coronary disease severity and management decisions include medical therapy, percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Visual assessment of lesion severity with coronary angiography may be inaccurate resulting in over- or underestimation of the physiological significance of the lesion.[4,5] Hence judgements made by cardiologists in every day practice are subjective, potentially leading to misdiagnosis and incorrect treatment decisions.[4–6]

An alternative approach involves the measurement of the myocardial fractional flow reserve (FFR) using a pressure-sensitive coronary guidewire. Fractional flow reserve assesses the physiological significance of a coronary stenosis and is expressed as the ratio of maximal blood flow in a stenotic artery to maximal flow in an unobstructed artery.[7] Recent studies (DEFER,[8] FAME,[9] FAME-2,[10] and RIPCORD[11]) have evaluated the value of FFR to guide treatment decisions. An FFR ≤0.80 is an evidence-based physiological threshold that correlates with the presence of inducible ischaemia on non-invasive testing.[7] Fractional flow reserve values >0.80 indicate that patients can be managed safely with medical therapy without the need for coronary revascularization.

Fractional flow reserve measurements require maximal coronary hyperaemia which may be less readily achieved in patients with acute coronary disease because of coronary microvascular dysfunction.[12,13] Recent clinical studies indicate that FFR in this setting may be valid[14–18] but in the absence of evidence from randomized prospective trials, a routine physiological approach for the management of patients with recent MI is not recommended in guidelines.[1–3] We hypothesized that management decisions in patients with NSTEMI undergoing coronary angiography guided by routine FFR measurement would be feasible and safe, and would provide additive clinical utility compared with standard care based on visual interpretation of the angiogram.