15 minutes of PCI FAME?

The management of stable coronary artery disease is far from clear-cut. The relative merits of medical therapy versus intervention for prognostic benefit are by no means strictly defined and national guidelines reflect this uncertainty, with intervention on single vessel stenoses >50% a class I level C recommendation (1).

These very guidelines were updated in 2013 to reflect the paradigm shifting work of the FAME investigators in demonstrating the utility of an FFR guided approach to coronary revascularisation. The original trial demonstrated the benefit of offering revascularisation in stable coronary artery disease only to patients with coronary stenosis with a significant FFR (<0.80), irrespective of angiographic appearances (2).

However, this trial was much criticised, not least in the decision by the safety investigators to terminate the trial early. Crucially there was no difference in the rate of death or MI between the two strategies of PCI or optimal medical therapy in the patients with a significant FFR value, that is patients with stenoses that could induce myocardial ischaemia. The difference in end point was driven by the need for urgent revascularisation in patients who had been managed with optimal medical therapy alone. This was in the context of patients’ being aware of their coronary anatomy and also the decision not to proceed with PCI. The argument from the naysayers was that this might drive the over-anxious patient to earlier re-presentation with cardiac symptoms and the equally anxious physician to earlier repeat imaging and intervention.

The investigators have now completed their pre-specified 2 year analysis of outcomes (3). In total 1220 patients were enrolled in the original study. 888 had at least one stenosis with an FFR of 0.80 or less in a large epicardial artery. 447 of these were randomised to PCI plus OMT, 441 were randomised to OMT alone. The 332 patients with an FFR >0.80 were followed up in a registry.

Now at 2 years, the composite primary end point of death, MI or urgent revascularisation had occurred in 8.1% of the PCI group, similar rates in the registry group at 9% but a staggering 19.5% of the medical therapy alone group.

Addressing one key question in whether the between group differences were limited to differences in urgent revascularisation alone, one of the key figures in the follow up data is that after 7 days and up to 2 years, patients in the PCI group had a statistically significantly lower risk of death or MI (excluding the revascularisation figures) compared to patients in the medical therapy group (4.6% v 8%). The majority of events in the PCI group were periprocedural MIs which likely explains why the overall difference in death and MI between groups was not statistically significant.

However, the study also reaffirms what many original critics had suspected. The stark difference in the need for urgent revascularisation between the PCI and medical therapy groups (4% vs 16.3%) was largely driven by clinical features only (49%), with the remaining smaller proportions being due to ischaemic ECG changes and myocardial infarctions.

Nevertheless, the findings of this follow up study merit serious consideration. Firstly, the outcomes of the registry group reinforces what is now largely well established, that is the need for ischaemia driven intervention. Furthermore, early FFR guided PCI in patients with stable coronary artery disease shows clear symptomatic benefit, in that it reduces the need for largely symptom driven urgent revascularisation. I would suggest this is not to be taken lightly or seen as a softer end point. Anything we do as physicians should fulfil one of two equally noble aims; to make people feel better or live longer. In addition, once the perils of the immediate peri-procedural period are navigated, there is a clear trend towards prognostic benefit also. As PCI procedural safety improves, we may well see a repeat study demonstrating clear prognostic benefits of PCI in this setting. The FAME investigators will likely have their 15 minutes and more.

References

1. 2013 ESC Guidelines on the Management of Stable Coronary Artery Disease. European Heart Journal (2013); 34: 2949-3003. http://eurheartj.oxfordjournals.org/content/34/38/2949.full.pdf
2. de Bruyne B, Pijls NH, Kalesan B, Barbato E, Tonino PA, Piroth Z, Jagic N, Mobius-Winckler S, Rioufol G, Witt N, Kala P, MacCarthy P, Engstrom T,Oldroyd KG, Mavromatis K, Manoharan G, Verlee P, Frobert O, Curzen N, Johnson JB, Juni P, Fearon WF. Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease. N Eng J Med 2012;367:991–1001.
3. De Bruyne B, Fearon WF, Pijls NHJ, et al. Fractional flow reserve–guided PCI for stable coronary artery disease. N Engl J Med. Online publication ahead of print publication. DOI: 10.1056/NEJMoa1408758.