The role of percutaneous coronary intervention (PCI) for the treatment of patients presenting with acute coronary syndromes has been firmly established, as it confers a survival benefit.1,2 Nonetheless, a substantial number of PCI worldwide are not performed in an acute setting; instead the technique is used for patients with stable coronary artery disease. According to data from the CathPCI Registry,3 29.6% of PCI performed in the USA were for patients with stable angina, atypical symptoms, or those that had no symptoms. The efficacy of the procedure in the nonacute context has been addressed by a number of randomised controlled trials, registries and meta-analyses, with conflicting results.4,5 A key point for the interpretation of these results is that the decision to perform PCI was based on visual (anatomical) assessment of the lesions, thus not taking into account their physiological impact.
The Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 (FAME 2) trial sought to address this issue and compared the outcomes of PCI plus medical therapy to medical therapy alone in patients with stable coronary artery disease that had functionally significant stenoses. All lesions that were angiographically significant were assessed by fractional flow reserve (FFR). Only patients that had at least one lesion with an FFR value ≤0.80 were subsequently randomised to receive either PCI with second-generation drug-eluting stents (DES) plus medical therapy or medical therapy alone. The primary endpoint was a composite of death, myocardial infarction, or unplanned hospitalisation that led to urgent revascularisation. Patients were followed-up for 5 years and had their angina status assessed at each time point.
Enrolment was stopped prematurely, due to a significant difference in the primary endpoint in favour of the PCI group. Of the 1,220 enrolled patients, 888 had at least one functionally significant stenosis (FFR≤0.80) and were randomised to either the PCI plus medical therapy group (n=447) or the medical therapy alone group (n=441). The outcomes at 1, 2, and 3 years have been previously reported, and point to a beneficial effect of PCI for the primary endpoint (driven by a significant reduction of urgent revascularisations), a numerically lower rate of death or myocardial infarction and significant reduction in angina with comparable cost to medical therapy alone.6-8
The final 5-year results of the trial, which were recently published, confirm and lend further support to the long-term efficacy of an FFR-guided PCI strategy for patients with stable coronary artery disease.9 Patients treated with PCI had a significantly lower event rate for the primary endpoint as compared to patients treated with medical therapy alone (13.9% versus 27.0%; hazard ratio: 0.46; 95% confidence interval: 0.34–0.63) and their event rate was comparable to patients that did not have any functionally significant lesion (13.9% versus 15.7%; hazard ratio: 0.88; 95% confidence interval: 0.55–1.39). While urgent revascularisation remained the main driver of the lower event rate in the PCI group, a strong signal towards a lower rate of myocardial infarctions emerged (8.1% versus 12.0%; hazard ratio: 0.66; 95% confidence interval: 0.43–1.00). More than half (51%) of the patients randomised to receive medical therapy alone eventually crossed over to the PCI group and this may explain why relief from angina was comparable between the two groups at 5 years.
In summary, the 5-year results of the FAME 2 trial confirm the role of FFR for selecting patients that will benefit from PCI. Only patients with functionally significant lesions derive long-term benefits after stenting regarding relief from angina and urgent revascularisation. Importantly, and despite the high cross-over rate that may have diluted the results, there is now evidence that an FFR-guided PCI strategy has a beneficial effect on a hard outcome such as myocardial infarction.