Is the Improvement in Fractional Flow Reserve After Percutaneous Coronary Intervention (ΔFFR) Associated With Clinical Outcome and Symptomatic Relief?

In an analysis of two randomized clinical trials published in JAMA cardiology, Fournier et al. reported that the larger the improvement in FFR, the larger the symptomatic relief and the lower the event rate. This was suggestive of the fact that measuring FFR before and after PCI could provide clinically useful information.

Prior to this study, it was unclear whether the improvement in myocardial perfusion provided by percutaneous coronary intervention (PCI) was associated with symptomatic relief or improved outcomes. After percutaneous coronary intervention (PCI), fractional flow reserve (FFR) was generally smaller than 1.0. Two recent studies had supported the concept that the higher the post-PCI FFR value is, the better the patient’s condition is. Yet, the potential of any post-PCI FFR value to prognosticate an outcome remained low. While a final hemodynamic result could be identical, the improvement in FFR value could be different and bear a different meaning for the patient. The authors hypothesized that the improvement in FFR (ΔFFR) reflected a decrease in ischemic burden, determined symptomatic relief, and bore prognostic value. Fournier and her colleagues aimed to investigate the prognostic value of the improvement in fractional flow reserve (FFR) after PCI (ΔFFR) on patients’ symptoms and 2-year outcomes.

The study was designed as a post hoc analysis of data from patients undergoing FFR-guided PCI in the randomized clinical trials Fractional Flow Reserve vs Angiography for Multivessel Evaluation FAME 1  and FAME 2, with the inclusion of 2 years of follow-up data. The FAME 1 trial included patients with multivessel coronary artery disease from 20 medical centers in Europe and the United States. The FAME 2 trial included patients with stable coronary artery disease involving up to 3 vessels from 28 sites in Europe and North America. Lesions from the group in the FAME 1 trial from whom FFR was measured and the group in the FAME 2 trial who received FFR-guided PCI plus medical therapy were analyzed. Data analysis occurred from May 2017 to May 2018.  The major outcomes that were measured included vessel-oriented clinical events at 2 years, a composite of cardiac death, target vessel-associated myocardial infarction, and target vessel revascularization. A total of 639 patients were included in the analysis from whom pre-PCI and post-PCI FFR values were available. Of their 837 lesions, 277 were classified into the lowest tertile (ΔFFR  ≤0.18), 282 into the middle tertile (0.19  ≤ΔFFR  ≤0.31), and 278 into the highest tertile (ΔFFR>0.31). Vessel-oriented clinical events were significantly more frequent in the lowest tertile (n = 25 of 277 [9.1%]) compared with the highest tertile (n = 13 of 278 [4.7%]; hazard ratio, 2.01 [95%CI, 1.03-3.92]; P = .04). In addition, a significant association was observed between ΔFFR and symptomatic relief (odds ratio, 1.33 [95%CI, 1.02-1.74]; P = .02).

The investigators concluded that the incidence of vessel-oriented clinical events was significantly greater among patients in the lowest tertile of ΔFFR compared with those in the uppermost tertile, and a significant association was observed between ΔFFR and symptomatic relief. These findings suggested that patients in whom only a modest improvement in FFR could be obtained by percutaneous coronary intervention were at higher risk of events and were more likely to have more persistent complaints. Primary investigator Dr. Stephane Fournier commented, “This study confirms and quantifies our clinical intuition, namely, that the larger the ΔFFR, the larger the symptomatic improvement. These data extend the findings of the Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina (ORBITA) trial, which showed a physiology-stratified effect of PCI on symptomatic relief, to a broader patient population. These data also indicate that the larger the ΔFFR, the lower the rate of VOCEs at 2 years after PCI. Per this analysis, these outcomes are more closely associated with ΔFFR than both pre-PCI FFR and post-PCI FFR values.” However, certain limitations needed to be accounted for. First, this was not a prespecified post hoc analysis of the randomized clinical trial data. Second, failing to perform a final FFR assessment could introduce a bias. It could be speculated that, at the end of a difficult procedure, the final FFR value was less often measured than after a swift procedure with excellent angiographic results. Third, pullback with pressure wires was not recorded. Accordingly, it was not possible to distinguish between an in-segment, residual gradient or a diffusely distributed gradient. Finally, in the FAME 2 protocol, operators were allowed to infer an FFR value of 0.50 for a small number of lesions through which the operator did not feel confident advancing a pressure wire. Excluding these lesions did not change the conclusions of the present analysis. In addition, in this study, the pre-PCI FFR values did not influence the significant association between ΔFFR and VOCEs.