In the FLOWER-MI study, Puymirat et al investigated the use of FFR compared to angiography-guided nonculprit vessel PCI. A total of 1163 patients presenting with STEMI and multivessel disease who had undergone successful PCI to the culprit vessel, were randomized to either FFR guidance or angiography guidance among 41 centers in France. The authors found that after 1 year, there was no difference in composite endpoint of death, nonfatal MI or unplanned hospitalization leading to urgent revascularization in the FFR-guided group compared to angiography-guided group (5.5% vs 4.2%, HR, 1.32; 95% CI, 0.678-2.23; P = .31). There was also no difference in individual components of primary outcomes or secondary outcomes such as rate of stent thrombosis, any revascularization, or hospitalization.
There are a few interesting points to consider in this study. Ever since the Fractional Flow Reserve vs Angiography for Multivessel Evaluation (FAME) trial reported the lower incidence of major adverse events in routine FFR measurement during PCI compared to angiography-guided PCI, physiological assessment has become the gold standard for treatment of stable ischemic heart disease.7 However, the results of the current FLOWER-MI trial were not consistent with the FAME trial and there are few possible reasons to consider.
First, the use of FFR in the setting of STEMI is less validated compared to stable ischemic heart disease.8 Microvascular dysfunction during the acute phase can affect the FFR reading and the lesion severity can be underestimated.8 Second, the rate of composite endpoint was much lower in this study compared to FAME despite using the same composite endpoint of death, nonfatal MI, and unplanned hospitalization leading to urgent revascularization. At 1 year, the incidence of primary outcome was 13.5% in the FFR-guided group compared to 18.6% in the angiography-guided group in the FAME study compared to 5.5% and 4.2% in the FLOWER-MI study, despite having a sicker population presenting with STEMI. This is likely due to improvement in the PCI techniques such as radial approach, imaging guidance, and advancement in medical therapy such as use of more potent antiplatelet therapy. With lower incidence of primary outcome, larger number of patients are needed to detect the difference in the composite outcome. Finally, the operators’ visual assessment may have been calibrated to the physiologic assessment as the operators are routinely using FFR assessment which may have diminished the benefit of FFR guidance seen in the early FAME study.
Another interesting finding from this study was that although the study protocol encouraged the operators to perform the nonculprit PCI in the same setting, only 4% had nonculprit PCI in the same setting and 96% of the patients underwent a staged PCI. The advantage of performing the nonculprit PCI on the same setting is to have 1 fewer procedure for the patient. On the other hand, the disadvantage of this approach includes prolongation of the index procedure, theoretically higher risk of complication during the acute phase and vasospasm leading to overestimation of the lesion severity. A recent analysis from the COMPLETE study did not show any difference when comparing staged PCI during the index hospitalization vs after discharge.9 The optimal timing of the staged PCI needs to be investigated in future studies.
A limitation of this study is the lower than expected incidence of clinical events decreasing the statistical power of the study. However, there was no signal that FFR-guided PCI is better compared to the angiography-guided group. In fact, the curve started to diverge at 6 months favoring the angiography-guided group. In addition, there was no core-lab analysis for completeness of revascularization.
Applications for Clinical Practice
In patients presenting with hemodynamically stable STEMI for undergoing nonculprit vessel PCI, both FFR-guided or angiography-guided strategies can be considered.
Financial disclosures: None.