FFR Disappoints as Guide for PCI on Non-Culprit Lesions in STEMI

Hemodynamic assessment did not improve guidance for complete revascularization in multivessel stenting for patients with ST-segment elevation MI (STEMI), according to the FLOWER-MI trial.

Fractional flow reserve (FFR) was no better than angiography at guiding percutaneous coronary intervention (PCI) on nonculprit lesions in terms of 1-year clinical outcomes among more than 1,000 study participants, reported Etienne Puymirat, of the European Hospital of Georges Pompidou in Paris.

By then, the combined rate of all-cause mortality, MI, or unplanned hospitalization leading to urgent revascularization was similar between patients randomized to FFR or angiographic guidance (5.5% vs 4.2%, HR 1.32, 95% CI 0.78-2.23). There were no differences in individual endpoint components either, Puymirat said at the American College of Cardiology (ACC) virtual meeting. FLOWER-MI results were simultaneously published in the New England Journal of Medicine.

“However, given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation,” Puymirat’s group warned. A major limitation of the trial was the low number of clinical events resulting in the main analysis being underpowered.

According to William Fearon, MD, of Stanford University in California, it could be expected that the two groups would have no difference in outcomes given that every patient received primary PCI and the majority of each group underwent subsequent PCI for a nonculprit vessel. He was not involved with FLOWER-MI.

Yet the numerically higher event rate after FFR guidance was a surprise, according to Roxana Mehran, MD, of Mount Sinai Hospital in New York City, who was also not involved in the study.

Ultimately, the lack of statistical difference in outcomes between groups “begs the question of whether physiology-guided PCI is enough in preventing subsequent events, especially in borderline lesions in the setting of MI, when we know that these patients have other vulnerable plaques that may not be best detected by physiologic evaluation,” Mehran said.

“Given the inconclusive FLOWER-MI trial results, clinicians should continue performing non-culprit PCI in patients with STEMI and multivessel disease, but should do so using an angio-[guided] rather than an FFR-guided, strategy,” commented Herbert Aronow, MD, MPH, of Lifespan Cardiovascular Institute and Alpert Medical School of Brown University in Providence, Rhode Island.

FLOWER-MI was a multicenter trial that enrolled STEMI patients with multivessel disease after they had undergone successful PCI of the infarct-related artery. Participants were randomized to FFR guidance (n=586) or angiographic guidance (n=577).

The two groups shared similar baseline characteristics. Mean age was 62.2, and men accounted for over 80% of the total cohort.

Complete revascularization occurred over staged intervention around 3 days apart in over 95% of people in each study arm, suggesting that “FFR measurement that is performed at the same time as PCI of the infarct-related artery may be unrealistic under routine clinical conditions,” according to the FLOWER-MI group.

“Our results should therefore be interpreted as pertaining to patients who are undergoing staged multivessel procedures. Staged procedures expose the patient to a second procedure with its associated risks, and in some instances the second procedure proves unnecessary since no intervention will be performed,” the authors said.

Average number of stents placed per patient in nonculprit lesions was 1.01 and 1.50 among FFR and angiography groups, respectively.

This was a surprising difference “suggesting that most nonculprit lesions were severe and not intermediate, where measurement of FFR might have more of a benefit,” Fearon said.

FFR guidance had been previously shown to reduce major adverse cardiovascular events over angiography in PCI on people with stable multivessel disease in the FAME trial, study authors noted.

It is unclear why the findings of FAME differ from FLOWER-MI.

Notably, PCI was performed in 66.2% of FFR group and 97.1% of the angiography group in FLOWER-MI, reflecting stricter criteria for performing PCI with FFR. Operators had been told to measure FFR in all lesions judged to have stenosis at least 50% on visual estimation; FFR 0.80 or less was considered clinically important.

“In our trial, the event-rate curves for the primary outcome diverged after 6 months. Although this divergence may constitute an artifact in view of the limited number of events, it is also possible that some lesions that had been left untreated in the FFR-guided group worsened during follow-up, which led to the occurrence of clinical events,” Puymirat’s group suggested.

Aronow cited DANAMI-3 and Compare-Acute as trials that had supported FFR guidance in complete revascularization.

Future comparisons of FFR and angiography in complete revascularization for STEMI are not likely to happen, Puymirat and colleagues suggested.

“Given the low incidence of events observed, more than 8,000 patients would be needed to show a 15% lower relative risk of the composite outcome; this reduction would correspond to a lower absolute risk of 0.6 percentage points for the FFR-guided strategy, a difference of doubtful clinical significance,” they wrote.