FLOWER-MI: FFR Shows No Benefit over Angio for Complete Revasc in Multi-vessel STEMIs
Findings say FFR-guided PCI not superior (or cost-effective) compared to angio-guided PCI, although experts warn results may not be conclusive
Fractional flow reserve (FFR)-guided complete revascularization of STEMI patients with multi-vessel disease was not superior to stenting guided by angiography alone, FLOWER-MI findings showed.
The first head-to-head study findings in the patient group showed FFR-guided percutaneous coronary intervention (PCI) did not improve 1-year endpoint outcomes of mortality, myocardial infarction (MI), or urgent revascularization compared to angio-guided PCI.
Presenting study findings at the annual American College of Cardiology Scientific Sessions (ACC 2021) held last month, principal study investigator Etienne Puymirat, MD (University of Paris; Georges Pompidou Hospital; Paris, France) also explained that FFR-guided complete revascularization was not more cost-effective than angio-guidance alone.
ˇ°The strategy of using FFR to guide stenting is not superior to the standard angiography technique to treat additional partially blocked arteries,ˇ± Puymirat said. ˇ°In addition to no [outcome] benefit, we have also shown that - based on the costs in France - the FFR-guided strategy is more expensive.ˇ±1
These findings, simultaneously published in the New England Journal of Medicine on May 162, run contrary to the previous FAME trial3 wherein FFR-guided PCI for stable multi-vessel disease patients demonstrated lower 1-year MACE incidence than angio-guided PCI (13.2% vs. 18.3%, P=0.02).
Despite the new evidence, experts cautioned against understanding results as definitive, with investigators explaining that ˇ°given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation.ˇ±
FLOWER-MI questions optimal revascularization technique in multi-vessel STEMI
Current guidelines recommend routine complete revascularization - also known as PCI for nonculprit lesions - in STEMI patients with multi-vessel disease, albeit without recommending a particular stenting technique.
The guideline recommendation for complete revascularization has been backed by studies such as COMPLETE4 trial that demonstrated complete revascularization led to fewer subsequent PCI procedures and less CVD death or MI.
Studies such as the DAMANI-3-PRIMULTI5 and COMPARE-ACUTE6 have also shown that FFR-guided complete revascularization of nonculprit arteries is superior to FFR-guided revascularization of culprit lesions only, leading to lower MACE, CV death, and MI incidence as well as fewer subsequent PCI procedures.
Therefore, although current evidence implies complete revascularization is better than PCI for culprit lesions only, questions have emerged regarding optimal PCI strategies in the STEMI subgroup, particularly regarding FFR- or angio-guided PCI.
To address the evidence gap, FLOWER-MI investigators sought to compare the two strategies for complete revascularization in multi-vessel STEMIs.
FFR-PCI ˇ®not superiorˇŻ to angio-PCI but experts caution against results being final
The randomized multicenter FLOWER-MI trial conducted in 41 centers across France included 1,171 patients with STEMI and multi-vessel disease (avg. 62 years old; 83% men) who had undergone successful PCI with 50% or more stenosis in at least one additional nonculprit lesion.
After the culprit vessel PCI, all patients were immediately randomly assigned to a second non-culprit vessel PCI guided either by FFR (n=586) or by angiography alone (n=577). The second procedure was performed within five days of the first.
Patient analysis showed those in the FFR arm had fewer stents placed for nonculprit lesions than in the angiography arm (mean stents: FFR-group 1.01 vs. angio-group 1.50).
The primary outcome at 1-year was the composite of death from any cause, nonfatal MI, or unplanned hospitalization leading to urgent revascularization.
Follow-up over 12 months showed the primary outcome occurred in 5.5% of the FFR-guided group and 4.2% of the angio-guided group, failing to demonstrate superiority (HR 1.32, 95% CI, 0.78-2.23, P=0.31).
The study, therefore, failed to meet its primary endpoint while other composite outcomes also failed to prove the benefit of FFR-guidance over angio-guidance.FFR-guided vs. angio-guided revascularization:
- Primary outcome: 5.5% vs. 4.2% (HR 1.32, 95% CI, 0.78-2.23, P=0.31)
- Death: 1.5% vs. 1.7% (HR 0.89, 0.36-2.20)
- Nonfatal myocardial infarction 3.1% vs. 1.7% (HR 1.77, 0.82-3.84)
- Unplanned hospitalization requiring urgent revasc: 2.6% vs. 1.9% (HR 1.34, 0.62-2.92)
Analysis of the secondary endpoint concerning cost-efficacy indicated FFR-guided PCI cost a median of 500 euros ($600) more than angio-guided PCI (˘ć8,832 vs. ˘ć8,322; P<0.01).
Puymirat, however, pointed out that MACE incidence in both groups was considerably lower than researchers expected.
Given the wide confidence intervals for the estimate of effect, the findings do not allow for a conclusive interpretation.
Wide confidence intervals also required caution in interpreting findings as conclusive (95% CI, 0.78-2.23), he added.
ˇ°These patients were at high cardiovascular risk due to multi-vessel disease,ˇ± Puymirat said. ˇ°Using data from previous trials and registries in this population, we estimated that about 15% of patients would have an adverse event within one year, but in our study, the rate was 5% at 1-year.ˇ±
William Fearon, MD (Stanford University Medical Center, USA) discussed the study findings as an ACC panel discussant, saying: ˇ°Only about one-third of FFR-guided patients (or about 200 patients) did not receive nonculprit PCI and therefore we could only expect a difference in outcomes in only this small group versus the angio-guided group.ˇ±
Commenting on the study for SummitMD, Jung-min Ahn, MD (Asan Medical Center, Seoul, South Korea) argued that, ˇ°While FLOWER-MI can be interpreted as a negative trial, it still provides an important message – namely that FFR can defer up to a third of non-culprit lesions noted at the time of STEMI without increasing incidence of death, MI, or urgent revascularization. FFR-guidance could also defer unnecessary PCIs, and therefore result in cost-savings.ˇ±
The FLOWER-MI study - funded by the French Ministry of Health and Abbott - will continue to follow patients for 2 more years, investigators said.