The FLAVOUR Randomized Clinical Trial: Comparison of Fractional Flow Reserve-guided and Intravascular Ultrasound-guided Percutaneous Coronary Intervention in Intermediate Coronary Artery Stenosis
Reported from ACC 2022
Daniele Giacoppo analyses the main results of the FLAVOUR trial which were presented by Bon-Kwon Koo, from Seoul National University Hospital, South Korea at the American College of Cardiology 2022.
In stable coronary artery disease, fractional flow reserve (FFR) and intravascular ultrasound (IVUS) are established diagnostic tools to guide myocardial revascularization and optimize percutaneous coronary intervention (PCI). The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) trial showed that PCI-guided FFR is associated with improved outcomes and a lower number of implanted stents compared with angiography-guided PCI. On the other hand, some randomized clinical trials, such as ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in All-Comers Coronary Lesions) and IVUS-XPL (Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions), showed that IVUS-guided PCI and stenting optimization are associated with improved outcomes compared with angiography-guided PCI.
However, the comparison between FFR and IVUS is challenging due to the different levels of information provided, functional and morphological, respectively, and there is uncertainty on the comparative influence of these techniques on long-term outcomes.
In recent years, some studies have focused on the differential prognostic value of invasive functional assessment versus intravascular imaging of coronary artery disease but the amount of evidence accrued is still insufficient for providing answers.
In the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound-Guided Intervention Strategy for Clinical Outcomes in Patients with Intermediate Stenosis) trial, 1682 patients suffering from stable coronary artery disease amenable to percutaneous coronary intervention (PCI) with a 40-70% coronary stenosis as assessed by angiography, located in a native non-left main segment of ≥ 2.50 mm, were randomized at 18 centres in China and South Korea to FFR- (n=838) or IVUS-guided (n=844) treatment.
In the FFR group, PCI was indicated for FFR ≤ 0.80, and satisfactory revascularization was considered for postprocedural FFR ≥ 0.88 or a difference < 0.05 in FFR values across the stent. In the IVUS group, PCI was indicated for minimal luminal area (MLA) ≤ 3.00 mm2 or 3.00-4.00 mm2 with plaque burden >70%, and satisfactory revascularization was considered for postprocedural MLA ≥ 5.5 mm2 and plaque burden at stent edge ≤ 55% or an in-stent MLA ≥ distal reference lumen area. Patients who did not meet the requirement for PCI underwent medical therapy.
The main objective of the FLAVOUR trial was to test the noninferiority of FFR- vs. IVUS-guided PCI in terms of a patient-oriented composite endpoint of major adverse cardiac events including all-cause death, myocardial infarction, and any revascularization at 24 months. Events were adjudicated by an independent clinical events committee. The trial was investigator-initiated and funded by Boston Scientific.
Bon-Kwon Koo, MD, PhD, of Seoul National University Hospital, South Korea presented the main results of the FLAVOUR trial at the American College of Cardiology 2022.
The mean age was 65 years, 29.4% were female, 32.9% had diabetes mellitus, and 52.0% had multivessel disease. The rate of PCI performance was significantly lower in the FFR group than in the IVUS group (44.4% vs. 65.3%, p < 0.001). Consistently, the number of stents implanted per patient in the FFR group was significantly lower than in the IVUS group (0.6 +- 0.9 vs. 0.9 +- 1.0, p < 0.001) as well as the proportion of patients discharged on dual antiplatelet therapy (58.1% vs. 71.8%).
A total of 832 patients (99.1%) assigned to FFR and 836 patients (99.3%) assigned to IVUS were available for the primary analysis. At 24-month follow-up, IVUS resulted to be noninferior to FFR in terms of all-cause death, myocardial infarction, or any revascularization (8.1% vs. 8.6%, pnoninferiority=0.015). Per-protocol analysis was consistent (8.2% vs. 8.7%, pnoninferiority=0.016). No significant difference in the primary outcome between FFR and IVUS guidance was observed in both the cohort of patients treated by PCI (FFR, n=466, and IVUS, n=293;11.9% vs. 9.9%, p=0.313) and the cohort of patients treated by medical therapy (FFR, n=372, and IVUS, n=551; 5.0% vs. 5.9%, p=0.622).
The primary endpoint between FFR and IVUS group was not influenced by significant interaction in exploratory subgroup analyses.
Each individual component of the primary endpoint resulted to be nonsignificantly different between FFR- and IVUS-guided PCI (all-cause death: 1.3% vs. 2.3%, p=0.147; myocardial infarction: 1.9% vs. 1.7%, p=0.696; 5.7% vs. 5.3%, p=0.713; repeat revascularization: 5.7% vs. 5.3%, p=0.713). Consistently no significant difference between FFR and IVUS groups was observed with respect to periprocedural (1.2% vs. 0.9%, p=0.623) and target vessel myocardial infarction (0.4% vs. 0.2%, p=0.648) as well as target vessel revascularization between FFR and IVUS guidance was nonsignificantly different (3.3% vs. 2.4%, p=0.288). Finally, assessment of patient-reported outcomes at follow-up by Seattle Angina Questionnaire did not reveal significant differences in scores between FFR and IVUS groups.
Based on the FLAVOUR trial, either invasive functional assessment by FFR or intravascular imaging by IVUS can be used to guide PCI and optimize stent implantation. However, these results refer only to stable non-left main intermediate-degree stenoses in native vessels and may not apply to more severe patterns of coronary artery disease and clinical presentations. Moreover, it is unclear whether the prognostic equivalence of FFR and IVUS can be extended to other physiological indexes (e.g., instantaneous wave-free ratio) and other invasive imaging modalities (e.g., optical coherence tomography).
In this regard, the FORZA (FFR or OCT Guidance to RevasculariZe Intermediate Coronary Stenosis Using Angioplasty) trial, including patients randomly assigned to FFR- vs. optical coherence tomography-guided PCI showed that the intravascular imaging group was associated with improved outcomes compared with the invasive functional assessment group. Finally, the amount of data disclosed does not clarify whether per-protocol application of FFR and IVUS requirements to identify significant coronary artery disease and optimize PCI was consistent across patients after core laboratory revision of index procedure data and the use of multiple definitions, based on mixed supporting evidence, to identify appropriate PCI optimization may warrant specific sensitivity analyses.
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