Angiography-derived fractional flow reserve versus intravascular ultrasound to guide percutaneous coronary intervention in patients with coronary artery disease (FLAVOUR II): a multicentre, randomised, non-inferiority trial

Abstract

Background: Revascularisation decisions based on angiography-derived fractional flow reserve (FFR) or optimisation of stent implantation with intravascular ultrasound yield superior clinical outcomes compared with percutaneous coronary intervention (PCI) guided by angiography alone. However, the differences in outcomes when a single approach is used for both purposes remain unclear. We aimed to assess the non-inferiority of angiography-derived FFR versus intravascular ultrasound guidance in terms of clinical outcomes at 12 months in patients with angiographically significant stenosis.

Methods: This investigator-initiated, open-label, multicentre, randomised, non-inferiority trial, which was done in 22 centres in China, enrolled patients aged 18 years or older with suspected ischaemic heart disease and with at least 50% stenosis in epicardial coronary arteries measuring at least 2·5 mm by visual estimation on coronary angiography. Patients were randomly assigned (1:1) to undergo PCI guided by either angiography-derived FFR or intravascular ultrasound, including revascularisation decisions and optimisation of the stent implantations based on prespecified PCI criteria and optimal PCI goals. Use of both modalities simultaneously was not permitted. Randomisation as performed using a web-based program and stratified based on the trial centre and the presence or absence of diabetes. The primary outcome was a composite of death, myocardial infarction, or revascularisation at 12 months in the intention-to-treat population, and the non-inferiority margin was 2·5 percentage points. This trial is registered with ClinicalTrials.gov, NCT04397211; long-term follow-up is ongoing.

Findings: Between May 29, 2020, and Sept 20, 2023, 1872 patients were enrolled. After 33 patients withdrew, 923 patients were randomly assigned to the angiography-derived FFR group and 916 to the intravascular ultrasound group. Median age of the study population was 66·0 years (IQR 58·0-72·0), and 1248 (67·9%) patients were male and 591 (32·1%) were female. Revascularisation was performed in 688 (69·5%) of 990 target vessels in the angiography-derived FFR group and 797 (81·0%) of 984 target vessels in the intravascular ultrasound group. At a median follow-up of 12 months (IQR 12-12), the primary outcome event occurred in 56 patients in the angiography-derived FFR group and 54 patients in the intravascular ultrasound group (6·3% vs 6·0%, absolute difference 0·2 percentage points [upper boundary of one-sided 97·5% CI 2·4], p_{non-inferiority}=0·022; hazard ratio 1·04 [95% CI 0·71 to 1·51]). Mortality did not differ between the two groups (1·8% in the angiography-derived FFR group vs 1·3% in the intravascular ultrasound group, absolute difference 0·4 percentage points [95% CI -0·7 to 1·6]; hazard ratio 1·34 [0·63 to 2·83], p=0·45). The incidence of recurrent angina was low in both groups: 26 (2·8%) of 923 patients in the angiography-derived FFR group and 35 (3·8%) of 916 patients in the intravascular ultrasound group.

Interpretation: The angiography-derived FFR-guided comprehensive PCI strategy, encompassing revascularisation decision making and stent optimisation, was non-inferior to intravascular ultrasound guidance. This finding might have implications for future guidelines on its role and application.

Funding: National Natural Science Foundation of China, The Key R & D Projects of Zhejiang Province, and the RCT Program from The Second Affiliated Hospital of Zhejiang University School of Medicine.