Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularization - DEFINE-FLAIR

Oct 22, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD,MPH,FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC; Kim A. Eagle, MD, MACC
Trial Sponsor:
Philips Volcano
Date Presented:
03/10/2018
Date Published:
10/16/2024
Date Updated:
10/22/2024
Original Posted Date:
03/18/2017
References

Contribution To Literature:

Highlighted text has been updated as of October 22, 2024.

The DEFINE-FLAIR trial showed that iFR was noninferior to FFR at preventing adverse cardiac events.

Description:

The goal of the trial was to evaluate if functional lesion assessment by instantaneous wave-free ratio (iFR) would be noninferior to fractional flow reserve (FFR) among patients with stable angina or acute coronary syndromes.

Study Design

  • Randomized
  • Parallel

Patients undergoing functional assessment of an indeterminant coronary lesion were randomized to iFR (n =1,242) versus FFR (n =1,250). Revascularization was recommended if the iFR value was ≤0.89 or the FFR value was ≤8.0.

  • Total number of enrollees: 2492
  • Duration of follow-up: 12 months
  • Mean patient age: 66 years
  • Percentage female: 23%
  • Percentage with diabetes: 30%

Inclusion criteria:

  • Patients with stable angina or acute coronary syndrome (unstable angina or non-ST-segment elevation myocardial infarction [STEMI])
  • Indeterminant coronary stenosis 40-70% (nonculprit vessel in acute coronary syndrome patients)

Other salient features/characteristics:

  • Radial access: 72%
  • Mean iFR: 0.91
  • Mean FFR: 0.83
  • Mean number of vessels evaluated: 1.51 with iFR vs. 1.55 with FFR (p = 0.42)
  • Functionally significant lesions: 28.6% with iFR vs. 34.6% with FFR (p = 0.004)
  • Mean number of stents: 0.66 with iFR vs. 0.72 with FFR (p = 0.09)

Principal Findings:

The primary outcome, incidence of all-cause death, MI, or unplanned revascularization at 12 months, occurred in 6.8% of the iFR group vs. 7.0% of the FFR group (p < 0.001 for noninferiority). The results were the same among tested subgroups.

Secondary outcomes:

  • Death: 1.9% for iFR vs. 1.1% for FFR
  • MI: 2.7% for iFR vs. 2.4% for FFR
  • Unplanned revascularization: 4.0% for iFR vs. 5.3% for FFR
  • Patient-reported adverse procedural symptoms: 3.1% with iFR vs. 30.8% with FFR

Cost-effectiveness: Total costs were estimated at $7,442 with iFR vs. $8,243 with FFR (p = 0.021).

Long-term outcomes:

  • All-cause death, MI, or unplanned revascularization at 5 years: 21.0% of the iFR group vs. 18.4% of the FFR group (p = 0.06)
  • All-cause mortality: 9.0% in the iFR group vs. 6.2% in the FFR group (p = 0.01)
  • Cardiovascular mortality: 4.7% in the iFR group vs. 2.6% in the FFR group (p = 0.004)
  • MI: 6.3% in the iFR group vs. 6.2% in the FFR group (p = 0.94)
  • Unplanned revascularization: 11.9% in the iFR group vs. 12.2% in the FFR group (p = 0.87)

Interpretation:

Among patients undergoing functional determination of an indeterminant coronary stenosis for stable or unstable coronary disease, iFR was noninferior to FFR. The threshold to revascularize was ≤0.89 for iFR and ≤0.80 for FFR. Adverse cardiac events were similar between study groups. There were less patient-reported adverse procedure symptoms in the iFR group. iFR was cost-effective compared with FFR. The preferential use of iFR alone (not a hybrid iFR/FFR approach) over FFR for assessment of indeterminant lesions can be considered for assessment of myocardial ischemia. The increased incidence of long-term all-cause and cardiovascular mortality in the iFR group versus the FFR group is potentially concerning; however, the mechanism for this is unclear since there was no difference in MI or unplanned revascularization.

References:

Escaned J, Travieso A, Dehbi HM, et al. Coronary Revascularization Guided With Fractional Flow Reserve or Instantaneous Wave-Free Ratio: A 5-Year Follow-Up of the DEFINE FLAIR Randomized Clinical Trial. JAMA Cardiol 2024;Oct 16:[Epublished].

Editorial Comment: Fonarow GC, Kirtane AJ, Yancy CW, et al. Parsing Signal vs Noise—Secondary Analyses of RCTs. JAMA Cardiol 2024;Oct 16:[Epublished].

Presented by Dr. Manesh Patel at the American College of Cardiology Annual Scientific Session (ACC 2018), Orlando, FL, March 10, 2018.

Davies JE, Sen S, Dehbi HM, et al. Use of the Instantaneous Wave-free Ratio or Fractional Flow Reserve in PCI. N Engl J Med 2017;376:1824-34.

Editorial: Bhatt DL. Assessment of Stable Coronary Lesions. N Engl J Med 2017;376:1879-81.

Presented by Dr. Justin E. Davies at the American College of Cardiology Annual Scientific Session (ACC 2017), Washington, DC, March 18, 2017.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Interventions and Imaging, Angiography, Nuclear Imaging

Keywords: ACC18, ACC17, ACC Annual Scientific Session, Angiography, Coronary Stenosis, Fractional Flow Reserve, Myocardial, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization


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