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Cited by 34Cardiac Imaging and DiagnosticsCoronary Interventions and DiagnosticsFatty Acid Research and Health

Benefit of icosapent ethyl on coronary physiology assessed by computed tomography angiography fractional flow reserve: EVAPORATE-FFRCT

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Rabbat, Mark G, Lakshmanan, Suvasini, Benjamin, Mina M, Doros, Gheorghe, Kinninger, April, Budoff, Matthew J, Bhatt, Deepak L·2023·European Heart Journal - Cardiovascular Imaging
DOI 10.1093/ehjci/jead063PMC PMC10284047
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Abstract

AIMS: Icosapent ethyl (IPE) significantly reduced ischaemic events in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides in REDUCE-IT, including large reductions in myocardial infarction and elective, urgent, and emergent coronary revascularization. However, the mechanisms driving this clinical benefit are not fully known. The EVAPORATE trial demonstrated that IPE significantly reduced plaque burden. No study to date has assessed the impact of IPE on coronary physiology. Fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) data sets (FFRCT) applies computational fluid dynamics to calculate FFR values in epicardial coronary arteries. Our objective was to assess the impact of IPE on coronary physiology assessed by FFRCT using imaging data from EVAPORATE. METHODS AND RESULTS: A total of 47 patients and of 507 coronary lesions at baseline, 9 months, and 18 months with coronary CTA and FFRCT were studied in a blinded core lab. The pre-specified primary endpoint was the FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient using IPE compared with placebo. The pre-specified secondary endpoint was the change in translesional FFRCT (ΔFFRCT) across the most severe (minimum 30% diameter stenosis) coronary lesion per vessel. Baseline FFRCT was similar for IPE compared with placebo (0.83 ± 0.08 vs. 0.84 ± 0.08, P = 0.55). There was significant improvement in the primary endpoint, as IPE improved mean distal segment FFRCT at 9- and 18-month follow-up compared with placebo (0.01 ± 0.05 vs. -0.05 ± 0.09, P = 0.02, and -0.01 ± 0.09 vs. -0.09 ± 0.12, P = 0.03, respectively). ΔFFRCT in 140 coronary lesions was improved, although not statistically significant, with IPE compared with placebo (-0.06 ± 0.08 vs. -0.09 ± 0.1, P = 0.054). CONCLUSION: Icosapent ethyl demonstrated significant benefits in coronary physiology compared with placebo. This early and sustained improvement in FFRCT at 9- and 18-month follow-up provides mechanistic insight into the clinical benefit observed in the REDUCE-IT trial. Furthermore, this is the first assessment of FFRCT to determine drug effect.

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  • Icosapent ethyl confers cardiovascular benefit not just by altering plaque composition but also by improving functional coronary hemodynamics.

    “This provides additional mechanistic insight into how icosapent ethyl confers cardiovascular benefit—not just altering plaque composition, but also improving functional coronary hemodynamics [37].”

    From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [37]

    The Discussion reports improved coronary physiology with icosapent ethyl versus placebo and says the FFRCT findings provide mechanistic insight into cardiovascular benefits observed in REDUCE-IT. The Introduction and Discussion describe reduced plaque burden, but do not establish the more specific claim that this treatment altered plaque composition. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • In an analysis of EVAPORATE imaging data, icosapent ethyl improved coronary physiology via FFR-CT measurements, with early and sustained enhancement of distal segment FFR-CT at both 9- and 18-month follow-ups compared with placebo.

    “Moreover, in a landmark analysis of EVAPORATE imaging data, icosapent ethyl was the first pharmacologic agent shown to improve coronary physiology via FFR-CT measurements—an early and sustained enhancement of distal segment FFR-CT at both 9- and 18-month follow-ups compared with placebo.”

    From Targeting Triglycerides in Cardiovascular Disease Prevention: Evidence, Mechanisms, and Emerging Therapies (2026) · cites this paper as [37]

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Research works printed but not linked: 23

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Authors
Rabbat, M. G., Lakshmanan, S., Benjamin, M. M., Doros, G., Kinninger, A., Budoff, M. J., & Bhatt, D. L.
Affiliations
  • Loyola University Medical Center (US)
  • The Lundquist Institute (US)
  • Boston University (US)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Bhatt, Deepak L
ORCID
Venue
European Heart Journal - Cardiovascular Imaging
Publisher
Oxford University Press (OUP)
Published
2023-04-22
Volume
24
Issue
7
Pages
866-873
ISSN
  • 2047-2404 (ISSN-L)
  • 2047-2412
DOI
10.1093/ehjci/jead063
PMC
PMC10284047
OpenAlex
W4366602132
Cited by
34
References
4
Citations by year
2026: 9 · 2025: 11 · 2024: 8 · 2023: 6
FWCI
5.63
Type
journal article
Language
en
Open access
Licence
Locations
  • European Heart Journal - Cardiovascular Imaging (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Amgen
  • Bristol-Myers Squibb
  • AstraZeneca
  • Sanofi
  • Brigham and Women's Hospital
  • CSL Behring
  • Boston Scientific Corporation
  • Amarin Corporation
  • Belvoir Media Group
  • National Institutes of Health
  • Amarin Pharma
  • Duke Clinical Research Institute
  • Daiichi Sankyo Europe
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
  • Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
icosapent ethyl, omega-3 fatty acids, coronary physiology, fractional flow reserve, coronary artery stenosis, coronary artery disease, triglyceride-lowering therapy, coronary plaque burden, REDUCE-IT trial, statin-treated patients, atherosclerosis, diabetes mellitus, myocardial infarction, coronary revascularization
MeSH terms
Computed Tomography Angiography, Coronary Artery Disease, Coronary Vessels, Humans, Predictive Value of Tests, Severity of Illness Index, Eicosapentaenoic Acid, Coronary Angiography, Coronary Stenosis, Fractional Flow Reserve, Myocardial

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