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Beneficial Effects of Icosapent Ethyl on Coronary Physiology as Assessed by FFRCT
TAKE-HOME MESSAGE
- In this post hoc analysis of the EVAPORATE trial involving 47 patients and 507 coronary lesions, treatment with icosapent ethyl was associated with a significant improvement in FFRCT imaging results in the most diseased vessel per patient at both 9 and 18 months compared with mineral oil placebo.
- These findings demonstrate the beneficial effect of icosapent ethyl on epicardial coronary physiology and provide mechanistic insights into the clinical benefits observed in the REDUCE-IT trial.
abstract
This abstract is available on the publisher's site.
Access this abstract nowAIMS
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Benefit of icosapent ethyl on coronary physiology assessed by computed tomography angiography fractional flow reserve: EVAPORATE-FFRCT
Eur Heart J Cardiovasc Imaging 2023 Apr 21;[EPub Ahead of Print], MG Rabbat, S Lakshmanan, MM Benjamin, G Doros, A Kinninger, MJ Budoff, DL BhattFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The EVAPORATE trial has shown that icosapent ethyl, a highly purified prescription form of the omega-3 fatty acid eicosapentaenoic acid (EPA), significantly reduced coronary plaque progression compared with placebo. The present analysis examined fractional flow reserve on coronary CT angiography (FFRCT) at baseline and during follow-up as a measurement of coronary blood flow. There was a significant improvement in FFRCT with icosapent ethyl versus placebo. This effect may partly explain the significant reduction in the need for PCI and CABG as noted in the REDUCE-IT trial. Beyond providing further mechanistic insights into EPA, these data are the first evidence of a drug effect on FFRCT. While FFRCT already has an important guideline indication for use in the evaluation of chest pain, it will likely also have a role in the investigation of novel as well as established cardiovascular drugs.