Key result
Icosapent ethyl improves distal FFRCT by ~0.08 vs placebo at 18 months.
Why the study?
Although icosapent ethyl reduced ischaemic events in REDUCE-IT and plaque burden in EVAPORATE, its impact on coronary physiology had not been evaluated.
Does icosapent ethyl improve coronary physiology assessed by FFRCT in statin-treated patients with coronary artery disease and elevated triglycerides?
RCT (n=47)
Double-blind
1:1
Yes
Does icosapent ethyl improve coronary physiology assessed by FFRCT in statin-treated patients with coronary artery disease and elevated triglycerides?
Mean Difference: 0.08 (95% CI 0.01–0.15)
Absolute Event Rate: -0.01% vs -0.09%
p-value: p=0.03
Icosapent ethyl improves non-invasive coronary physiology (FFRCT) compared with placebo, offering a potential mechanistic explanation for the reduced ischemic events observed in the REDUCE-IT trial.
Icosapent ethyl improves coronary physiology on FFRCT in statin-treated patients; extends REDUCE-IT with mechanistic evidence for ischemic benefit.
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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Rabbat et al. (2023) conducted an RCT in Coronary artery disease with elevated triglycerides (n=47). Icosapent ethyl vs. Placebo was evaluated on Change in FFRCT value in the distal coronary segment from baseline to 18-month follow-up in the most diseased vessel per patient (MD 0.08, 95% CI 0.01-0.15, p=0.03). Icosapent ethyl significantly improved distal segment FFRCT by a mean difference of 0.08 (95% CI 0.01-0.15, p=0.03) at 18-month follow-up compared to placebo in statin-treated patients.
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