What is the clinical evidence from this study?

Study design: RCT. Population: Atherosclerosis or diabetes with elevated triglycerides (n=47). Intervention: Icosapent ethyl vs. Placebo. Primary outcome: FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patient (p=0.03).

April 21, 2023Open Access

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

Key Result

Icosapent ethyl significantly improved mean distal segment FFRCT at 18-month follow-up compared with placebo (-0.01 vs -0.09; P=0.03), demonstrating a benefit on coronary physiology.

Study Design

Type

RCT (n=47)

Blinding

Blinded

Structured PICO

Does icosapent ethyl improve coronary physiology assessed by FFRCT in statin-treated patients with atherosclerosis or diabetes and elevated triglycerides?

Population

47 statin-treated patients with atherosclerosis or diabetes and elevated triglycerides, evaluated with coronary CTA and FFRCT over 18 months.

Intervention

Icosapent ethyl

Comparator

Placebo

Outcome

FFRCT value in the distal coronary segment from baseline to follow-up in the most diseased vessel per patientsurrogate

Icosapent ethyl significantly improves coronary physiology as assessed by FFRCT over 18 months compared to placebo, providing a potential mechanism for its clinical benefits in reducing ischemic events.

Main Result

Absolute Event Rate: -0.01% vs -0.09%

p-value: p=0.03

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.