Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial
Key result
Icosapent ethyl drives significant LAP volume regression vs placebo in statin-treated patients with elevated triglycerides.
- P=0.0061
- n=80
Figures
Why the study?
Does icosapent ethyl reduce low-attenuation plaque volume in statin-treated patients with elevated triglycerides and coronary atherosclerosis?
Key Points
- To determine whether adding icosapent ethyl (4 g/day) to statin therapy leads to a greater change from baseline in coronary plaque volume compared with placebo in patients with elevated triglycerides.
- A randomized, double-blind, placebo-controlled trial enrolled 80 statin-treated patients with coronary atherosclerosis (≥20% stenosis by multidetector computed tomography) and persistently elevated triglycerides (median 259.1 ± 78.1 mg/dL).
- Participants received either icosapent ethyl (4 g/day) or placebo and underwent serial coronary computed tomographic angiography at baseline, 9 months, and 18 months to evaluate changes in low-attenuation plaque volume.
- Low-attenuation plaque volume significantly decreased by 17% in the icosapent ethyl group compared to a 109% increase in the placebo group over 18 months (P = 0.0061).
- Fibrous and fibrofatty plaque volumes regressed with icosapent ethyl and progressed with placebo (P < 0.01 for both), while dense calcium changes did not significantly differ between groups after multivariable adjustment (P = 0.053).
Study Design
Type
RCT (n=80)
Blinding
Double-blind
Randomization
randomized
Structured PICO
Does icosapent ethyl reduce low-attenuation plaque volume in statin-treated patients with elevated triglycerides and coronary atherosclerosis?
P
Population
80 statin-treated patients with coronary atherosclerosis and persistently elevated triglycerides, followed for 18 months.
I
Intervention
Icosapent ethyl 4 g/day as an adjunct to diet and statin therapy
C
Comparator
Placebo as an adjunct to diet and statin therapy
O
Outcome
Change in low-attenuation plaque (LAP) volume at 18 months measured by serial multidetector computed tomography (MDCT)surrogate
Main Result
Absolute Event Rate: -17% vs 109%
p-value: p=0.0061
Icosapent ethyl significantly regresses low-attenuation plaque volume over 18 months in statin-treated patients with elevated triglycerides, providing a mechanistic basis for the cardiovascular benefits observed in the REDUCE-IT trial.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“These data highlight the early and sustained impact of icosapent ethyl on the atherothrombotic burden in the high-risk population.”
“We know that atherosclerosis, or plaque in the coronary arteries, is associated with plaque rupture and future heart attacks and strokes. So when the REDUCE-IT trial showed a 25% reduction in heart attack and stroke and cardiovascular death using icosapent ethyl, we wanted to investigate why, or by what mechanism icosapent ethyl may benefit patients. So we undertook the EVAPORATE trial.”
“The study definitely shows a better outcome on plaque as measured by multidetector CT when comparing icosapent ethyl on plaque progression/regression. It is convincing that the drug reduced plaque volume, which would normally be expected to progress over time.”
Implication
Supports icosapent ethyl for residual risk reduction in statin-treated patients with elevated triglycerides; extends mechanistic insights from REDUCE-IT.
Abstract
AIMS: Despite the effects of statins in reducing cardiovascular events and slowing progression of coronary atherosclerosis, significant cardiovascular (CV) risk remains. Icosapent ethyl (IPE), a highly purified eicosapentaenoic acid ethyl ester, added to a statin was shown to reduce initial CV events by 25% and total CV events by 32% in the REDUCE-IT trial, with the mechanisms of benefit not yet fully explained. The EVAPORATE trial sought to determine whether IPE 4 g/day, as an adjunct to diet and statin therapy, would result in a greater change from baseline in plaque volume, measured by serial multidetector computed tomography (MDCT), than placebo in statin-treated patients. METHODS AND RESULTS: A total of 80 patients were enrolled in this randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis as documented by MDCT (one or more angiographic stenoses with ≥20% narrowing), be on statin therapy, and have persistently elevated triglyceride (TG) levels. Patients underwent an interim scan at 9 months and a final scan at 18 months with coronary computed tomographic angiography. The pre-specified primary endpoint was change in low-attenuation plaque (LAP) volume at 18 months between IPE and placebo groups. Baseline demographics, vitals, and laboratory results were not significantly different between the IPE and placebo groups; the median TG level was 259.1 ± 78.1 mg/dL. There was a significant reduction in the primary endpoint as IPE reduced LAP plaque volume by 17%, while in the placebo group LAP plaque volume more than doubled (+109%) (P = 0.0061). There were significant differences in rates of progression between IPE and placebo at study end involving other plaque volumes including fibrous, and fibrofatty (FF) plaque volumes which regressed in the IPE group and progressed in the placebo group (P < 0.01 for all). When further adjusted for age, sex, diabetes status, hypertension, and baseline TG, plaque volume changes between groups remained significantly different, P < 0.01. Only dense calcium did not show a significant difference between groups in multivariable modelling (P = 0.053). CONCLUSIONS: Icosapent ethyl demonstrated significant regression of LAP volume on MDCT compared with placebo over 18 months. EVAPORATE provides important mechanistic data on plaque characteristics that may have relevance to the REDUCE-IT results and clinical use of IPE.
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Cite This Study
Budoff et al. (2020) conducted an RCT in Coronary atherosclerosis with elevated triglycerides (n=80). Icosapent ethyl vs. Placebo was evaluated on Change in low-attenuation plaque (LAP) volume at 18 months (p=0.0061). Icosapent ethyl significantly reduced low-attenuation plaque volume by 17% compared to a 109% increase with placebo over 18 months (P=0.0061).