Key result
Icosapent ethyl 4 g/day did not significantly change the progression of low attenuation plaque volume compared to placebo at 9 months (74% vs 94%, p=0.469), though it slowed progression of other plaque types.
Why the study?
Although icosapent ethyl added to statin therapy reduced cardiovascular events in REDUCE-IT, its effects on coronary atherosclerosis progression had not yet been fully investigated.
Does icosapent ethyl reduce coronary plaque progression in statin-treated patients with elevated triglycerides and coronary atherosclerosis?
RCT (n=80)
Double-blind
1:1
Yes
Does icosapent ethyl reduce coronary plaque progression in statin-treated patients with elevated triglycerides and coronary atherosclerosis?
Absolute Event Rate: 74% vs 94%
p-value: p=0.469
In statin-treated patients with elevated triglycerides, icosapent ethyl significantly slowed the progression of total and non-calcified coronary plaque at 9 months compared to placebo, providing a mechanistic basis for its cardiovascular event reduction.
No effect on low-attenuation plaque at 9 months; challenges expectations for icosapent ethyl on vulnerable plaque in statin-treated patients.
AIMS: Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. METHODS AND RESULTS: EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40-115 mg/dL, and persistently high triglyceride levels (135-499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (-1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. CONCLUSION: EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial. CLINICALTRIALS. GOVIDENTIFIER: NCT029226027.
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Budoff et al. (2020) conducted an RCT in Coronary atherosclerosis with elevated triglycerides (n=80). Icosapent ethyl vs. Placebo (mineral oil) was evaluated on Change in low attenuation plaque (LAP) volume (p=0.469). Icosapent ethyl 4 g/day did not significantly change the progression of low attenuation plaque volume compared to placebo at 9 months (74% vs 94%, p=0.469), though it slowed progression of other plaque types.
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