Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: final results of the EVAPORATE trial

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 changed 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.

Secular Decreasing Trend in Plasma Eicosapentaenoic and Docosahexaenoic Acids among Patients with Acute Coronary Syndrome from 2011 to 2019: A Single Center Descriptive Study

“…Several studies using intra-coronary imaging showed that circulating EPA levels were associated with lipid plaque volume, [ 24 ] and fibrous-cap thickness of the plaque [ 25 ]. A randomized control study evaluating coronary plaque change by multidetector computed tomography showed that treatment with n-3 PUFA formulation for 18 months significantly reduced the accumulation of low-attenuation plaque, which is a component of vulnerable plaque, compared to placebo [ 26 ]. Furthermore, a recent study showed that the proportion of EPA in serum phosphatidylcholine at the time of ACS was associated with further clinical adverse events [ 27 ].…”

The therapy with icosapent ethyl after the EVAPORATE trial: Between hope and skepticism

“…Icosapent ethyl represents high‐dose, purified eicosapentaenoic acid that showed promising results in the recent trials 5–8 . The REDUCE‐IT trial enrolled 8,179 patients who were followed for a median of 4.9 years 5 .…”

“…Some of them could be (i) antiplatelet effect that could be responsible for higher percentage of bleeding among patients who used this medication; (ii) anti‐inflammatory mechanism reflected in significant reduction of hsCRP in the icosapent ethyl group; and (iii) stabilization and/or regression of coronary atherosclerotic plaque. The later mechanism was investigated in the separate EVAPORATE trial that provided some answers, but also raised many questions 7,8 …”

“…The EVAPORATE trial investigated the volume and composition of coronary plaque in patients treated with icosapent ethyl and placebo 7,8 . Coronary atherosclerotic burden was assessed by coronary computed tomographic angiography (CCTA).…”

Cardiology on the cutting edge: updates from the European Society of Cardiology (ESC) Congress 2020

“…In this commentary, we summarized the most important trials presented during the 2020 Virtual ESC Congress (Table 1) which we predict will improve our everyday clinical practice [12][13][14][15][16][17][18][19][20][21][22][23][24]. The EMPEROR-Reduced (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction) trial [23] further strengthened the positive findings observed in the DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure) trial [25].…”