Icosapent ethyl reduces coronary plaque at 18 months: EVAPORATE final results
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Icosapent ethyl as an adjunct to statin therapy significantly reduced multiple plaque components, including low-attenuation plaque, at 18 months, compared with placebo, according to final results of the EVAPORATE trial.
The findings build on previously reported interim data that demonstrated a very early effect of icosapent ethyl (Vascepa, Amarin) on plaque volume at 9 months, with sustained and increasing significance by 18 months, Matthew Budoff, MD, director of cardiovascular CT at The Lundquist Institute and professor of medicine at the David Geffen School of Medicine at UCLA, said during a presentation at the virtual European Society of Cardiology Congress.
EVAPORATE is the first demonstration of imaging results with icosapent ethyl using multidetector coronary CT angiography.
“These data highlight the early and sustained impact of icosapent ethyl on the atherothrombotic burden in the high-risk population,” Budoff said.
Plaque volumes differed at 18 months
The EVAPORATE trial was based on REDUCE-IT, in which icosapent ethyl 4 g per day was superior to placebo for reducing risk for ischemic events in patients with elevated triglycerides at high CV risk despite statin therapy. The EVAPORATE investigators hypothesized that icosapent ethyl could have anti-atherosclerotic properties.
The randomized, double-blind, placebo-controlled trial enrolled 80 patients who had coronary atherosclerosis documented by multidetector CT (at least one angiographic stenosis with 20% or greater narrowing), were receiving statin therapy and had persistent, elevated triglyceride levels (mean, 259 mg/dL). Patients were randomly assigned to receive icosapent ethyl 4 g per day or placebo and underwent multidetector CT scans at baseline, 9 months and 18 months.
At 18 months, the primary endpoint of low-attenuation plaque volume was reduced by 17% in the icosapent ethyl group, but increased by 109% in the placebo group (P = .0061).
Budoff also reported significant differences in other plaque volumes, which at 18 months had regressed in the icosapent ethyl group and progressed in the placebo group, including total plaque (–9% vs. +11%; P = .0019), total noncalcified plaque (–19% vs. +9%; P = .0005), fibrofatty plaque (–34% vs. +32%; P = .0002), fibrous plaque (–20% vs. 1%; P = .0028) and calcified plaque (–1% vs. +15%; P = .0531).
The differences in changes in plaque volume between the groups remained significant after adjustment for age, sex, diabetes, hypertension and baseline triglyceride level (P < .01 for all). Dense calcium was the only secondary endpoint that did not achieve a significant difference between the two groups (P = .053).
The researchers performed an additional analysis, to address concerns about the effect of the mineral oil placebo contributing to the endpoint, potentially causing some of the plaque progression or adverse events in control group of the REDUCE-IT trial compared with the group assigned the active compound. Rates of plaque changes in patients randomly assigned to receive mineral oil placebo in the EVAPORATE study were compared with rates of plaque changes in the placebo arm of a second study that used a cellulose-based placebo. Budoff said there was no difference in plaque progression between mineral oil and cellulose-based placebos, yielding high confidence that the benefits seen with icosapent ethyl in EVAPORATE represent a beneficial effect of this therapy on atherosclerosis as opposed to harm from mineral oil.
Budoff noted several limitations of the study, including its small sample size and lack of power for long-term outcomes.
The data were simultaneously published in European Heart Journal.
‘Consistent benefits’
The coronary plaque reduction demonstrated in EVAPORATE is consistent with the benefits of icosapent ethyl on CV event outcomes demonstrated in REDUCE-IT. As Healio reported earlier this year, REDUCE-IT REVASC showed a very early coronary revascularization benefit by 11 months in patients treated with icosapent ethyl.
“To the best of our knowledge, this is the first elegant marriage of clinical trial results and imaging demonstrating consistent benefits of icosapent ethyl on both outcomes and plaque reduction,” Budoff said.
Reference:
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Budoff MJ, et al. Late-Breaking Science in Lipids. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).
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