An interim analysis showed that icosapent ethyl did not significantly slow progression of low-attenuation plaque in comparison with placebo in patients with coronary atherosclerosis who were already receiving statins, according to results presented Monday at the American Heart Association Scientific Sessions in Philadelphia.
The EVAPORATE study was a randomized, double-blind, placebo-controlled trial designed to evaluate the effects of 4 g/day of icosapent ethyl on atherosclerotic plaque in statin-treated patients with coronary atherosclerosis, fasting triglyceride levels of 135 to 499 mg/dL, and low-density lipoprotein-cholesterol (LDL-C) levels of 40 to 115 mg/dL at least 4 weeks before randomization.
Matthew J. Budoff, MD, of the Lundquist Institute, Torrance, California, and colleagues wrote the abstract that Budoff presented. In the abstract, the authors noted the positive results of the REDUCE-IT trial.
The U.S. Food and Drug Administration previously approved icosapent ethyl (Vascepa, Amarin) to reduce triglyceride levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. The REDUCE-IT trial showed benefit of icosapent ethyl in patients with triglyceride levels of 135 to 499 mg/dL. Based on those results, an FDA advisory panel recommended on Thursday that the indication for icosapent ethyl be expanded to patients with those lower triglyceride levels.
The primary endpoint of the EVAPORATE trial is progression rate of low-attenuation plaque at 18 months. The results presented Sunday were a prespecified interim analysis of the endpoints at 9 months. At 9 months, icosapent ethyl was not on track to meet the primary endpoint, as the medication slowed progression of low-attention plaque by 21%, which was not statistically significant compared with placebo (progression with icosapent ethyl 74% vs. placebo 94%, p=0.469), as shown by computed tomography angiography. Also, icosapent ethyl showed an increase, albeit statistically nonsignificant, in fibrofatty plaque compared with placebo (icosapent ethyl 87% increase vs. placebo 25% increase, p=0.65).
Four secondary plaque measurements did show significantly slowed progression in the treatment arm as compared with the placebo arm:
- 19% slowed progression for total non-calcified plaque (icosapent ethyl 35% increase vs. placebo 43% increase, p=0.01)
- 42% slowed progression for total plaque (icosapent ethyl 15% increase vs. placebo 26% increase, p=0.0004)
- 57% slowed progression for fibrous plaque (icosapent ethyl 17% increase vs. placebo 40% increase, p=0.011)
- 89% slowed progression for calcified plaque (icosapent ethyl 1% decrease vs. placebo 26% increase, p=0.001).
A total of 106 patients were screened, and 80 patients were randomized to icosapent ethyl or placebo, 40 in each arm. According to the interim results, 30 patients in the treatment arm and 37 in the placebo arm completed 9-month follow-up.
The EVAPORATE study was funded by Amarin Pharma Inc., Bridgewater, New Jersey.