EVAPORATE Interim Analysis: Icosapent Ethyl Plus Statin Therapy Significantly Slowed Plaque Progression

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The addition of IPE significantly slowed coronary plaque progression as compared to placebo over 9 months for 4 of the 5 secondary end points.

Matthew J. Budoff, MD

The REDUCE-IT trial demonstrated that icosapent ethyl (IPE) has the ability to reduce cardiovascular events by 25%, but investigators have yet to fully explore the mechanism of benefit.

Until now.

A research team led by Matthew J. Budoff, MD, with LA BioMed, set out to evaluate whether the addition of IPE, along with diet and statin therapy, can lead to a greater change from baseline in plaque volume measured by serial multidetector computed tomography (MDCT) compared with placebo in patients with high triglycerides (TG).

In interim findings presented in a late-breaking session at the American Heart Association (AHA) 2019 Scientific Sessions in Philadelphia, the EVAPORATE study demonstrated that the addition of IPE significantly slowed coronary plaque progression as compared to placebo over 9 months for 4 of the 5 secondary end points.

However, the mechanistic study’s primary end point of progression rates of low attenuation plaque was not statistically significant as of the 9-month interim mark. The trial will continue to 18 months.

Patients with coronary atherosclerosis, according to MDCT (1 or more angiographic stenoses with ≥20% narrowing), were included in the prospective, randomized, double-blind, placebo-controlled, multicenter study. Inclusion criteria comprised age ≥45 years, fasting TG levels ≥150 mg/dL and <500 mg/dL, LDL-C >40 mg/dL and ≤100 mg/dL, and on stable statin therapy (±ezetimibe) for ≥4 weeks prior to qualifying measurements for randomization.

Exclusion criteria included severe (NYHA class IV) heart failure, contrast allergy, renal insufficiency (eGFR <60), and hypersensitivity to fish and/or shellfish.

Patients had no history of myocardial infarction, stroke, or life-threatening arrhythmia within the prior 6 months, and no history of coronary artery bypass grafting. Baseline characteristics were well-balanced between the treatment and placebo arms.

A total of 80 patients were randomized to receive either IPE 4g/d or placebo.

Investigators performed interim scans at 9 months and are currently following the group for an additional 9 months with MDCT at 0, 9, and 18 months.

The primary end point was progression rates of low attenuation plaque volume as measured by MDCT and defined as -50 to 50 HU, with secondary end points including plaque morphology and composition, markers of inflammation (Lp-PLA2), and LDL-C and HDL-C.

The 9-month interim analysis shows that IPE slowed progression by 21% for low attentuation plaque (p=0.469), 19% for total non-calcified plaque (p=0.010), 42% for total plaque (p=0.0004), 57% for fibrous plaque (p=0.011), and 89% for calcified plaque (p=0.001).

Investigators also demonstrated that progression rates on mineral oil placebo is similar to a non-mineral oil placebo cohort using same the methodology, scanner, and laboratory, showing that the outcomes were benefits of IPE and not a harm of mineral oil.

The study, “Effect of Icosapent Ethyl on Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides (200-499mg/dl) on Statin Therapy (EVAPORATE Study),” was presented Monday, November 18, 2019, at AHA 2019.