Plaques May Be Key to Vascepa's Role in Preventing CV Events

Early data from a study examining how a purified fish oil pill reduces cardiovascular (CV) events suggest that it helps slow the advance of various coronary plaques that increase the risk of heart attacks.

Data from EVAPORATE, presented Monday at the 2019 American Heart Association (AHA) Scientific Sessions in Philadelphia, Pennsylvania, may be the start of answering a question that has baffled the research community: Just how does icosapent ethyl, sold as Vascepa, prevent heart attacks in patients with high triglycerides?

While the study’s primary end point—reduced progression of a dangerous, fatty substance called low attenuation plaque, measured with a computed tomography angiogram—had not reached statistical significance, a commentator at the 2019 AHA Scientific Sessions noted that the data presented are an interim analysis, and “it’s very early.”

A year ago, results from REDUCE-IT trial dazzled attendees at the AHA Sessions: Icosapent ethyl, sold by Amarin as Vascepa since 2012 to treat high triglycerides, was shown to reduce CV events by 25%. Follow-up data released in March showed that the 4-g daily dose reduced first and future events by 30%, and last week an FDA advisory committee voted unanimously to support Amarin’s request for a cardiovascular indication for the pill.

Except, as AHA moderator Donald Lloyd-Jones, MD, ScM, noted, “We still don’t really understand yet how that drug works.”

And that’s the point of EVAPORATE. Matthew Budoff, MD, professor of medicine at UCLA School of Medicine, said this is a “mechanistic study,” to understand how REDUCE-IT produced its findings. By measuring patients’ plaque levels before, during, and at the end of the 18-month period, researchers hope to gain insights on how icosapent ethyl works alongside statins.

Nine months into EVAPORATE—the midway point of the trial—patients taking icosapent ethyl have reduced the advance of low attenuation plaque by 21% compared with those taking placebo; however, the difference showed a P value of .469.

Several secondary plaque measures have reached significance. Compared with placebo, those taking icosapent ethyl have seen the following reductions in plaque progression:

• 19% for total non-calcified plaque (P = .010)
• 42% for total plaque (P = .0004)
• 57% for fibrous plaque (P = .011)
• 89% for calcified plaque (P = .001)

The interim data show an increase in fibrofatty plaque, but also not at the level of statistical significance (P = .650).

Commentator Stephen Nicholls of Monash University in Australia noted that the small size of EVAPORATE—just 80 patients—means it will be critical to keep track of all the participants to yield a meaningful result. He said more clinical trials will be needed.

It’s clear so far that reduction of triglycerides on its own is not producing the dramatic drop in CV events, Nicholls said. This raises the question of whether other patient groups should be taking icosapent ethyl.

The fact that EVAPORATE has not yet met its primary end point is not a cause for worry. “I don’t see this as a failed study,” he said.