Vascepa Succumbs as COVID Treatment in ‘Underpowered’ Trial

Purified fish oil did not significantly reduce severe COVID-19 illness among infected outpatients, according to the PREPARE-IT 2 trial presented at the American Heart Association (AHA) virtual meeting.

In the study of more than 2,000 people, adults randomly assigned a regimen of icosapent ethyl (Vascepa) within days of developing COVID symptoms had an 11.2% incidence of dying or being indicated for coronavirus hospitalization within 28 days, which was not significantly better than the 13.7% for peers given placebo (HR 0.84, 95% CI 0.65-1.08).

Rates of actual COVID hospitalization and mortality were also no different between groups (5.4% vs 6.8%, respectively; OR 0.78, 95% CI 0.55-1.12). Additionally, icosapent ethyl failed to reduce the need for mechanical ventilation among hospitalized patients.

Larger randomized trials are needed to show if icosapent ethyl really reduces events in COVID patients, Rafael Diaz, MD, of Estudios Clínicos Latinoamérica in Rosario, Argentina, told the AHA audience.

“You saw everything trend in a favorable direction … This did not meet statistical significance because there were fewer events than expected,” perhaps related to the adoption of COVID vaccines, commented Erin Michos, MD, MHS, of Johns Hopkins School of Medicine in Baltimore, during an AHA press conference.

A trial aimed at showing a solid 15% reduction in events would require 7,000-8,000 patients, which in terms of practicality and feasibility is “very difficult to do nowadays,” Diaz said. “It’s maybe not worth it at this time in the pandemic.”

Icosapent ethyl contains pure eicosapentaenoic acid and is approved by the FDA for cardiovascular prevention on the basis of a 25% reduction in cardiovascular events in the REDUCE-IT trial. The effect was independent of triglyceride lowering and hypothesized to be related to an anti-inflammatory mechanism, while inflammation is thought to play a causal role in severe COVID-19 illness, according to Michos.

Last year, a pilot study had suggested the drug to reduce inflammation (according to C-reactive protein levels) and COVID-19 symptoms among infected outpatients. Although icosapent ethyl did not prevent SARS-CoV-2 infection in the subsequent PREPARE-IT 1 trial, investigators believed it could play a role in treating infected outpatients.

As such, Diaz and colleagues recruited patients for PREPARE-IT 2 who had been having COVID symptoms for no more than 7 days and did not need to go to the hospital at enrollment. There were 2,052 people randomized to the icosapent ethyl group or the placebo group.

The average age of the patients in the cohort was just over 51 years, and women constituted 53% of participants. Baseline characteristics were comparable between the study arms.

Icosapent ethyl recipients had a dosing schedule of 8 g daily for the first 3 days — a loading dose twice what is used for cardiovascular prevention — followed by 4 g daily through day 28.

Thus, it was notable that safety events were largely similar between icosapent ethyl and placebo groups, with diarrhea and nausea being the most commonly reported.

Michos remarked on the “very good safety” of double-dose icosapent ethyl in the present study, recalling there being an increased risk of atrial fibrillation in the icosapent ethyl arm of REDUCE-IT.

That trial was notable for an issue with the mineral oil placebo muddying the waters regarding icosapent ethyl’s magnitude and mechanisms of benefit in cardiovascular prevention. Other studies have tried and failed to show a heart benefit to omega-3 fatty acids.

Without more studies for clarification — such as another REDUCE-IT with neutral placebo — there is inefficiency in studying icosapent ethyl in the setting of COVID and the cardiovascular disease epidemic, commented current AHA president Donald Lloyd-Jones, MD, ScM, of Northwestern Feinberg School of Medicine in Chicago, following Diaz’s presentation.

He recommended that patients eat fish, not supplemental fish oil, for heart health.

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