Highly-purified EPA does not reduce clinical outcomes in non-hospitalized COVID-19 patients

PREPARE IT-2: A pragmatic trial evaluating icosapent ethyl (IPE) in non-hospitalized patients with a positive diagnosis of COVID-19 to reduce hospitalization rates and complications

News - Nov. 15, 2021

Presented at the American Heart Association’s Scientific Sessions 2021 by: Rafael Diaz, MD - Rosario, Argentina

Introduction and methods

Aim of the study

The objective of the PREPARE IT-2 was to investigate the effect of icosapent ethyl on planned COVID-19-related hospitalizations or mortality in patients with a diagnosis of COVID-19 assessed at 28 days.

Study design

The study enrolled individuals ≥40 years with a confirmed COVID-19 diagnosis who were within 7 days from the onset of symptoms. They had no indication for hospitalization.

2052 Patients were randomized to the treatment group with 8 gr icosapent ethyl for the first 3 days followed by 4 gr icosapent ethyl thereafter (day 4-28) or to the placebo group.

Primary outcome

The primary outcome was COVID-19-related hospitalization (indication for hospitalization or actual hospitalization) or death.

Main results

  • The event rate of the primary outcome was 11.2% in the treatment arm and 13.7% in the control arm (HR 0.84, 95%CI:0.65-1.08, P=0.166).
  • Secondary endpoints, such as COVID-19 hospitalization or death, or not alive or not out of the hospital at day 28, were not different between the 2 arms.
  • There was no difference in adverse events between the treatment and control groups.


There was no difference in the primary outcome in the icosapent ethyl group and the control group in patients with COVID-19. Icosapent ethyl was well tolerated, but there was a slightly higher discontinuation rate compared to placebo. The presenter Rafael Diaz concluded that larger RCTs powered for ~15% risk reduction by icosapent ethyl are needed to examine whether icosapent ethyl may improve the outcomes of patients with COVID-19.


The discussant Erin Michos, MD (John Hopkins, Baltimore, MD, USA) repeated the findings of the REDUCE-IT trial with icosapent ethyl. It has been suggested that benefits of icosapent ethyl are beyond triglyceride lowering and brought up other potential properties, such as anti-inflammatory and anti-thrombotic effects. It has been assumed that inflammation plays a causal role in the progression of COVID-19. COVID-19 is also associated with a hypercoagulable state. This was the rationale for testing icosapent ethyl in this population.

The previous PREPARE IT-1 trial included individuals at risk for COVID-19, but there was no effect of icosapent ethyl on the prevention of COVID-19. Then, a small study of 100 patients was performed in COVID-19 patients and showed that icosapent ethyl reduced CRP and improved symptoms. Here, it was tested in a larger population of 2000 patients.

Michos said that the non-significant findings may be due to the lower rate of events than expected. Reassuring was the finding that 8 gr in the first days did not increase atrial fibrillation and bleeding. A larger trial is needed to get a definite answer whether icosapent ethyl may be helpful in these patients, but a large prevention strategy would be the broad adoption of vaccinations globally, Michos said.

- Our reporting is based on the information provided at the American Heart Association’s Scientific Sessions 2021 -

Watch a video by Rafael Diaz on this trial

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