American Heart Association

American Heart Association

Source:

Diaz R, et al. LBS.06. Fish Oil and Cholesterol: Recipes for CVD Prevention? Presented at: American Heart Association Scientific Sessions; Nov. 13-15, 2021 (virtual meeting).

Disclosures: The study was funded by Amarin. Diaz reports receiving grants from Amarin, Dalcor, Lepetit SA and PHRI. Bhatt reports having research contracts with Amarin.
November 15, 2021
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Icosapent ethyl does not reduce COVID-19 hospitalization, death despite favorable trends

Source:

Diaz R, et al. LBS.06. Fish Oil and Cholesterol: Recipes for CVD Prevention? Presented at: American Heart Association Scientific Sessions; Nov. 13-15, 2021 (virtual meeting).

Disclosures: The study was funded by Amarin. Diaz reports receiving grants from Amarin, Dalcor, Lepetit SA and PHRI. Bhatt reports having research contracts with Amarin.
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Treatment with icosapent ethyl was safe and well-tolerated but did not reduce risk for hospitalization or death among COVID-19 outpatients compared with placebo, though researchers observed favorable trends for benefit.

Data from the PREPARE-IT 2 study were presented at the American Heart Association Scientific Sessions.

“We observed a lower rate of the primary outcome with icosapent ethyl vs. placebo, but that difference was not statistically significant,” Rafael Diaz, MD, director of Estudios Clínicos Latino América at Instituto Cardiovascular de Rosario in Argentina, said during a press conference. “The very high loading dose was well-tolerated compared with placebo, although there was a slightly higher rate of discontinuations in the active arm.”

As Healio previously reported, data from a small, first-in-human study presented at the National Lipid Association Scientific Sessions in December 2020 showed icosapent ethyl (Vascepa, Amarin), a pharmaceutical-grade omega-3 fatty acid, reduced levels of inflammatory biomarkers and improved symptoms in patients with COVID-19. The study offered the first evidence of an early anti-inflammatory effect of icosapent ethyl in symptomatic patients. The PREPARE-IT 1 study, presented at the European Society of Cardiology Congress in August, demonstrated high-dose icosapent ethyl for 60 days did not prevent incident SARS-CoV-2 infection among healthy participants who did not have prior known infection, with or without COVID-19 vaccination.

Nonsignificant, favorable trend observed

For PREPARE-IT 2, researchers assessed if icosapent ethyl might be effective in reducing risk for COVID-19-related morbidity or mortality in symptomatic nonhospitalized patients. They also examined the safety and tolerability of a high loading dose.

The study included 2,052 adults aged at least 40 years with a confirmed positive COVID-19 diagnosis no more than 7 days from onset of symptoms and without a clear indication for hospitalization, randomly assigned to icosapent ethyl (n = 1,010) or placebo (n = 1,042). Participants in the icosapent ethyl arm received an initial loading dose of 8 g daily for the first 3 days — double the FDA-approved dose — followed by a 4-g daily dose from day 4 to day 29. The primary endpoint was COVID-19-related hospitalization or death at 28 days. A subgroup of patients completed the influenza patient-reported outcome (FLU-PRO) score, a 32-item score across six domains, at baseline and again at 28 days.

Compared with placebo, researchers observed fewer COVID-19 hospitalizations or deaths among participants in the icosapent ethyl arm (11.16% vs. 13.69%); however, the HR of 0.84 did not reach statistical significance (95% CI, 0.65-1.08; P = .166).

Across secondary outcomes, researchers also observed numerically fewer COVID-19 hospitalizations, deaths or new requirements for mechanical ventilation in the icosapent ethyl arm vs. placebo (OR for COVID-19 hospitalization or death = 0.78; 95% CI, 0.55-1.12; P = .18; OR for new mechanical ventilation = 0.76; 95% CI, 0.26-2.08; P = .648). Four patients in the icosapent ethyl arm and eight patients in the placebo arm died (OR = 0.52; 95% CI, 0.11-1.95; P = .388).

“All secondary outcomes were nonsignificant, although all trended in the same [positive] direction,” Diaz said.

Icosapent ethyl was safe and well tolerated, with no between-group differences in adverse events. There was no atrial fibrillation/flutter or major bleeding observed in either group.

Diaz said larger, randomized trials adequately powered for a 15% relative risk reduction are needed to establish whether icosapent ethyl may have a role in the management of COVID-positive outpatients.

Demonstrating safety

Deepak L. Bhatt

The PREPARE-IT 2 study was an opportunity for investigators to assess an already-approved treatment that could potentially be easily deployed and repurposed for COVID-19-positive outpatients, a group without many treatment options, according to Cardiology Today Intervention Section Editor Deepak L. Bhatt, MD, MPH, executive director of interventional cardiology programs at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School.

“We found that the loading dose of icosapent ethyl was well-tolerated, and it was not associated with many adverse events vs. placebo,” Bhatt, also the PREPARE-IT 2 study chair, said in an interview. “In the REDUCE-IT study, we did see an increased risk for bleeding and atrial fibrillation in the icosapent ethyl group, something we did not see here with COVID-19 outpatients.”

While the primary outcome was not significant, “directionally, it looked like there might be a positive benefit, in a trial that ended up being underpowered,” Bhatt said. "This would need to be confirmed in a large, adequately powered trial."

“It is useful to show this drug was not misbehaving in people who were actually sick, and that the loading dose was very well tolerated,” Bhatt said. “This opens the door in the future for studying the drug with the loading dose we used in PREPARE-IT 2 in ill patients with acute MI or stroke, for example.”