No reduction in COVID-19 hospitalization, death with icosapent ethyl

Treatment with icosapent ethyl did not reduce the rate of hospitalization or mortality among patients with SARS-CoV-2 infection, according to results of the PREPARE IT-2* trial presented at AHA 2021.

Participants were 2,052 patients aged ≥40 years (mean age ~52 years, ~53 percent female) with RT-PCR- or rapid test-confirmed SARS-CoV-2, ≤7 days since symptom onset, and no indication for hospitalization. They were randomized to receive icosapent ethyl 8 g (four capsules every 12 hours on days 1–3) followed by 4 g (two capsules every 12 hours; n=1,010) for days 4–28 or placebo (n=1,042).

At 28 days, COVID-19–related hospitalization (indication for hospitalization per blinded investigator or actual hospitalization) or mortality did not significantly differ between patients assigned to icosapent ethyl or placebo (11.16 percent vs 13.69 percent; hazard ratio [HR], 0.84, 95 percent confidence interval [CI], 0.65–1.08; p=0.166). [AHA 2021, LBS.06]

COVID-19 hospitalization or death also did not differ between the icosapent ethyl and placebo groups (5.38 percent vs 6.80 percent; HR, 0.78, 95 percent CI, 0.55–1.12; p=0.18).

At 28 days, there were also no significant differences between patients in the icosapent ethyl and placebo groups in terms of the rate of patients not alive or not out of hospital (1.02 percent vs 1.36 percent; odds ratio [OR], 0.74, 95 percent CI, 0.29–1.81; p=0.541) or with new requirement for mechanical ventilation (0.81 percent vs 1.07 percent; OR, 0.76, 95 percent CI, 0.26–2.08; p=0.648).

Total mortality rate also was similar between groups, with four and eight deaths in the icosapent ethyl and placebo groups, respectively (p=0.388), as was incidence of non-fatal myocardial infarction or stroke or death (four and 11 incidents, respectively; p=0.118).

Among hospitalized patients (53 and 70 in the icosapent ethyl and placebo groups, respectively), duration of hospitalization was longer in the icosapent ethyl vs placebo group (median 9 vs 7 days; mean difference, 3 days; p=0.010).

Change in self-reported symptom severity from baseline to 28 days, assessed through FLU-PRO score, was also similar between groups (median -0.41 vs -0.44; p=0.06).

Adverse event (AE) rate did not differ between patients in the icosapent ethyl and placebo groups (16.58 percent vs 14.85 percent; p=0.30). The most common AEs in the icosapent ethyl group were diarrhoea (7.28 percent), nausea (4.35 percent), and constipation (2.73 percent). There was one incidence of major bleeding in the placebo group and none in the icosapent ethyl group. More patients on icosapent ethyl than placebo permanently discontinued their treatment (7.08 percent vs 3.79 percent; p=0.001), primarily due to patient suspension (2.43 percent vs 1.21 percent; p=0.030) or both patient suspension and AEs (1.55 percent vs 0.30 percent; p=0.002).

“Icosapent ethyl (including the loading dose) was well tolerated compared with placebo, though there was a slightly higher rate of discontinuation,” noted study author Dr Rafael Díaz, director of Estudios Clínicos Latinoamérica in Rosario, Argentina. “It’s unclear if a larger trial might support or refute the positive trends noted here with high-dose icosapent ethyl treatment,” Díaz said.

*PREPARE IT-2: Prevention and Treatment of COVID-19 With EPA in Subjects at Risk - Intervention Trial