As the COVID-19 pandemic continues, ongoing research remains underway to determine effective treatments for improving patient outcomes and reducing rates of hospitalization and/or death. Two separate trials presented Nov. 15 as part of AHA 2021 explored use of icosapent ethyl (IPE) and P2Y12 inhibitors, respectively, with results from both showing no significant benefit with either.

In findings from the PREPARE-IT 2 trial, a high dose of pure IPE did not substantially reduce rates of hospitalization and/or death among non-hospitalized adults with COVID-19.

Researchers randomized 2,000 adults who had tested positive for COVID-19 and were symptomatic for 7 days or less but who did not require hospitalization, to receive either IPE or placebo. Those in the IPE group received 8 grams (four capsules) every 12 hours with food for three days, followed by 4 grams (two capsules) every 12 hours with food starting the fourth day, through day 28. A subgroup of patients was asked to self-report the severity of their symptoms using a validated symptom diary at the start of the study and at 28 days.

Overall results found that IPE treatment was safe and well tolerated, but it did not lead to statistically significant reductions in mortality or hospitalization rates. While researchers did note a small positive trend with the IPE treatment, they also noted a slightly higher rate of participants who stopped taking the pills in the IPE group.

“Based on observable outcomes, loading doses of IPE were safe and well tolerated,” said study author Rafael Díaz, MD. “It’s unclear if a larger trial might support or refute the positive trends noted here with high- high-dose IPE treatment.”

In the ACTIV-4a trial, use of P2Y12 inhibitors in non-critically ill hospitalized COVID-19 patients did not result in a greater number of days alive and free of cardiovascular or respiratory organ support. However, researchers did observe a lower rate of major bleeding in the usual care group compared with the P2Y12 inhibitor group (~1% absolute risk increase).

The trial randomized 562 patients to either a P2Y12 inhibitor (ticagrelor was used in 63%; clopidogrel was used in 37%) or usual care. Participants in both groups were on average 53 years of age, slightly more than 40% were female, around 62% were White, more than 40% were Hispanic, and more than 50% were obese. Additionally, 43.7% of those in the P2Y12 inhibitor group and 55.8% in the usual care group had cardiovascular disease. Duration of P2Y12 inhibitor treatment was 14 days or until hospital discharge, whichever came first.

Results found the composite of death or organ support was 26% in the P2Y12 inhibitor group compared with 22% in the usual care group. Major bleeding or in-hospital death occurred in 18 of the 293 patients assigned to P2Y12 inhibitors, compared with 10 of the 269 assigned usual care. Major bleeding alone occurred in six vs. two patients, respectively.

Enrollment was discontinued in the non-critically ill group on June 19 after a planned adaptive analysis demonstrated that the statistical criterion for futility was met. Additional research on P2Y12 inhibitor use with COVID-19 patients is ongoing.

Keywords: AHA Annual Scientific Sessions, American Heart Association, AHA21

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