The following is a summary of “PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection,” published in the January 2023 issue of Cardiology by Navarese, et al.

The severity of the inflammatory response during COVID-19 is associated with negative results. Low-density lipoprotein receptor homeostasis is impacted by proprotein convertase subtilisin/kexin type 9 (PCSK9), which may impact vascular inflammation and the COVID-19 inflammatory response. For a study, researchers sought to compare the clinical and laboratory results of PCSK9 inhibition to placebo in patients with severe COVID-19.

60 patients hospitalized for severe COVID-19 with ground-glass opacity pneumonia and arterial partial oxygen pressure to the fraction of inspired oxygen ratio of ≤300 mm Hg were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or a placebo. The study was double-blind, placebo-controlled, and multicenter. At 30 days, the main outcome was mortality or the requirement for intubation. Change in circulating interleukin (IL)-6 at 7 and 30 days from baseline was the primary, secondary objective.

In comparison to placebo, patients who were randomly assigned to receive the PCSK9 inhibitor had decreased rates of mortality or the requirement for intubation after 30 days (23.3% vs. 53.3%, risk difference: –30%; 95% CI: –53.40% to –6.59%). With the PCSK9 inhibitor, serum IL-6 decreased over time more slowly than with the placebo (30-day decline: –56% vs. –21%). Lower mortality was seen with PCSK9 inhibition compared to placebo in patients whose baseline IL-6 levels were higher than the median (risk difference: –37.50%; 95% CI: –68.20% to –6.70%).

In severe COVID-19, PCSK9 inhibition decreased IL-6 levels and the main outcome of mortality or the requirement for intubation compared to placebo. Patients who had more severe inflammation at the time of randomization fared better with PCSK9 inhibition than with a placebo, suggesting that the degree of inflammation may influence the therapeutic outcomes.

Reference: jacc.org/doi/10.1016/j.jacc.2022.10.030