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Impact of PCSK9 inhibitor on T lymphocyte subsets and cytokines in patients with acute ischemic stroke: an exploratory analysis of a randomized clinical trial

Year: 2025

Type: article

Abstract: Background PCSK9 inhibitors are lipid-lowering agents with pleiotropic properties including immune-inflammatory modulation. However, the effects of PCSK9 inhibitors on the peripheral immune profile of patients with acute ischemic stroke (AIS) remain unknown. In this analysis, we aim to further investigate the impact of PCSK9 inhibitor evolocumab on clinical outcomes, immune responses, and cytokines in AIS patients. Methods In this study, a total of 100 patients with AIS were included for the current analysis ( n = 50 for combination therapy of evolocumab and atorvastatin, PI group, n = 50 for atorvastatin monotherapy, AT group). Blood samples were collected at baseline and 7 days after evolocumab administration. T lymphocyte subsets, T helper (Th) cell subsets, and T cell compartments were identified by flow cytometry. The concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-a (TNF-a) were also measured. Results Compared with the AT group, patients in the PI group had a significantly lower incidence of early neurological deterioration (END) ( p = 0.032). Also, the PI group had a significantly higher proportion of favorable functional outcomes at 90 days than the AT group ( p = 0.001). Moreover, the plasma IL-6 concentration was significantly lower in the PI group than in the AT group at 7 days after treatment ( p = 0.023). However, the T lymphocyte subsets, Th cell subsets, and T cell compartments were not statistically different between the two groups at baseline or 7 days after treatment ( p > 0.05). Conclusions This study demonstrated that adjunctive evolocumab therapy significantly improved clinical outcomes and inhibited the elevation of the plasma IL-6 compared to atorvastatin monotherapy in AIS patients, whereas peripheral blood T lymphocyte subsets did not change in this trial. Trial registration http://www.chictr.org.cn ; Identifier: ChicTR2200059445. Date of registration: 29 April 2022.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2025.1688553