Effects of PCSK9 inhibitor evolocumab on preventing early neurological deterioration in acute ischemic stroke patients with or without large artery atherosclerosis: a subgroup analysis of a randomized trial.

Abstract

Background: Our previous study has demonstrated the preventive effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor on early neurological deterioration (END) in patients with acute non-cardiogenic ischemic stroke. Here, we performed a post hoc subgroup analysis to investigate whether the large artery atherosclerosis (LAA) subtype contributed to the clinical outcomes.

Methods: According to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, patients were divided into LAA and small vessel occlusion (SVO) subgroups. In each subgroup, patients were further subdivided into combination therapy of evolocumab and atorvastatin (PI group) and atorvastatin monotherapy (AT group). The primary outcome was END within 7 days, defined as a ≥ 2-point National Institutes of Health Stroke Scale (NIHSS) score increase or NIHSS motor score ≥ 1-point compared with baseline.

Results: A total of 272 patients were included: 186 were categorized into the LAA subtype (93 in the PI group and 93 in the AT group) and 86 into the SVO subtype (43 in the PI group and 43 in the AT group). Compared with AT group, the primary analyses showed a significantly lower incidence of END with PI group in the LAA subtype (14.0% versus 28.0%; RR, 0.45; 95% CI, 0.26 to 0.80; p = 0.006), but not in the SVO subtype (11.6% versus 16.3%; RR, 0.77; 95% CI, 0.26 to 2.33; p = 0.649). Similar results were observed in terms of favorable functional Outcome at 90 days, combination therapy of evolocumab and atorvastatin was significantly associated with a high proportion of modified Rankin Scale scores of 0-2 at 90 days in the LAA group (81.7% versus 61.3%; RR, 1.39; 95% CI, 1.18 to 1.65; p < 0.001), but not in the SVO subtype (86.0% versus 74.4%; RR, 1.16; 95% CI, 0.95 to 1.42; p = 0.157). Other outcomes were similar between the two treatment groups in patients with LAA or SVO subtypes.

Conclusions: Among patients with LAA subtype stroke, combination therapy of evolocumab and atorvastatin may be superior to atorvastatin monotherapy regarding preventing END.

Trial registration: http://www.chictr.org.cn . Identifier: ChicTR2200059445. Date of registration: 29 April 2022.