Effect of PCSK9 inhibition in combination with statin therapy on intracranial atherosclerotic stenosis: A high-resolution MRI study

Abstract

IntroductionIntracranial atherosclerotic stenosis (ICAS) is a common cause of stroke worldwide. Evolocumab, a proprotein convertase subtilisin/kexin type-9 inhibitor (PCSK9i), effectively lowers low-density lipoprotein (LDL) and produces favorable changes in coronary atherosclerosis. This study aimed to determine the effects of PCSK9i on intracranial plaques in moderate-intensity statin-treated individuals with ICAS.MethodsThis prospective, observational study monitored the imaging and clinical outcomes of individuals with ICAS who were consecutively treated with moderate-intensity statins with or without PCSK9i. Individuals underwent monthly visits and repeat high-resolution MRI (HR-MRI) at week 12. The primary outcome was a change in HR-MRI after 12 weeks of treatment and the secondary outcome was major vascular events during follow-up.ResultsForty-nine individuals were studied (PCSK9i group: 26 individuals with 28 abnormal vascular regions; statin group: 23 with 27 regions). The PCSK9i group showed a significant reduction in the normalized wall index (0.83 vs. 0.86, p = 0.028) and stenosis degree (65.5 vs. 74.2%, p = 0.01). Similarly, a greater percentage of individuals with a good response to the efficacy of treatment were treated in the PCSK9i group than that in the statin group (75 vs. 44.4%, p = 0.021). The incidence of major vascular events was overall similar between the groups. The treatment options (OR = 8.441, p = 0.01) and prior diabetes (OR = 0.061, p = 0.001) were significantly associated with the efficacy of treatment.DiscussionStatin and PCSK9i combination treatment stabilized intracranial atherosclerotic plaques more often compared to statins alone, as documented by HR-MRI. Further study is warranted to determine if combination treatment improves clinical outcomes in ICAS.

Real-world effectiveness and safety of evolocumab in very high-risk atherosclerotic cardiovascular disease patients with acute ischemic stroke

“…The outcomes of a prospective cohort investigation carried out in Hong Kong, China, among patients with ischemic stroke, revealed that individuals with intracranial or extracranial arterial stenosis who received intensified lipid-lowering therapy experienced a notably greater decline in the likelihood of recurrent ischemic stroke as opposed to their counterparts without such stenosis [27][28][29] . Statin and PCSK9i combination treatment stabilized intracranial atherosclerotic plaques more often compared to statins alone, as documented by HR-MRI 30 . The PCSK9i group showed a…”

Refined imaging features of culprit plaques improve the prediction of recurrence in intracranial atherosclerotic stroke within the middle cerebral artery territory

“…Therefore, we incorporated the imaging features of plaque on HR-MR-VWI into a combination model with clinical and conventional imaging factors to enhance the predictive value of stroke recurrence. Other studies have also confirmed the contribution of clinical and conventional imaging factors, including age, diabetes, and AAE infarction, to stroke recurrence, as these factors can exacerbate plaque instability ( Tyrrell and Goldstein, 2021 , Ambreen et al, 2022 , Wu et al, 2023 ). The combination of clinical, imaging features, and plaque characteristics has a synergistic effect on predicting the risk of stroke recurrence.…”

Long-Term Efficacy and Tolerability of PCSK9 Targeted Therapy: A Review of the Literature

“…Evolocumab also significantly reduced the area of coronary atherosclerotic stenosis in nontarget lesions (− 13.6%) measured with quantitative coronary angiography 1 year after treatment following a primary percutaneous coronary intervention for ACS [ 53 ]. For intracranial atherosclerosis, evolocumab, in addition to moderate statin therapy, resulted in plaque stabilization and significantly reduced stenosis degree (74.2–65.5%, P = 0.010) of carotid arteries measured by high-resolution magnetic resonance imaging (MRI) [ 54 ]. Similar effects were observed in patients treated with alirocumab, where regression in plaque lipid content (20%) and neovasculature (17%) were observed after treatment with alirocumab in addition to low-dose statin therapy after 12 months [ 55 ].…”