Evolocumab Shows Plaque Regression in Intracranial Atherosclerotic Stenosis

Evolocumab add-on therapy was associated with intracranial atherosclerotic plaque regression in intracranial atherosclerotic stenosis (ICAS) versus statin therapy alone over a 6-month period, according to results from a recent trial.1

Recent studies, such as the GLAGOV randomized clinical trial, have investigated the efficacy of evolocumab, as well as PCSK9 inhibitors at large, in managing coronary atherosclerosis disease progression. GLAGOV in particular compared evolocumab against placebo, finding that the treatment group achieved lower mean time-weighted low-density lipoprotein cholesterol levels.2

“Few studies have focused on the effect of evolocumab on ICAS,” wrote Xinzhi Hu, MD, department of neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, and colleagues. “In this study, we sought to investigate whether evolocumab add-on therapy over 6 months achieves more intracranial plaque burden reduction than statin alone in patients with ICAS.”1

Investigators collected data from a real-world high-resolution magnetic resonance imaging (HR-MRI) database, established in 2015 by the Peking Union Medical College Hospital. Patients were chosen from the outpatient clinic in which all patients with ICAS were enrolled from 2016 to 2023 with HR-MRI follow-ups. All patients underwent comprehensive neuroimaging and clinical evaluations, including medical history, conventional cranial MRI, HR-MRI, and blood tests.1

For inclusion, patients were required to have ICAS (50%-99%) confirmed by magnetic resonance angiography in the middle cerebral artery M1 segment, internal carotid artery C6-7 segments, and vertebrobasilar artery; confirmation that intracranial stenosis was caused by atherosclerosis; 2 detections of HR-MRI over 6 months; and used continuous oral LLT, including statin and/or ezetimibe, with or without evolocumab, during the interval between the 2 HR-MRI scans.1

Participants were excluded if they had intracranial stenotic arteries with concurrent ipsilateral extracranial vessel stenosis (≥50%), had nonatherosclerotic intracranial artery stenosis (e.g., arterial dissection, moyamoya disease, and systemic vasculitis), underwent endovascular interventional treatment during follow-up, including intracranial stenting, angioplasty, and thrombectomy, or had poor HR-MRI image quality.1

The primary endpoint was noted as plaque response (plaque regression >5%), while secondary endpoints included the percentage of change in plaque burden and stenosis degree. Investigators utilized logistic and linear regression analyses to estimate the association between evolocumab use and all endpoints in both the general and subgroup analyses.1

A total of 179 patients were included in the study, all of whom were treated with statins. Of these, 50 patients were categorized into the evolocumab add-on cohort and 129 were placed in the no-evolocumab cohort. Investigators found a higher plaque response (68% versus 34.1%), greater plaque burden reduction (median [interquartile range (IQ)], -8.2% [-11.4% to -1.8%] versus -1.9% [-6.7% to 4.4%]), and stenosis degree reduction (-15.3% [-33.7% to -1.3%] versus -5.4% [-25.8% to 12.3%]) in the add-on therapy cohort.1

Adjusted regression analysis also displayed significant associations between evolocumab use and plaque response (odds ratio [OR], 6.67; 95% CI, 2.8 to 16.91), plaque burden reduction (-7%; 95% CI, -11.5% to -2.5%), and stenosis degree reduction (-20.3%; 95% CI, -31.7% to -7%). Subgroup analyses according to background statin intensity reaffirmed these consistent associations.1

“These preliminary findings suggest that this combination therapy may offer a potentially more effective strategy for reversing intracranial atherosclerotic plaque,” Hu and colleagues wrote. “However, further prospective, randomized controlled studies are warranted to confirm these observations and determine their clinical implications.”1

References

1. Hu X, Liu Y, Yuan W, et al. Evolocumab added to statin is associated with intracranial atherosclerotic plaque regression compared with statin alone. Journal of the American Heart Association. 2025;14(16). doi:10.1161/jaha.124.041251

2. Nicholls SJ, Puri R, Anderson T, et al. Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial. JAMA. 2016;316(22):2373–2384. doi:10.1001/jama.2016.16951