Recent research indicates that the addition of evolocumab therapy may lead to significant regression of intracranial atherosclerotic plaque in patients with intracranial atherosclerotic stenosis (ICAS). This finding emerged from a study conducted by a team led by Xinzhi Hu, MD, at the Peking Union Medical College Hospital, which compared the outcomes of evolocumab add-on therapy with statin treatment alone over a six-month period.
The study builds upon previous research, such as the GLAGOV randomized clinical trial, which assessed the effectiveness of evolocumab and other PCSK9 inhibitors in managing coronary atherosclerosis. The GLAGOV trial found that patients receiving evolocumab achieved notably lower levels of low-density lipoprotein cholesterol compared to those on placebo.
Study Design and Patient Selection
The research team gathered data from a high-resolution magnetic resonance imaging (HR-MRI) database initiated in 2015, focusing on patients diagnosed with ICAS from 2016 to 2023. All participants underwent comprehensive evaluations that included medical history, conventional cranial MRI, HR-MRI, and blood tests.
To qualify for the study, patients had to demonstrate ICAS (50%-99%) confirmed via magnetic resonance angiography and show that the stenosis was a result of atherosclerosis. They were also required to have undergone HR-MRI evaluations at two points within the six-month timeframe while receiving continuous oral lipid-lowering therapy, which included statins and/or ezetimibe, with or without evolocumab.
Exclusions were made for patients with significant concurrent stenosis in extracranial vessels, nonatherosclerotic intracranial artery stenosis, or those who underwent surgical interventions during the follow-up period.
Findings and Implications
A total of 179 patients were included in the analysis, all of whom were on statin therapy. Among them, 50 patients received the evolocumab add-on, while 129 remained in the control group without evolocumab. The study revealed a significant difference in outcomes between the two cohorts. The evolocumab group exhibited a higher plaque response rate of 68% compared to 34.1% in the control group. Additionally, the group receiving evolocumab demonstrated a greater median reduction in plaque burden of -8.2% versus -1.9%, as well as a more substantial decrease in stenosis degree, with reductions of -15.3% compared to -5.4%.
The researchers utilized logistic and linear regression analyses to understand the relationship between evolocumab therapy and these endpoints, finding significant associations. The adjusted odds ratio for plaque response was calculated at 6.67, and the percentage reductions in plaque burden and stenosis degree were noted as -7% and -20.3%, respectively.
These findings suggest that evolocumab may represent a more effective treatment strategy for reversing intracranial atherosclerotic plaques. Dr. Hu and colleagues emphasized that while the results are promising, further prospective, randomized controlled trials are necessary to confirm these observations and fully understand their clinical implications.
The study was published in the Journal of the American Heart Association in March 2025.
