Abstract Body: Rationale
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54% to 75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g., Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored.
Aim and hypothesis
To determine if combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone.
Sample size estimates
With a sample size of 1000 subjects, a two-sided of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden.
Methods and design
This is an investigator-initiated multicenter, randomized, open-label, outcome assessor–blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) will be randomized 1:1 into two groups to receive either Evolocumab 140 mg every two weeks with statin therapy or statin therapy alone.
Study outcomes
The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and the end of the 24-week treatment period.
Discussion
This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data.
Trial registration number: ChiCTR2300068868; https://www.chictr.org.cn/