Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy Faculty of Medicine, The Hebrew University of Jerusalem, Israel; Department of Cardiology, Hadassah University Hospital, Israel.
Division of Clinical Pharmacy, Institute for Drug Research, School of Pharmacy Faculty of Medicine, The Hebrew University of Jerusalem, Israel.
Int J Cardiol. 2021 Jul 15;335:7-14. doi: 10.1016/j.ijcard.2021.04.025. Epub 2021 Apr 20.
It has been suggested that lipid lowering therapy causes impaired cognitive changes. The association between the use of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors and the risk of neurocognitive adverse events remains unclear. This meta-analysis aims to assess neurocognitive safety of PCSK9 inhibitors in randomized controlled trials (RCTs).
The research was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed (MEDLINE), Embase and Cochrane library were searched through September 2019. Selection criteria included RCTs that addressed to neurocognitive adverse events of participants using Alirocumab, Evolocumab or Bococizumab, with a follow up duration of at least 6 months. The search results were screened by two independent reviewers. Safety data from included papers were extracted. Random effects meta-analysis was used to pool results, and meta-regression was utilized when applicable. Twenty-one studies were included. Among 59,733 patients, 31,611 were treated with PCSK9 inhibitors. The follow-up period ranged from 24 weeks to 48 months. No significant difference in the incidence of neurocognitive adverse effects between the groups was identified (RR = 1.01, 95% CI: 0.86-1.19, I = 3%). Similar results were seen in subgroup analysis for each of the medications (alirocumab- RR = 0.88, 95% CI: 0.72-1.08, I = 0%, evolocumab- RR = 1.42, 95% CI: 0.74-2.73, I = 55%). A meta-regression analysis for evolocumab revealed that prolonged study duration was associated with decreased risk for neurocognitive adverse events (β = -0.0037, p-value = 0.03).
Pooled results of our meta-analysis and meta-regression show that exposure to PCSK9 inhibitors is not associated with an increased risk of neurocognitive adverse effects.
有研究表明降脂治疗会引起认知功能障碍。使用前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂与神经认知不良事件风险之间的关系尚不清楚。本荟萃分析旨在评估随机对照试验（RCT）中 PCSK9 抑制剂的神经认知安全性。
本研究按照系统评价和荟萃分析的首选报告项目（PRISMA）进行。通过 2019 年 9 月检索 PubMed（MEDLINE）、Embase 和 Cochrane 图书馆。入选标准包括：评估接受 Alirocumab、Evolocumab 或 Bococizumab 的参与者神经认知不良事件的 RCT，随访时间至少 6 个月。由两位独立评审员筛选检索结果。从纳入文献中提取安全性数据。使用随机效应荟萃分析汇总结果，在适用的情况下使用元回归分析。共纳入 21 项研究。在 59733 例患者中，31611 例接受 PCSK9 抑制剂治疗。随访时间从 24 周至 48 个月不等。两组间神经认知不良事件的发生率无显著差异（RR=1.01，95%CI：0.86-1.19，I²=3%）。每种药物的亚组分析也得出了相似的结果（alirocumab-RR=0.88，95%CI：0.72-1.08，I²=0%；evolocumab-RR=1.42，95%CI：0.74-2.73，I²=55%）。对 evolocumab 的元回归分析表明，研究持续时间延长与神经认知不良事件风险降低相关（β=-0.0037，p 值=0.03）。
本荟萃分析和元回归的汇总结果表明，暴露于 PCSK9 抑制剂与神经认知不良事件风险增加无关。
