Department of Neurology, University of California San Francisco, San Francisco, California, USA.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
Eur J Neurol. 2023 Jul;30(7):2112-2116. doi: 10.1111/ene.15820. Epub 2023 Apr 20.
Factor XI (FXI) is a promising therapeutic target for the prevention of thrombotic disease without increasing bleeding risk.
We performed Mendelian randomization (MR) analyses to investigate the association of genetically predicted reductions in FXI levels with risk of venous thromboembolism, ischemic stroke, bleeding outcomes, and lifespan.
Genetically predicted reductions in FXI levels were associated with lower risk of ischemic stroke (odds ratio per 1 standard deviation (SD) lower serum FXI 0.90, 95% confidence interval 0.87-0.93, p = 1.59 × 10 ), and venous thromboembolism (0.54, 0.49-0.59, p = 2.13 × 10 ) but did not associate with increased bleeding risk (p > 0.16). Genetically predicted reductions in serum FXI levels associated with longer lifespan (0.37 years per 1 SD lower serum FXI, 0.13-0.61, p = 0.003).
These genetic data support FXI as a potentially efficacious and safe therapeutic target and anticipate positive results from ongoing phase 3 clinical trials.
因子 XI（FXI）是预防血栓性疾病的有前途的治疗靶点，而不会增加出血风险。
我们进行了孟德尔随机化（MR）分析，以研究FXI 水平降低与静脉血栓栓塞、缺血性中风、出血结局和寿命的关联。
FXI 水平降低与缺血性中风（每降低 1 个标准差（SD）的血清 FXI 比值为 0.90，95%置信区间为 0.87-0.93，p=1.59×10 ）和静脉血栓栓塞（0.54，0.49-0.59，p=2.13×10 ）风险降低相关，但与出血风险增加无关（p>0.16）。血清 FXI 水平降低与寿命延长相关（每降低 1 个 SD 的血清 FXI 延长 0.37 年，0.13-0.61，p=0.003）。
这些遗传数据支持 FXI 作为一种潜在有效且安全的治疗靶点，并预计正在进行的 3 期临床试验将取得积极结果。
