Ticagrelor for CYP2C19 loss-of-function carriers undergoing intracranial aneurysm stenting
Yangyang Zhou, Qichen Peng, JinBiao Yao, ShengQi Hu, Xuanping Xie, Xiaoxi Zhu, Kaiyu Liu, Wenqiang Li, Shiqing MuObjectives
This study aimed to evaluate whether replacing clopidogrel with ticagrelor in CYP2C19 loss-of-function (LOF) carriers can reduce the incidence of perioperative ischemic events in endovascular treatment for unruptured intracranial aneurysms (IAs).
Methods
A retrospective cohort of 654 patients was divided into three groups based on their CYP2C19 genotype and P2Y12 antagonist regimen: the non-LOF group (n=240, using clopidogrel), the LOF-Clopidogrel group (n=309, using clopidogrel), and the LOF-Ticagrelor group (n=105, using ticagrelor). The primary endpoint was ischemic events within 30 days postoperatively, and the safety endpoint was bleeding events within 30 days postoperatively.
Results
Compared with the non-LOF group (3.3%), the risk of ischemic events was significantly higher in the LOF-Clopidogrel group (7.8%; OR 2.442, 95% CI 1.072 to 5.248, P=0.028). For LOF carriers, after replacing clopidogrel with ticagrelor, the incidence of ischemic events decreased to 1.9%, which was lower than that of the LOF-Clopidogrel group (1.9% vs 7.8%; OR 0.231, 95% CI 0.053 to 0.866, P=0.032), and there was no significant difference between the two groups in the overall incidence of bleeding (2.9% vs 1.3%, P=0.377). Increasing age (OR 1.043, P=0.028), non-saccular aneurysm (OR 3.196, P=0.012), and clopidogrel use in LOF carriers (OR 2.437, P=0.035) were independent risk factors for ischemic events.
Conclusions
CYP2C19 LOF alleles significantly increase ischemic risks following IA stenting. Implementing a ticagrelor alternative strategy for LOF carriers can significantly reduce the risk of ischemic events without increasing the risk of perioperative bleeding events.