Ticagrelor for CYP2C19 loss-of-function carriers undergoing intracranial aneurysm stenting

Objectives 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.