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Ticagrelor for CYP2C19 loss-of-function carriers undergoing intracranial aneurysm stenting
Yangyang Zhou1,2, Qichen Peng2, JinBiao Yao2
1Department of Neurosurgery, Beijing Tiantan Hospital, Beijing, China.
Insights
For patients undergoing intracranial aneurysm stenting, CYP2C19 loss-of-function (LOF) carriers using clopidogrel face higher ischemic event risks. Switching to ticagrelor significantly reduces these risks without increasing bleeding.
Area of Science:
- Cardiovascular Medicine
- Pharmacogenomics
- Neurosurgery
Background:
- CYP2C19 loss-of-function (LOF) alleles impact clopidogrel efficacy.
- Patients with unruptured intracranial aneurysms (IAs) undergoing endovascular treatment require antiplatelet therapy.
- Genetic variations can influence drug response and patient outcomes.
Purpose of the Study:
- To assess if substituting ticagrelor for clopidogrel in CYP2C19 LOF carriers reduces perioperative ischemic events after IA endovascular treatment.
- To evaluate the safety of ticagrelor versus clopidogrel in this patient population regarding bleeding events.
Main Methods:
- A retrospective cohort study included 654 patients treated for unruptured IAs.
- Patients were stratified by CYP2C19 genotype (LOF vs. non-LOF) and P2Y12 antagonist (clopidogrel or ticagrelor).
- Primary endpoint: 30-day postoperative ischemic events. Safety endpoint: 30-day postoperative bleeding events.
Main Results:
- LOF carriers using clopidogrel had a significantly higher risk of ischemic events (7.8%) compared to the non-LOF group (3.3%).
- Switching to ticagrelor in LOF carriers reduced ischemic event incidence to 1.9%, significantly lower than clopidogrel use (P=0.032).
- No significant difference in bleeding events was observed between the clopidogrel and ticagrelor groups in LOF carriers (2.9% vs. 1.3%, P=0.377).
- Independent risk factors for ischemic events included increasing age, non-saccular aneurysms, and clopidogrel use in LOF carriers.
Conclusions:
- CYP2C19 LOF alleles are associated with increased ischemic risk after IA stenting.
- A ticagrelor-based strategy for LOF carriers effectively mitigates perioperative ischemic event risk.
- This alternative strategy does not elevate the risk of perioperative bleeding events.
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.
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