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

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.