An exploratory study on clopidogrel dosage in sICAS patients with CYP2C19 loss-of-function alleles under rapid detection

Objective To investigate the effectiveness and safety of dual antiplatelet therapy with different doses of clopidogrel combined with aspirin in symptomatic intracranial atherosclerotic stenosis (sICAS) patients with CYP2C19 loss-of-function alleles.Methods The subjects were selected from sICAS patients who were admitted to Xuzhou Central Hospital from February 2022 to September 2022 for immediate buccal mucosal sampling and CYP2C19 genotype testing. The CYP2C19 * 2 and/or CYP2C19 * 3 (CYP2C19 loss-of-function alleles) carriers were screened, where patients carrying one loss-of-function allele were CYP2C19 medium metabolic type, and those with two loss-of-function alleles were CYP2C19 slow metabolic type. These patients carrying loss-of-function alleles were randomly divided into two groups:a standard treatment group (75 mg/d clopidogrel) and an enhanced treatment group (150 mg/d clopidogrel). All the patients were treated with aspirin at 100 mg once a day and received dual antiplatelet therapy for 90 days. Then, their general baseline data were collected for effectiveness evaluation. The degree of neurological deficits and prognosis before and after antiplatelet therapy was evaluated by the National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS).Results There was no statistical difference in NIHSS scores between the standard treatment group and the enhanced treatment group after treatment for 7 and 21 days (P>0.05). The enhanced treatment group showed lower NIHSS scores than the standard treatment group after treatment for 90 days (P<0.01). Multivariate logistic regression analysis suggested that NIHSS score at admission and low-density lipoprotein cholesterol (LDL-C) were the independent risk factors for poor clinical prognosis. Compared with the standard dose of clopidogrel combined with aspirin, the combination of the enhanced-dose clopidogrel and aspirin did not increase the bleeding risk of sICAS patients after treatment for 90 days (P>0.05), but did not effectively reduce the recurrence rate of stroke after 90 days (P>0.05).Conclusions For sICAS patients carrying CYP2C19 loss-of-function alleles, the enhanced-dose clopidogrel and aspirin therapy can better improve the symptoms of neurological deficits 90 days after onset, compared with the standard-dose clopidogrel and aspirin therapy, and does not increase the incidence of adverse events such as bleeding conversion. However, it does not effectively reduce the recurrence rate of stroke 90 days after onset.