The frequencies of CYP2C19*2, *3, and *17 alleles and their impact on the clinical efficacy of doubled maintenance dose of clopidogrel in Syrian patients with coronary artery disease.

Background: Genetic variations in the CYP2C19 gene, which encodes the major enzyme responsible for activating clopidogrel, may influence response to Clopidogrel antiplatelet therapy. This study aimed to assess the prevalence of CYP2C19 variants in Syrian patients with coronary artery disease (CAD) and evaluate the impact of these variants on the clinical efficacy of a doubled maintenance dose of clopidogrel following percutaneous coronary intervention (PCI).

Methods: This study included 50 Syrian CAD patients on dual antiplatelet therapy (DAPT) with a doubled maintenance dose of clopidogrel. CYP2C19 genotypes were determined by PCR, followed by Sanger sequencing. Clinical outcomes, including major acute cardiovascular events (MACE) and bleeding events, were monitored over 18-24 months.

Results: The allele frequencies were 8% for CYP2C19*2, 0% for CYP2C19*3, and 17% for CYP2C19*17. The distribution of our study population by CYP2C19 genotype-predicted metabolizer phenotypes was 56% for normal metabolizers (NMs), 26% for intermediate metabolizers (IMs), 12% for rapid metabolizers (RMs), and 2% for ultra-rapid metabolizers (UMs). No association was found between the CYP2C19*2 allele and recurrent ischemic events or between the CYP2C19*17 allele and bleeding complications in patients treated with a doubled maintenance dose of clopidogrel.

Conclusions: In Syrian patients undergoing PCI, a doubled maintenance dose of clopidogrel (150 mg/day) may help mitigate variability in response due to CYP2C19*2 carrier status, offering potential benefits in optimizing antiplatelet therapy. However, given the study's limited sample size, these findings should be interpreted with caution, and larger studies are needed to confirm this potential benefit.