Cytochrome СYP2C19 gene polymorphisms and bleeding in patients treated with clopidogrel as part of dual antithrombotic therapy after acute coronary syndrome

Relevance. The advantages of using clopidogrel for the treatment of atherosclerotic cardiovascular diseases have been demonstrated in many studies. However, the risk of clinically significant bleeding is increased when clopidogrel is used in combination with other drugs.

Objective. To investigate the possible relationship between the carriage of CYP2C19 loss-of-function and gain-of-function alleles and bleeding events in patients with coronary heart disease (CHD) ± atrial fibrillation (AF) receiving dual antithrombotic therapy with clopidogrel after acute coronary syndrome (ACS).

Materials and methods. A total of 150 patients (median age 65 [60,75;73] years) were studied, including 77 patients with CHD without AF taking clopidogrel + acetylsalicylic acid; and 73 patients with CHD and AF taking clopidogrel + rivaroxaban or apixaban. DNA samples obtained from all patients were genotyped for CYP2C19 rs4244285, rs4986893, and rs12248560. The follow-up period was 16 weeks ± 1 days. Information about bleeding events was obtained using the MCMDM-1 questionnaire.

Results. Bleeding occurred in 26 (17.3%) patients. The most common bleeding events were nosebleeds (42.3%), bruises (30.8%), and oral bleeding (26.9%). Among patients with bleeding events compared with those who did not, carriers of the rs12248560 (CYP2C19*17) TT genotype were significantly more common — 19.2% and 3.2%, respectively (p = 0.008). A similar result was obtained in the CHD group without AF (21.4% vs. 3.2%, respectively, p = 0.039). Among patients in the presence of bleeding, ultrarapid metabolizers (*17/*17) were administered significantly more frequently than those without bleeding (p=0.008).

Conclusion. Carriage of the rs12248560 (*17) TT genotype and ultrarapid metabolizers (*17/*17) phenotype were associated with hemorrhagic events in patients with ACS receiving dual antithrombotic therapy with clopidogrel.

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