Abstract
Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel administered to treat patients with acute coronary syndrome (ACS) is still being used. However, despite the proven efficacy of this treatment regimen, thromboembolic complications have been observed in some individuals. The reason for this phenomenon is linked to the so-called increased responsiveness of platelets despite high platelet resistance (HPR). A significant role in HPR is attributed to genetically determined differences in the absorption and activation of clopidogrel. The aim of the study was to assess the incidence of polymorphisms of the ABCB1 and CYPC19 genes that encode proteins involved in the absorption and metabolism of clopidogrel. The analysis was performed in 199 consecutive patients from Lower Silesian voivodeship (Poland) who underwent coronary angioplasty with stenting for ACS. The single nucleotide polymorphism of the CYP2C19 and ABCB1 genes was performed using a mini sequencing or restriction fragment length polymorphism method. The results of this study revealed the high incidence of patients who may be unresponsive to antiplatelet treatment due to genetic causes. The CYPC19*2 allele in the form of homozygote or mutation heterozygote appeared in 26.1% of the study population. ABCB1 (C3435C> T) polymorphism was associated with 84% of patients. The total incidence of allelic disorders of low drug absorption and metabolism reached 14.6%. The data obtained should prompt clinicians to use more recent antiplatelet agents (ticagrelor or prasugrel) first, instead of clopidogrel.
Highlights
The results of this study revealed the high incidence of patients who may be unresponsive to antiplatelet treatment due to genetic causes
ABCB1 (C3435C> T) polymorphism was associated with 84% of patients
Dual antiplatel therapy (DAPT) with aspirin and clopidogrel has until recently been the gold standard for the treatment of acute coronary syndrome (ACS) patients
Summary
Dual antiplatel therapy (DAPT) with aspirin and clopidogrel has until recently been the gold standard for the treatment of acute coronary syndrome (ACS) patients. Despite the proven efficacy of this treatment regimen, thromboembolic complications continue to be observed in some patients.[1,2] The reason for this phenomenon is associated with a so-called sustained increase in platelets activity, in spite of DAPT. This phenomenon may be due to an impaired aspirin response, but it is mainly associated with an ineffective treatment with clopidogrel. Spot mutations in the ABCB1 gene type C3435C> T, resulting in the emergence of mutation homozygotes (TT) or mutation heterozygotes (CT) in place of proper homozygotes (CC), imply (TT) increased P-GP activity This activity causes an excessive rejection of clopidogrel, hindering its attainment of adequate plasma concentrations. A significant role in HPR is attributed to genetically determined differences in the absorption and activation of clopidogrel
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