Sensitivity to clopidogrel and outcomes of long-term dual antiplatelet therapy in patients with multifocal atherosclerosis

Abstract

Introduction. Patients undergoing elective myocardial revascularization require 6 months of dual antiplatelet therapy (DAPT), including aspirin and clopidogrel. In patients with multifocal atherosclerotic lesion (MFA), it may be reasonable to extend the DAPT. Additional consideration of laboratory parameters, which reflect sensitivity to clopidogrel, may be useful in assessing the effectiveness and safety of prolongation DAPT.Aim. To determine the significance of laboratory parameters reflecting sensitivity to clopidogrel in assessing the prognosis of patients with MFA receiving long-term DAPT after myocardial revascularization.Materials and methods. 128 patients with coronary artery disease (CAD) and MFA were included from the prospective register of antithrombotic therapy (REGATTA-1), ClinicalTrials NCT04347200. Inclusion criteria were elective myocardial revascularization, the use of DAPT planned for at least one year and additional determination sensitivity to clopidogrel – residual platelet reactivity and polymorphisms of the CYP2C19* gene. Thrombotic events (TO) in any vascular beds and hemorrhagic complications(GO) (BARC 2–5).Results. The median of DAPT was 380 days, IQR (346. 447). The total incidence of thrombotic events and hemorrhagic complications (the majority – BARC 2) were 9.9 and 4.4 cases per 100 patient-years. The frequency of bleeding events was 4.4 cases per 100 patient-years. There was no association of TO with the PRU and pharmacogenetic parameters. CYP2C19*17 allele carriers tended to have a higher frequency of GO rates compared compared to wild genotype carriers (63% versus 29%, p = 0.05). The frequency of GO in patients with PRU 147 (two lower quintiles) was higher compared with the frequency of GO in the three upper quintiles of the distribution: 12% vs. 3%, p = 0.041. PRU lost significance in multivariate analysis and an independent laboratory predictor of GO was the carriage of CYP2C19*17 alleles (HR 4.8).Conclusion. In patients with MFA who are candidates for long-term DATT after myocardial revascularization, an additional pharmacogenetic assessment of the effect of clopidogrel (allelic variants of CYP2C19*17) can be discussed in order to predict bleeding

Keywords

• residual platelet reactivity
• bleeding
• cyp2c19 gene polymorphism
• elective myocardial revascularization