High on-treatment platelet reactivity determinants on dual antiplatelet therapy in patients with ischemic heart disease before elective percutaneous coronary intervention

Abstract

Objective: to determine impact of different laboratory and genetic factors on high on-treatment platelet reactivity (HOPR) during dual antiplatelet therapy (DAPT). Methods. We included in this study 94 patients with stable ischemic heart disease (mean age 59±9.67 years). All patients underwent elective PCI with implantation of drug eluting stents at the background of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel. Platelet reactivity was assessed using light transmission aggregometry with 5 μmol / L ADP (LTA 5ADP) and VerifyNow assay before PCI. All patients underwent genotyping to detect CYP2C19 polymorphism. In 74 patients at baseline examination we determined levels of high-sensitivity C-reactive protein (hsCPR), soluble platelet-selectin (sP-selectin), soluble CD40-ligand (sCD40L), interleukin-6 (IL-6), plasminogen activator inhibitor (PAI-1) and activity of von Willebrand factor. Results. Incidence of HOPR according to LTA-5ADP was 16 % and VerifyNow-24.5 %. Univariate regression analysis showed that the following factors were significantly associated with HPR determined by LTA-5ADP: body mass index (BMI) (p=0.02), levels of total cholesterol (CH) (p=0.01), low density lipoprotein CH (p=0.004), and sP-selectin (p=0.009), activity of von Willebrand factor (p=0.04). Carriage of CYP2C192 allele was also associated with HOPR (p=0.006). According to multivariate regression analysis body mass index and level of sP-selectin were independent predictors of HOPR during DAPT. Conclusions. HOPR determined by LTA was significantly associated with high BMI, levels of total and LDL CH, carriage of CYP2C192 allele, levels of hsCRP and sP-selectin. Independent factors significantly related to HORP were BMI and sP-selectin level.