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High On-Treatment Platelet Reactivity Determinants on Dual Antiplatelet Therapy in Patients With Ischemic Heart
E Z Golukhova1, Marina V Grigoryan, M N Ryabinina
1ФГБУ «Национальный медицинский исследовательский центр сердечно-сосудистой хирургии им. А. Н. Бакулева» Минздрава России. noemail@neicon.ru.
Insights
High on-treatment platelet reactivity (HOPR) during dual antiplatelet therapy (DAPT) is linked to body mass index (BMI) and soluble P-selectin levels. These factors, along with cholesterol and CYP2C19*2 allele, are key predictors of HOPR in patients with ischemic heart disease.
Area of Science:
- Cardiology
- Pharmacogenomics
- Clinical Chemistry
Background:
- Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is standard after percutaneous coronary intervention (PCI).
- High on-treatment platelet reactivity (HOPR) during DAPT is associated with increased risk of thrombotic events.
- Identifying factors influencing HOPR is crucial for optimizing antiplatelet therapy.
Purpose of the Study:
- To investigate the impact of laboratory and genetic factors on HOPR in patients undergoing PCI with DAPT.
- To identify predictors of HOPR in stable ischemic heart disease patients.
Main Methods:
- 94 patients with stable ischemic heart disease receiving DAPT post-PCI were studied.
- Platelet reactivity was assessed using light transmission aggregometry (LTA) and VerifyNow assay.
- Genotyping for CYP2C19 polymorphism and measurement of inflammatory markers (hsCRP, sP-selectin, IL-6, etc.) and lipid profiles were performed.
Main Results:
- HOPR incidence was 16% (LTA) and 24.5% (VerifyNow).
- Univariate analysis linked HOPR to higher BMI, total cholesterol, LDL cholesterol, sP-selectin, and von Willebrand factor activity.
- Carriage of the CYP2C19*2 allele was also associated with HOPR.
- Multivariate analysis identified BMI and sP-selectin as independent predictors of HOPR.
Conclusions:
- HOPR during DAPT is associated with elevated BMI, total and LDL cholesterol, CYP2C19*2 allele carriage, hsCRP, and sP-selectin levels.
- Body mass index and soluble P-selectin are independent predictors of HOPR, highlighting their clinical significance.
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=0.0l), low density lipoprotein CH (p=0.004), and sP-selectin (p=0.009), activity of von Willebrand factor (p=0.04). Carriage of CYP2C19*2 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 CYP2C19*2 allele, levels of hsCRP and sP-selectin. Independent factors significantly related to HORP were BMI and sP-selectin level.
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