scholarly journals Impact of CYP2C19 Polymorphism on Platelet Function Tests and Coagulation and Inflammatory Biomarkers in Patients Undergoing Percutaneous Coronary Intervention

Author(s):  
Koichi Kaikita ◽  
Takamichi Ono ◽  
Satomi Iwashita ◽  
Naoki Nakayama ◽  
Koji Sato ◽  
...  
2021 ◽  
Author(s):  
Yang Zhang ◽  
Rui Peng ◽  
Xiaojuan Li ◽  
Gaowa Cheng ◽  
Ximing Wang ◽  
...  

Abstract Background: Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated.Methods: Patients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2–3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer.Results: The final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 µM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P < 0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P < 0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701–0.875, P < 0.001) in receiver-operating characteristic curve analysis.Conclusions: Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Zhang ◽  
Rui Peng ◽  
Xiaojuan Li ◽  
Gaowa Cheng ◽  
Ximing Wang ◽  
...  

Abstract Background Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routine index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated. Methods Patients receiving dual antiplatelet therapy (DAPT) were scheduled for the assessment of platelet reactivity at 2–3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP)-FCM assay, were applied in the evaluation of platelet reactivity. The MPV was measured simultaneously with EDTA plasma using a Sysmex XN 2000 automated hematology analyzer. Results The final study population included the aspirin + clopidogrel group (n = 46) and the aspirin + ticagrelor group (n = 66). In the aspirin + ticagrelor group, the maximal light transmittance (LT) changes in response to 5 μM ADP assessed by LTA was obviously lower than that in the aspirin + clopidogrel group (P <  0.001). The platelet reactivity index (PRI) level in the VASP test was also markedly lower in the group given aspirin and ticagrelor (P <  0.001). There was a significant difference in HPR between the two groups. MPV showed a potent ability to predict the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701–0.875, P <  0.001) in receiver-operating characteristic curve analysis. Conclusions Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority in suppressing platelet function and a lower HPR rate. In addition, there existed a significant independent association between MPV and high prevalence of HPR in the VASP assay.


2020 ◽  
Author(s):  
Yang Zhang ◽  
Rui Peng ◽  
Xiaojuan Li ◽  
Gaowa Cheng ◽  
Ximing Wang ◽  
...  

Abstract Background: Knowledge on the pharmacodynamic effects of antiplatelet drugs including clopidogrel and ticagrelor on Asian patients is scarce. We aim to evaluate the effects of the two drugs on platelet reactivity in the treatment of Chinese patients who underwent percutaneous coronary intervention (PCI), using two platelet function tests (PFT). Meanwhile, the relationship between mean platelet volume (MPV), a routinely index of platelet size, and high on-treatment platelet reactivity (HPR) is also investigated.Methods: Patients receiving dual antiplatelet therapy (DAPT) treatment were scheduled for the assessment of platelet reactivity at 2-3 days after PCI. Two PFTs, light transmission aggregometry (LTA) and vasodilator-stimulated phosphoprotein (VASP) assay, were applied in the evaluation of platelet reactivity. MPV was measured simultaneously.Results: The final study population included the traditional therapy group with aspirin and clopidogrel (n = 46) and the new therapy group with aspirin and ticagrelor (n = 66). In the new therapy group, the value of platelet aggregation assessed by LTA was obviously lower than that in the traditional therapy group (P < 0.001). The platelet reactivity index (PRI) level at VASP test was also markedly lower in the group given the new therapy (P < 0.001). It presented significant difference of HPR rates between the two groups. MPV showed a potent ability in predicting the presence of HPR at VASP assay (AUC = 0.788, 95% CI: 0.701-0.875, P < 0.001) in receiver-operating characteristic curve analysis.Conclusions: Compared with clopidogrel, ticagrelor has dramatically greater antiplatelet effect, with a superiority of suppressing platelet function and a lower HPR rates. In addition, there existed a significantly independent association between MPV and high prevalence of HPR at VASP assay.


2021 ◽  
Vol 10 (17) ◽  
pp. 3992
Author(s):  
Renske H. Olie ◽  
Rachelle R. K. Hensgens ◽  
Petal A. H. M. Wijnen ◽  
Leo F. Veenstra ◽  
Bianca T. A. de Greef ◽  
...  

On-treatment platelet reactivity in clopidogrel-treated patients can be measured with several platelet function tests (PFTs). However, the agreement between different PFTs is only slight to moderate. Polymorphisms of the CYP2C19 gene have an impact on the metabolization of clopidogrel and, thereby, have an impact on on-treatment platelet reactivity. The aim of the current study is to evaluate the differential effects of the CYP2C19 genotype on three different PFTs. Methods: From a prospective cohort study, we included patients treated with clopidogrel following percutaneous coronary intervention (PCI). One month after PCI, we simultaneously performed three different PFTs; light transmission aggregometry (LTA), VerifyNow P2Y12, and Multiplate. In whole EDTA blood, genotyping of the CYP2C19 polymorphisms was performed. Results: We included 308 patients treated with clopidogrel in combination with aspirin (69.5%) and/or anticoagulants (33.8%) and, based on CYP2C19 genotyping, classified them as either extensive (36.4%), rapid (34.7%), intermediate (26.0%), or poor metabolizers (2.9%). On-treatment platelet reactivity as measured by LTA and VerifyNow is significantly affected by CYP2C19 metabolizer status (p < 0.01); as metabolizer status changes from rapid, via extensive and intermediate, to poor, the mean platelet reactivity increases accordingly (p < 0.01). On the contrary, for Multiplate, no such ordering of metabolizer groups was found (p = 0.10). Conclusions: For VerifyNow and LTA, the on-treatment platelet reactivity in clopidogrel-treated patients correlates well with the underlying CYP2C19 polymorphism. For Multiplate, no major effect of genetic background could be shown, and effects of other (patient-related) variables prevail. Thus, besides differences in test principles and the influence of patient-related factors, the disagreement between PFTs is partly explained by differential effects of the CYP2C19 genotype.


2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Akintunde M Akinjero ◽  
Oluwole Adegbala ◽  
Esosa Edo-Osagie ◽  
Nike Akinjero ◽  
Tomi Akinyemiju

Background: The need to balance bleeding and clotting risks after percutaneous coronary intervention (PCI) has led to interest in platelet function monitoring as a strategy to improve post-PCI outcomes. The prognostic value of platelet function testing in monitoring response to antiplatelet therapy after PCI remains unclear. Prior studies have been inconclusive. We sought to conduct an updated meta-analysis to address this gap in knowledge. Methods: We conducted a systematic search of EMBASE, PUBMED and the Cochrane libraries for studies since inception to December 2016 on platelet function monitoring. Our search yielded 203 studies, out of which 83 were extracted for full-text review. Only 3 studies met inclusion criteria. We pooled odds ratios using random-effects statistics, Mantel-Haenszel method. I2 and Chi- squared statistic was used to evaluate for heterogeneity. Publication bias was assessed using the funnel plot. Primary outcome was major adverse cardiovascular events (MACE). This was defined in the studies as a composite of cardiovascular death, myocardial infarction, stroke, stent thrombosis, and bleeding complications. Results: The 3 randomized controlled trials that were analyzed involved 3701 patients. There were 550 MACE (29.76%) in the platelet function monitored group compared with 514 (27.74%) in the control. MACE (Figure 1) was not significantly higher for the platelet function monitored group during follow-up compared with control (pooled Odds Ratio:1.11 [95% CI: 0.96-1.28], p = 0.15). Tests for heterogeneity were not significant, with I2 of 0%, Chi2 = 1.52 (p = 0.47); and small study bias was absent on visual inspection of the funnel plot. Conclusions: Platelet function monitoring continues to be used in practice. Results from this meta-analysis show no benefit of platelet function monitoring compared with conventional strategy with regards to MACE after PCI. Future research is needed to further evaluate this finding.


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