scholarly journals Impact of selected genetic factors on clopidogrel inactive metabolite level and antiplatelet response in patients after percutaneous coronary intervention

2020 ◽  
Author(s):  
Urszula Adamiak-Giera ◽  
Anna Czerkawska ◽  
Szymon Olędzki ◽  
Mateusz Kurzawski ◽  
Krzysztof Safranow ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Bleeding Risk ◽  
Metabolite Level ◽  
Coronary Syndrome ◽  
Inhibition Of Platelet Aggregation ◽  
Percutaneous Coronary ◽  
Inactive Metabolite ◽  
Before And After ◽  
Clopidogrel Therapy

Abstract Background and objective Clopidogrel is frequently used as part of optimal dual antiplatelet therapy in high-bleeding risk patients with the acute coronary syndrome. The concentration of the inactive carboxylic acid metabolite of clopidogrel might be useful to evaluate the response to clopidogrel therapy. Therefore, we sought to correlate the inhibition of platelet aggregation with the plasma level of the inactive metabolite of clopidogrel in patients after percutaneous coronary interventions (PCI) and their associations with the most frequently studied genetic polymorphisms. For this purpose, the fast and simple HPLC method for determining the concentration of the inactive metabolite was developed. Methods The effect of CYP2C19, CYP3A4/5, ABCB1 and PON1 genes on the plasma inactive metabolite concentration of clopidogrel and the platelet aggregation was investigated in 155 patients before and after PCI. Results The concentration of the inactive metabolite of clopidogrel was not significantly different in the intermediate metabolizers (IM) of CYP2C19 compared with extensive metabolizers (EM) both before and after PCI, while inhibition of platelet aggregation was found to be significantly better in EM than in IM. The presence of the A allele at position 2677 in the ABCB1 gene was associated with a significantly lower concentration of inactive metabolite of clopidogrel before PCI. Conclusion The CYP2C19*2 allele was associated with decreased platelet reactivity during clopidogrel therapy before and after PCI. Simultaneous determination of platelet aggregation and concentration of the inactive clopidogrel metabolite may be useful in clinical practice to find the cause of adverse effects or insufficient treatment effect in patients chronically treated with clopidogrel.

Chewing versus Swallowing Ticagrelor to Accelerate Platelet Inhibition in Acute Coronary Syndrome - the CHEERS study

2017 ◽  
Vol 117 (04) ◽  
pp. 727-733 ◽  
Author(s):  
Moshe Katz ◽  
Ehud Regev ◽  
Avi Sabbag ◽  
Israel Mazin ◽  
Arsalan Abu-Much ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Metabolic Activation ◽  
Platelet Inhibition ◽  
Standard Group ◽  
Loading Dose ◽  
Study Objective ◽  
Coronary Syndrome ◽  
Inhibition Of Platelet Aggregation ◽  
To Receive

SummaryIt was the study objective to evaluate whether chewing a 180 mg loading dose of ticagrelor versus an equal dose of traditional oral administration, enhances inhibition of platelet aggregation 1 hour (h) after administering a ticagrelor loading dose in non-ST elevation myocardial infarction (NSTEMI) patients. Dual anti-platelet therapy represents standard care for treating NSTEMI patients. Ticagrelor is a direct acting P2Y12 inhibitor and, unlike clopidogrel and prasugrel, does not require metabolic activation. Fifty NSTEMI patients were randomised to receive either a chewing loading dose of 180 mg ticagrelor or an equal standard oral dose of ticagrelor. Platelet reactivity was evaluated by VerifyNow at baseline, 1 and 4 h post-loading dose. Results are reported in P2Y12 reaction units. Patients then continued to receive standard 90 mg oral ticagrelor twice daily. Baseline characteristics did not differ between the two groups. P2Y12 reaction units in the chewing group compared with the standard group at 0, 1 and 4 h after ticagrelor loading dose were: 245 vs 239 (p=0.59), 45 vs 130 (p=0.001) and 39 vs 60 (p=0.12), respectively, corresponding to a relative inhibition of platelet aggregation of 83 % vs only 47 % at 1 h (p< 0.001), and 84 % vs 77 % (p=0.59) at 4 h. Major adverse cardiac and cardiovascular events at 30 days were low (2 %), occurring in only one patient in the standard group. In conclusion, chewing a 180 mg ticagrelor loading dose is feasible and facilitates both faster and improved early inhibition of platelet aggregation in NSTEMI patients, compared with a standard oral-loading dose.Supplementary Material to this article is available online at www.thrombosis-online.com.

Decrease in high on-treatment platelet reactivity (HPR) prevalence on switching from clopidogrel to prasugrel: Insights from the switching anti-platelet (SWAP) study

2013 ◽  
Vol 109 (02) ◽  
pp. 347-355 ◽  
Author(s):  
Dominick Angiolillo ◽  
Roger DeRaad ◽  
Andrew Frelinger ◽  
Paul Gurbel ◽  
Timothy Costigan ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Cytochrome P450 ◽  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Maintenance Phase ◽  
Reactivity Index ◽  
Loading Dose ◽  
Cyp2c19 Genotype ◽  
Coronary Syndrome ◽  
Clopidogrel Therapy

SummaryThe prevalence of high platelet reactivity (HPR) in patients who have switched from clopidogrel to prasugrel during maintenance phase after an acute coronary syndrome (ACS) event is unknown. Therefore, the effect of switching from clopidogrel to prasugrel on the prevalence of HPR was evaluated. This analysis from the previously reported SWAP (SWitching Anti Platelet) study assessed HPR at baseline, 2 and 24 hours, and seven days after switching from clopidogrel to prasugrel maintenance dose (MD), with or without a prasugrel loading dose (LD) using four definitions: maximum platelet aggregation (MPA) >65% (primary endpoint), MPA >50%, P2Y12 reaction units (PRU) >235, and platelet reactivity index (PRI) ≥50%. A total of 95 patients were available for analysis; 56 patients provided DNA for genetic assessments of cytochrome P450 (CYP) 2C19. There were 26 (27.4%) patients with HPR at the end of the clopidogrel run-in (defined as MPA >65%). The HPR prevalence varied by each definition and ranged from 19% (PRU >235) to 68% (PRI ≥50%). A significantly higher HPR prevalence was observed during clopidogrel versus the combined prasugrel therapy groups at seven days as measured by MPA >65% (21.2% vs. 4.5%, p>0.05), PRU >235 (18.8% vs. 0%, p=0.001), and PRI ≥50% (66.7% vs. 7.9%, p<0.0001). There was a significantly higher percentage of subjects carrying at least one reduced function allele with HPR measured by MPA >65% (p=0.02) or PRU >235 (p=0.05) than non-carriers with HPR. Switching ACS patients during maintenance clopidogrel therapy to prasugrel with or without an LD is associated with a reduced HPR prevalence and may provide an alternative strategy to treat patients with HPR, independent of CYP2C19 genotype.

P329Residual platelet reactivity after pre-treatment with ticagrelor prior to primary percutaneous coronary intervention is associated with suboptimal myocardial reperfusion

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Roule ◽  
T Heudel ◽  
A Lemaitre ◽  
M Bignon ◽  
P Ardouin ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
Myocardial Reperfusion ◽  
Primary Pci ◽  
Inhibition Of Platelet Aggregation ◽  
Percutaneous Coronary ◽  
Pre Treatment ◽  
Verify Now

Abstract Background The evidence of a clinical benefit of P2Y12 inhibitor pre-treatment in primary percutaneous coronary intervention (PCI) and the relation between the level of platelet inhibition and myocardial reperfusion with newer potent P2Y12 inhibitors remain unclear. Objectives We aimed to assess the relationship between platelet reactivity at the time of primary PCI after pre-treatment with aspirin and ticagrelor and the post-PCI myocardial blush grade (MBG). Methods We prospectively included 61 patients. Platelet reaction units for ticagrelor (PRU) and aspirin reaction units (ARU) were measured using the point-of-care test VerifyNow before PCI. The high on-ticagrelor (PRU >208) and on-aspirin (ARU ≥550) platelet reactivity (HPR and HaPR) were assessed. Patients were divided into two groups according to MBG 3 or <3. Results MBG 3 was identified in 28 (46%) patients. Mean PRU was lower in such patients as compared to those with MBG <3 (155.82±90.91 vs 227.42±65.18; p=0.001) while mean ARU was similar between groups. HPR and HaPR were observed in 30 (49.2%) and 11 patients (18%), respectively. HPR but not HaPR was more frequent in the group with impaired MBG (66.7 vs 28.6%; p=0.003 and 21.2 vs 14.3%; p=0.48 respectively). Table 1. Platelet reactivity results Verify Now at admission All Final Blush <3 Final Blush 3 p n=61 (100%) n=33 (54%) n=28 (46%) PRU P2Y12 194.56±85.32 227.42±65.18 155.82±90.91 0.001 Base 193.54±49.01 194.79±45.68 192.07±53.48 0.83 Inhibition of platelet aggregation (%) 15.61±29.85 5.7±17.55 27.29±36.79 0.007 ARU 463.97±76.45 472.58±72.5 453.82±81 0.34 PRU >208 30 (49.1%) 22 (66.7%) 8 (28.6%) 0.003 ARU ≥550 11 (18%) 7 (21.2%) 4 (14.3%) 0.48 Verify Now at day 1 n=57 n=30 n=27 p PRU P2Y12 40.86±41.43 47.27±45.87 33.74±35.35 0.21 Base 196.98±36.19 193.67±30.67 200.81±41.97 0.47 Inhibition of platelet aggregation (%) 79.8±17.96 76.37±20.54 83.77±13.78 0.11 ARU = Aspirin reaction units; PRU = P2Y12 reaction units. Conclusion In conclusion, our study shows that higher PRU and the subsequent HPR at the time of primary PCI, after pretreatment with ticagrelor, are the only correlates of post PCI MBG. These findings support the earliest possible loading with ticagrelor prior to primary PCI. Acknowledgement/Funding The study was supported by grants from Terumo. The funder has no role in any step of the study.

scholarly journals Multiple Mutations of CYP2C19, PON1 and ABCB1 Influence Platelet Response, Bleeding and Thrombosis Risk to Clopidogrel after Percutaneous Coronary Intervention: A Retrospective Study

2021 ◽  
Author(s):  
Hui Jin ◽  
Jinfei Song ◽  
Xiaoying Shen ◽  
Qing Liang ◽  
Guangchun Sun ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Platelet Aggregation ◽  
Platelet Reactivity ◽  
Bleeding Risk ◽  
Coronary Intervention ◽  
Genetic Mutation ◽  
Platelet Response ◽  
Chinese Han ◽  
Thrombosis Risk ◽  
Percutaneous Coronary

Abstract Background:Different combinations of multiple mutations of CYP2C19, PON1and ABCB1 for the efficiency and safety of Clopidogrel in patients undergoing percutaneous coronary intervention (PCI) remain unclear.Methods: 263 Chinese Han patients receiving 75mg Clopidogrel and 100mg Aspirin every day for 12 months after PCI were enrolled in this study. ADP-induced platelet aggregation rates, thrombosis and bleeding risk are used to compare the Clopidogrel response among the combined genetic mutation. Results: Our study demonstrated that multiple genetic mutations are very common in patients receiving Clopidogrel and Aspirin after PCI.Patients who have high ADP-induced platelet aggregation rate with more mutations of CYP2C19, PON1 and ABCB1. Patients with full mutations of CYP2C19, PON1 and ABCB1 have highest risk of thrombosis and lowest risk of bleeding in patients receiving clopidogrel and aspirin with one-year follow-up duration.Conclusions:We summarized multiple genetic polymorphism influences platelet reactivity, bleeding and thrombosis risk to Clopidogrel after percutaneous coronary intervention.

scholarly journals Relation of Functional Activity of Platelets to Prognosis of Unfavorable Cardiovascular Events in Patients with Acute Coronary Syndrome. Results of a Registry Study

Kardiologiia ◽  
2019 ◽  
Vol 59 (10) ◽  
pp. 5-13
Author(s):  
N. V. Lomakin ◽  
L. I. Buryachkovskaya ◽  
A. B. Sumarokov ◽  
Z. A. Gabbasov ◽  
A. N. Gerasimov
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Coronary Syndrome ◽  
Platelet Aggregation ◽  
Kidney Disease ◽  
Functional Activity ◽  
Cardiovascular Events ◽  
Platelet Reactivity ◽  
Coronary Syndrome ◽  
C Statistic

Aim: to assess relation ofhigh functional activity ofplatelets to prognosis ofunfavorable cardiovascular events in patients with Acute Coronary Syndrome (ACS).Materials. The study was based on the data of a single center ACS registry conducted in the Central Clinical Hospital of the Presidential Affairs Department of Russian Federation. Of 529 included patients in 425 without contraindications to double antiplatelet therapy we carried out analysis of dependence of 30 days level of unfavorable events on parameters of functional activity of platelets.Results. High on-treatment platelet reactivity (HTPR) was found to be associated with 3.5 increase of mortality in the group of patients with high cardiovascular risk. Logistic model of prognosis of unfavorable events based on multifactorial analysis of data from patients with measured platelet aggregation included chronic kidney disease, type of myocardial infarction, and degree ofplatelet aggregation >45%. C -statistic was equal to 0.77. We also present in this paper discussion of problems related to studying approaches to individualization of anti-aggregation therapy in real clinical practice and problems of organization ofsimilar studies.Conclusion. The study showed that patients with ACS increased platelet aggregation, as well as chronic kidney disease and type 2 MI are associated with a 30 day prognosis of adverse events.

scholarly journals Does Baseline On-treatment Platelet Reactivity Impact Long-term Prognosis in Patients with Acute Coronary Syndrome and Thrombocytopenia Who Underwent Percutaneous Coronary Intervention?

2021 ◽  
Author(s):  
Ru Liu ◽  
Tianyu Li ◽  
Deshan Yuan ◽  
Yan Chen ◽  
Xiaofang Tang ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Acute Coronary Syndrome ◽  
Real World ◽  
Cox Regression ◽  
Platelet Reactivity ◽  
Coronary Intervention ◽  
The Real ◽  
Coronary Syndrome ◽  
Percutaneous Coronary

Abstract Objectives: This study analyzed the association between on-treatment platelet reactivity and long-term outcomes of patients with acute coronary syndrome (ACS) and thrombocytopenia (TP) in the real world. Methods: A total of 10724 consecutive cases with coronary artery disease who underwent percutaneous coronary intervention (PCI) were collected from January to December 2013. Cases with ACS and TP under dual anti-platelet therapy were enrolled from the total cohort. 5-year clinical outcomes were evaluated among cases with high on-treatment platelet reactivity (HTPR), low on-treatment platelet reactivity (LTPR) and normal on-treatment platelet reactivity (NTPR), tested by thromboelastogram (TEG) at baseline. Results: Cases with HTPR, LTPR and NTPR accounted for 26.2%, 34.4% and 39.5%, respectively. Cases with HTPR were presented with the most male sex, lowest hemoglobin level, highest erythrocyte sedimentation rate and most LM or three-vessel disease, compared with the other two groups. The rates of 5-year all-cause death, major adverse cardiovascular and cerebrovascular events (MACCE), cardiac death, myocardial infarction (MI), revascularization, stroke and bleeding were all not significantly different among three groups. Multivariable Cox regression indicated that, compared with cases with NTPR, cases with HTPR were not independently associated with all endpoints, as well as cases with LTPR (all P>0.05). Conclusions: In patients with ACS and TP undergoing PCI, 5-year all-cause death, MACCE, MI, revascularization, stroke and bleeding risk were all similar between cases with HTPR and cases with NTPR, tested by TEG at baseline, in the real world. The comparison result was the same between cases with LTPR and NTPR.

Sign in / Sign up

Export Citation Format

Share Document