Residual Platelet Reactivity After Clopidogrel Loading in Patients With ST-Elevation Myocardial Infarction Undergoing an Unexpectedly Delayed Primary Percutaneous Coronary Intervention  - Impact on Intracoronary Thrombus Burden and Myocardial Perfusion -

Vavuranakis, Manolis; Vrachatis, Dimitrios; Papaioannou, Theodore G.; Archontakis, Stefanos; Kalogeras, Konstantinos; Kariori, Maria; Gafou, Anthi; Moldovan, Carmen; Tzamalis, Panagiotis; Stefanadis, Christodoulos

doi:10.1253/circj.cj-11-0077

Cited by 17 publications

(8 citation statements)

References 24 publications

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“…Visible procedural-related adverse events, such as side-branch occlusion, dissection, disruption of collateral flow, and distal embolization, have been identified as extrinsic factors leading to PMI. 2-4 Recently, accumulative evidences showed that intrinsic platelet activation played a pivotal role in the pathophysiological development of PMI 5, 6 and that pretreatment with clopidogrel has significantly decreased the risk of PMI. 6 Accordingly, current common clinical practice is pretreatment with a 300-mg loading dose of clopidogrel at least 6 h before the procedure in patients undergoing elective intervention.…”

Section: Discussionmentioning

confidence: 99%

“…4 It has been demonstrated that platelet activation and aggregation play pivotal roles in the pathophysiological development of ischemic events during PCI and that pretreatment with clopidogrel has significantly reduced PMI. 5, 6 Of note, variability in response to the fixed dose of clopidogrel is well established. 7, 8 The CYP2C19 loss-of-function (LOF) allele has been identified as a genetic determinant of variant response to clopidogrel.…”

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confidence: 99%

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Association of CYP2C19 Genotype With Periprocedural Myocardial Infarction After Uneventful Stent Implantation in Chinese Patients Receiving Clopidogrel Pretreatment

Qian

Sun

et al. 2012

Circ J

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Background: High platelet reactivity (HPR) after clopidogrel treatment is linked to an increased risk of periprocedural myocardial infarction (PMI). The occurrence of PMI that could be associated with CYP2C19 genotype status was our hypothesis. Methods and Results:A total of 233 patients with non-ST elevation acute coronary syndromes (NSTACS) undergoing uneventful elective percutaneous coronary intervention were included. Platelet reactivity was assessed by Thrombelastograph at 24 h after 300 mg clopidogrel loading. HPR was defined as ≥70% adenosine diphosphateinduced platelet aggregation. The CYP2C19*2 and *3 loss-of-function (LOF) alleles were determined using DNA microarray method. Patients with PMI had significantly higher on-clopidogrel platelet reactivity compared to those without PMI (60.0±24.4% vs. 43.0±24.0%, P<0.001). HPR was more frequently observed in patients with PMI and was the strongest risk factor of PMI in multivariate analysis (ORadj=4.348, 95% CI: 1.846-10.241, P=0.001). Furthermore, the incidence of HPR was significantly associated with the carriage of 2 CYP2C19 LOF alleles. Compared with non-carriers, patients carrying 2 CYP2C19 LOF alleles had a 3.000-fold increased risk (95% CI: 1.071-8.400, P=0.037) for PMI in multivariate analysis. However, inclusion of HPR as a covariate in the regression model changed the significant relationship between the carriage of 2 CYP2C19 LOF alleles and PMI.Conclusions: Among Chinese patients with NSTACS, carriers with 2 CYP2C19 LOF alleles are more prone to HPR, which is associated with an increased risk for PMI. (Circ J 2012; 76: 2773 - 2778

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Association of CYP2C19 Genotype With Periprocedural Myocardial Infarction After Uneventful Stent Implantation in Chinese Patients Receiving Clopidogrel Pretreatment

Qian

Sun

et al. 2012

Circ J

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“…7,8, 10 In patients with STEMI undergoing unexpectedly delayed catheterization, a lower degree of platelet inhibition after clopidogrel LD was associated with larger intracoronary thrombus and worse post-PCI myocardial flow and perfusion. 20 The clinical sequelae of upstream or peri-interventional clopidogrel use are controversial. Data from registries and a metaanalysis showed that pretreatment with clopidogrel was associated with higher initial patency and improved outcome, including the combined endpoint of death and myocardial infarction at 1 year.…”

Section: Discussionmentioning

confidence: 99%

Predictors of High On-Treatment Platelet Reactivity Early After Clopidogrel Loading in ST-Elevation Myocardial Infarction

Alexopoulos¹,

Xanthopoulou²,

Tsigkas³

et al. 2012

Circ J

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“…In some reports, HTPR in response to clopidogrel therapy affected up to 40% of treated individuals [ 9 , 94 , 95 ]. Of importance, the HTPR independently associated with larger intracoronary thrombus burden, worse post-PCI myocardial flow and perfusion, higher ischemic risk, and frequency of adverse cardiovascular outcomes such as stent thrombosis, myocardial infarction, stroke, and death in several studies on platelet aggregation, and therefore carries a poor prognosis in patients with ACS treated with clopidogrel after PCI [ 25 , 96 , 97 , 98 , 99 , 100 ]. HTPR can be partially overcome by assuring loading of clopidogrel prior to PCI, with administration of the higher dose (600 mg, compared to 300 mg) [ 101 , 102 ].…”

Section: Pharmacogenomics Eramentioning

confidence: 99%

Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine

Brown

Pereira

2018

JPM

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Variability in response to antiplatelet therapy can be explained in part by pharmacogenomics, particularly of the CYP450 enzyme encoded by CYP2C19. Loss-of-function and gain-of-function variants help explain these interindividual differences. Individuals may carry multiple variants, with linkage disequilibrium noted among some alleles. In the current pharmacogenomics era, genomic variation in CYP2C19 has led to the definition of pharmacokinetic phenotypes for response to antiplatelet therapy, in particular, clopidogrel. Individuals may be classified as poor, intermediate, extensive, or ultrarapid metabolizers, based on whether they carry wild type or polymorphic CYP2C19 alleles. Variant alleles differentially impact platelet reactivity, concentration of plasma clopidogrel metabolites, and clinical outcomes. Interestingly, response to clopidogrel appears to be modulated by additional factors, such as sociodemographic characteristics, risk factors for ischemic heart disease, and drug-drug interactions. Furthermore, systems medicine studies suggest that a broader approach may be required to adequately assess, predict, preempt, and manage variation in antiplatelet response. Transcriptomics, epigenomics, exposomics, miRNAomics, proteomics, metabolomics, microbiomics, and mathematical, computational, and molecular modeling should be integrated with pharmacogenomics for enhanced prediction and individualized care. In this review of pharmacogenomic variation of CYP450, a systems medicine approach is described for tailoring antiplatelet therapy in clinical practice of precision cardiovascular medicine.

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Residual Platelet Reactivity After Clopidogrel Loading in Patients With ST-Elevation Myocardial Infarction Undergoing an Unexpectedly Delayed Primary Percutaneous Coronary Intervention - Impact on Intracoronary Thrombus Burden and Myocardial Perfusion -

Cited by 17 publications

References 24 publications

Association of CYP2C19 Genotype With Periprocedural Myocardial Infarction After Uneventful Stent Implantation in Chinese Patients Receiving Clopidogrel Pretreatment

Association of CYP2C19 Genotype With Periprocedural Myocardial Infarction After Uneventful Stent Implantation in Chinese Patients Receiving Clopidogrel Pretreatment

Predictors of High On-Treatment Platelet Reactivity Early After Clopidogrel Loading in ST-Elevation Myocardial Infarction

Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine

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