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

Alexopoulos, Dimitrios; Xanthopoulou, Ioanna; Tsigkas, Grigorios; Δαμέλου, Αναστασία; Θεοδωρόπουλος, Κωνσταντίνος; Kassimis, George; Chouchoulis, Konstantinos; Davlouros, Periklis; Chiladakis, John; Hahalis, George

doi:10.1253/circj.cj-12-0173

Cited by 10 publications

(4 citation statements)

References 40 publications

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“…The exact role played by the impaired response to P2Y12 blockade in the pathogenesis of atherothrombotic complications among CKD patients remains unclear. Recent studies demonstrated that a decreased GFR is significantly associated with a poor response to thienopyridine therapy [ 26 , 30 ]. We and others have also reported a significant interaction between CKD and high on-clopidogrel platelet reactivity (defined as a PRI VASP ≥61 %), with the latter parameter being a strong independent predictor of cardiac death [ 20 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study

et al. 2016

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BackgroundCardiovascular complications represent a major cause of morbidity and mortality for patients who received kidney transplantation (KT). However, the impact of KT and chronic immunosuppression on platelet response to clopidogrel in patients undergoing coronary or peripheral revascularization procedures remains unclear. This cohort study compares platelet responsiveness to clopidogrel as assessed byvasodilator-stimulated phosphoprotein (VASP) phosphorylation.MethodsThe study population was divided between chronic kidney disease (CKD) patients who underwent KT (n = 36) and non-transplanted CKD patients (control group, n = 126). Patients were on maintenance antiplatelet therapy with clopidogrel 75 mg daily for at least 8 days. The mean platelet reactivity index (PRI) VASP values and the prevalence of high on-treatment platelet reactivity (HPR, defined as PRI VASP ≥61 %) were compared.ResultsThe mean PRI VASP value was significantly higher in the transplant group (60.1 ± 3 vs 51.2 ± 1.6 %; p=0.014). HPR was significantly more common in the transplant group on clopidogrel maintenance therapy (58 vs. 31 %; p = 0.011). KT was the only independent predictor of HPR (odds ratio: 2.6; 95 % confidence interval: 1.03–6.27, p = 0.03). The effect of treatment with calcineurin inhibitors on clopidogrel response could not be analyzed separately from the kidney transplant status.ConclusionsKT is associated with an increased prevalence of HPR. Our results suggest that plateletfunction tests may be clinically useful for the management of this specific population.

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Section: Discussionmentioning

confidence: 99%

Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study

et al. 2016

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“…The inhibitors has been investigated and quantified for clopidogrel and prasugrel, with both agents being subject to HRPR (37)(38)(39)43).…”

Section: Phamacodynamic Studiesmentioning

confidence: 99%

Pharmacokinetics and pharmacodynamics of oral P2Y12 inhibitors during the acute phase of a myocardial infarction: A systematic review

Khan

Cox

Cotton

2016

Thrombosis Research

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Our results indicate that despite the administration of oral P2Y12 inhibitors including newer more potent agents that should allow for greater and more consistent levels of platelet inhibition, the physiological state of ST segment elevation MI (STEMI) and the co-administration of opioid based analgesia are associated with a reduction in the degree of platelet inhibition achieved following their administration.

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“…All PCR analyses were performed in 384-well plates using a Dual 384-Well GeneAmp PCR System 9700 (ABI, Foster City, CA, USA), and the end point fluorescent readings were obtained using an ABI PRISM 7900HT Sequence Detection System (ABI, Foster City, CA, USA). Duplicate samples and negative controls were betes mellitus and a decreased renal function are associated with poor responsiveness to clopidogrel [4][5][6][7][8] .…”

Section: Genotypingmentioning

confidence: 99%

Relationship Between Statin Type and Responsiveness to Clopidogrel in Patients Treated with Percutaneous Coronary Intervention: A Subgroup Analysis of the CILON-T Trial

Suh

Jin

Lee

et al. 2014

JAT

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Aim:To compare the responsiveness to clopidogrel in patients who were prescribed two different types of statins, atorvastatin vs. rosuvastatin, following percutaneous coronary intervention. Methods: A total of 915 patients were randomized according to the antiplatelet therapy strategy in the CILON-T trial. In this subgroup analysis, we included patients who took atorvastatin (20 mg/day, n = 295) or rosuvastatin (10 mg/day, n = 261) during the entire study period and underwent measurement of the P2Y12 reaction unit (PRU) values at both discharge and six months. We compared the P2Y12 reaction unit (PRU) values at six months and investigated the relationship between the genotypes of cytochrome P450 (CYP) 3A4, 3A5 and 2C19 with the PRU values at six months in both groups. Results: The baseline characteristics did not differ between the groups. There were no significant differences in the PRU values at discharge (atorvastatin 221.0±87.3 vs. rosuvastatin 217.1±84.7, p=0.59). However, the rosuvastatin group had higher PRU values than the atorvastatin group at six months (atorvastatin 226.4±79.3 vs. rosuvastatin 241.5±88.2, p = 0.033). In the genotype analysis, the number of CYP2C19 loss-of-function (LOF) alleles ( ＊ 2 or ＊ 3) was positively associated with a higher PRU value in both statin groups, and there were no significant interactions regarding the PRU values between the number of CYP 2C19 LOF alleles and the type of statin (p for interaction = 0.56). In the multivariate analysis, the use of rosuvastatin was a significant predictor of a PRU value of ＞273 (the highest tertile) (OR 1.67, 95% confidence interval 1.05-2.65, p= 0.031). Conclusions: Rosuvastatin is associated with high on-treatment platelet reactivity compared with atorvastatin following the coadministration of clopidogrel for six months. Further studies are therefore warranted to clarify the mechanism underlying this relationship.

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

Cited by 10 publications

References 40 publications

Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study

Impaired P2Y12 inhibition by clopidogrel in kidney transplant recipients: results from a cohort study

Pharmacokinetics and pharmacodynamics of oral P2Y12 inhibitors during the acute phase of a myocardial infarction: A systematic review

Relationship Between Statin Type and Responsiveness to Clopidogrel in Patients Treated with Percutaneous Coronary Intervention: A Subgroup Analysis of the CILON-T Trial

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