Effect of Cytochrome P450 Polymorphisms on Platelet Reactivity After Treatment With Clopidogrel in Acute Coronary Syndrome

Frère, Corinne; Cuisset, Thomas; Morange, Pierre‐Emmanuel; Quilici, Jacques; Camoin-Jau, Laurence; Saut, Noémie; Faille, Dorothée; Lambert, Marc; Juhan‐Vague, I.; Bonnet, Jean‐Louis; Alessi, Marie‐Christine

doi:10.1016/j.amjcard.2007.11.065

Cited by 184 publications

(111 citation statements)

References 29 publications

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“…[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Based on our results and findings from the several studies, it is conceivable that genotyping will be beneficial to the patients who are on clopidogrel treatment. [36][37][38] The cost-effectiveness analysis based on the TRITON-TIMI 38 trial have suggested that genotyping patients before selecting antiplatelet treatment could offer more value in the clinical setting than putting on drug therapy without regard to pharmacogenomic test results.…”

Section: Discussionsupporting

confidence: 53%

“…30,31 Patients with laboratorydefined resistance have shown increased risk of atherothrombosis. 32,33 In the present study, we observed that in homozygous variant (PM) group, 4 out of 6 patients developed acute stent thrombosis within one week of PCI. In a study by Zhu et al, in Chinese patients showed that the CYP2C19 LOF alleles (*2 and *3) are risk factors for the prognosis of patients who have undergone carotid artery stenting and are on clopidogrel therapy.…”

Section: Discussionmentioning

confidence: 46%

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Association of Polymorphisms in CYP2C19 with the Efficacy of Clopidogrel Therapy in South Indian Patients Undergoing Percutaneous Coronary Intervention

Kumari¹,

Ravella²,

Kumar³

et al. 2017

JCDR

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Background:The dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been considered as the standard of care in the setting of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI). Recent evidence supports a role of loss-of-function (LOF) variants in the CYP2C19 as a determinant of clopidogrel response. Carriers of the CYP2C19*2 LOF allele has found to have the reduced pharmacodynamic response to clopidogrel and worse clinical outcome as compared with non-carriers in Asian countries including Indian population. However, it is unknown whether the time course of the antiplatelet effects of clopidogrel differs according to CYP2C19 genotype in South Indian patients with ACS. Methods: We assessed the platelet reactivity in the early and late phases of ACS according to CYP2C19 genotypes. Eighty six consecutive in-patients who were admitted with ACS at our center were enrolled in the study. The determination of platelet aggregation was done by using a platelet aggregometer and genetic analysis was done by PCR-RFLP method. Results: The numbers of patients carrying the CYP2C19*1/*1 (extensive metabolizer, EM), *1/*2 (Intermediate metabolizer, IM), *2/*2 (poor metabolizer PM), genotypes were 22 (30.9%), 37 (52.1%), 12 (16.9%), respectively. Time course of platelet aggregation from baseline to the late phase among the 3 genotypes indicate that there was statistically significant at 30 th day of treatment (p=0.004) between wild versus hetero and homozygous variant alleles. The percentage of patients shifted to prasugrel from clopidogrel due to non-response were 4 (8%), 11(29%), 6 (50%) in wild, heterozygous and homozygous variant alleles. In homozygous group, we found 4 out of 6 patients developed acute stent thrombosis within one week of PCI. Conclusion: We observed that the CYP2C19*2 and CYP2C19*1/*2 are the major determinants of clopidogrel efficacy. Acute stent thrombosis was observed in patients carrying CYP2C19*2 variant allele

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 46%

Association of Polymorphisms in CYP2C19 with the Efficacy of Clopidogrel Therapy in South Indian Patients Undergoing Percutaneous Coronary Intervention

Kumari¹,

Ravella²,

Kumar³

et al. 2017

JCDR

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“…11 The two-step activation process involving a series of cytochrome P-450 (CYP) isoenzymes, is susceptible to the interference of genetic polymorphisms and drug-drug interactions. 12,13 Proton pump inhibitors that inhibit CYP2C19, particularly omeprazole, decrease clopidogrel-induced platelet inhibition ex vivo, but there is currently no conclusive clinical evidence that co-administration of clopidogrel and proton pump inhibitors increases the risk of ischaemic events in addition, clopidogrel (and prasugrel) absorption is regulated by P-glycoprotein (encoded by ABCB1), which is an ATP-dependent efflux pump that transports various molecules across extracellular and intracellular membranes. It is expressed, among other places, on intestinal epithelial cells, where increased expression or function can affect the bioavailability of drugs that are substrates.…”

Section: Clopidogrelmentioning

confidence: 99%

Platelet adenosine diphosphate receptor antagonists: ticlopidine to ticagrelor—a long continuing journey

Kaul

Mansoor

2012

Indian Heart Journal

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Platelet aggregation plays a central role in the pathogenesis of atherothrombosis. Platelet adenosine diphosphate (ADP) receptor antagonists (ticlopidine, clopidogrel, prasugrel, and ticagrelor) are a major advance in the treatment of atherothrombotic diseases, especially acute coronary syndromes (ACS). Ticlopidine was the first thienopyridine introduced into clinical practice, but its potentially serious haematological side-effects limited its use and it was quickly eclipsed by clopidogrel. Clinical trials established aspirin plus clopidogrel as the standard dual anti-platelet therapy in patients with ACS and patients undergoing percutaneous coronary intervention (PCI) with stenting. Clopidogrel was found to have pharmacokinetic and pharmacodynamic limitations. Prasugrel is the next approved thienopyridine that has shown superior efficacy in ACS patients undergoing PCI in comparison to clopidogrel, although at the cost of a higher bleeding risk. Ticagrelor is the latest non-thienopyridine ADP receptor blocker that is potent, effective, reversible, and relatively safer as compared to clopidogrel.Both prasugrel and ticagrelor are more potent than clopidogrel. The data so far suggests that ticagrelor has a wider applicability in usage in patients with ACS as compared to prasugrel. Prasugrel however seems to be better tolerated. Search is on for newer more potent but safer anti-platelet agents.

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“…The mechanisms underlying the variability of response to clopidogrel may be related to poor patient compliance, differences in clopidogrel dosing, gastric absorption problems, and varying availability and clearance of the active metabolite (O'queli et al, 2007). Genetic factors including polymorphisms of hepatic CYP3A-have received special attention (Frere et al, 2008). There have been reports of concerns that proton pump inhibitors (PPIs) may interfere with clopidogrel's ability to inhibit platelet aggregation, thereby increasing the risk of rehospitalization or death in association with ACS (Li et al, 2004;Juurlink et al, 2009;Ho et al, 2009).…”

Section: Clopidogrelmentioning

confidence: 99%

Evaluation of Anti-Ischemic Therapy in Coronary Artery Disease: A Review

Al-Nimer¹

2012

Coronary Artery Diseases

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Effect of Cytochrome P450 Polymorphisms on Platelet Reactivity After Treatment With Clopidogrel in Acute Coronary Syndrome

Cited by 184 publications

References 29 publications

Association of Polymorphisms in CYP2C19 with the Efficacy of Clopidogrel Therapy in South Indian Patients Undergoing Percutaneous Coronary Intervention

Association of Polymorphisms in CYP2C19 with the Efficacy of Clopidogrel Therapy in South Indian Patients Undergoing Percutaneous Coronary Intervention

Platelet adenosine diphosphate receptor antagonists: ticlopidine to ticagrelor—a long continuing journey

Evaluation of Anti-Ischemic Therapy in Coronary Artery Disease: A Review

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