Genetic and Nongenetic Factors Affecting Clopidogrel Response in the Egyptian Population

Khalil, Basma M.; Shahin, Mohamed H.; Solayman, Mohamed Hassan M.; Langaee, Taimour; Schaalan, Mona F.; Gong, Yan; Hammad, Lamiaa N.; Al-Mesallamy, H O; Hamdy, Nadia M.; El-Hammady, Walid; Johnson, Julie A.

doi:10.1111/cts.12383

Cited by 40 publications

(37 citation statements)

References 45 publications

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“…A systematic review and meta-analysis by Bauer et al (2011) revealed no substantial or consistent influence of CYP2C19 variants on the clinical efficacy of clopidogrel and risk of MACE. In contrast, the groups of Mega and Han reported significantly increased risk of MACE in association with CYP2C19 * 2 and * 3 variants (Mega et al, 2010b; Han et al, 2015; Khalil et al, 2016). …”

Section: Introductionmentioning

confidence: 92%

Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention

Sun

Chen

et al. 2016

Front. Pharmacol.

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The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for 1 year for evidence of MACE. CYP2C19 *2 and *3 variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM, CYP2C19*1/*2, or *1/*3), poor metabolizer (PM, CYP2C19*2/*2, *2/*3, or *3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM, CYP2C19*1/*1). In total, 519 patients completed 1 year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR = 2.664 (1.397–5.193), P = 0.004). The data suggest that CYP2C19*2 and *3 variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly, CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE.

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Section: Introductionmentioning

confidence: 92%

Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention

Sun

Chen

et al. 2016

Front. Pharmacol.

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“…In recent years, the focus of pharmacogenomics research has evolved from the traditional emphasis on discovering genetic determinants of drug exposure (pharmacokinetics), to a broader definition that includes genes and pathways that underlie the pharmacologic and toxic response to therapeutics (pharmacodynamics). In this issue, Khalil et al . and Hamadeh et al .…”

Section: Example Topics Of Interest For Clinical and Translational Scmentioning

confidence: 95%

Transforming Translation: Impact of Clinical and Translational Science

Kroetz

2016

Clinical Translational Sci

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“…Age and BMI were significantly associated with clopidogrel response [75,76]. Older age was independently associated with a higher rate of high residual on-treatment platelet reactivity with both clopidogrel and ticagrelor in 494 patients on dual antiplatelet therapy [77].…”

Section: Non-genetic Factors Influencing Clopidogrel Responsementioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives

Zhang

Tang

et al. 2017

IJERPH

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Clopidogrel has significantly reduced the incidence of recurrent atherothrombotic events in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous coronary intervention (PCI). However, recurrence events still remain, which may be partly due to inadequate platelet inhibition by standard clopidogrel therapy. Genetic polymorphisms involved in clopidogrel’s absorption, metabolism, and the P2Y12 receptor may interfere with its antiplatelet activity. Recent evidence indicated that epigenetic modification may also affect clopidogrel response. In addition, non-genetic factors such as demographics, disease complications, and drug-drug interactions can impair the antiplatelet effect of clopidogrel. The identification of factors contributing to the variation in clopidogrel response is needed to improve platelet inhibition and to reduce risk for cardiovascular events. This review encompasses the most recent updates on factors influencing pharmacokinetic and pharmacodynamic responses to clopidogrel.

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Genetic and Nongenetic Factors Affecting Clopidogrel Response in the Egyptian Population

Cited by 40 publications

References 45 publications

Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention

Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention

Transforming Translation: Impact of Clinical and Translational Science

Pharmacokinetic and Pharmacodynamic Responses to Clopidogrel: Evidences and Perspectives

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