Genetic and nongenetic factors influencing the response to clopidogrel

Notarangelo, Maria Francesca; Bontardelli, Federico; Merlini, Piera Angelica

doi:10.2459/jcm.0b013e328364bb04

Cited by 21 publications

(18 citation statements)

References 42 publications

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“…Finally, most studies evaluated very-high risk patients, i.e., with a recent ACS or PCI, and it is unclear whether these results are applicable to lowerrisk patients, e.g., those with stable angina or history of ischemic stroke [10][11][12][26][27][28][29][30][31] . Finally, the antiplatelet activity of clopidogrel is affected by several polymorphisms (Table 2) [34] and none of these studies evaluated this parameter [10][11][12][26][27][28][29][30][31] . However, both pharmacodynamic and clinical studies suggest that there is no association between CYP2C19 genotype and the impact of PPIs on the antiplatelet effect of clopidogrel [35][36][37] .…”

Section: Introductionmentioning

confidence: 99%

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Bouziana

Τζιόμαλος

2015

WJGPT

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Clopidogrel is a widely used antiplatelet agent for the secondary prevention of cardiovascular events in patients with stable coronary heart disease, acute coronary syndromes and ischemic stroke. Even though clopidogrel is safer than aspirin in terms of risk for gastrointestinal (GI) bleeding, the elderly, and patients with a history of prior GI bleeding, with Helicobacter pylori infection or those who are also treated with aspirin, anticoagulants, corticosteroids or nonsteroidal antiinflammatory drugs are at high risk for GI complications when treated with clopidogrel. Accordingly, proton pump inhibitors are frequently administered in combination with clopidogrel to reduce the risk for GI bleeding. Nevertheless, pharmacodynamic studies suggest that omeprazole might attenuate the antiplatelet effect of clopidogrel. However, in observational studies, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination. Moreover, in the only randomized, double-blind study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/ omeprazole combination had reduced risk for GI events and similar risk for cardiovascular events than patients treated with clopidogrel and placebo. However, the premature interruption of the study and the lack of power analysis in terms of the cardiovascular endpoint do not allow definite conclusions regarding the cardiovascular safety of clopidogrel/omeprazole combination. Other proton pump inhibitors do not appear to interact with clopidogrel. Nevertheless, given the limitations of existing observational and interventional studies, the decision to administer proton pump inhibitors to patients treated with clopidogrel should be individualized based on the patient's bleeding and cardiovascular risk. Core tip: Even though pharmacodynamic studies suggest that omeprazole can attenuate the antiplatelet effect of clopidogrel, this interaction does not appear to translate into increased cardiovascular risk in patients treated with this combination in observational studies. In the only randomized, double-blind, placebo-controlled study that assessed the cardiovascular implications of combining clopidogrel and omeprazole, patients treated with clopidogrel/omeprazole combination had reduced risk for MINIREVIEWS

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Section: Introductionmentioning

confidence: 99%

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Bouziana

Τζιόμαλος

2015

WJGPT

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“…To date, research on clopidogrel resistance at the molecular level has predominantly focused on gene polymorphisms (9,31,32), rather than associations with miRNA expression in platelets. Testing VASP phosphorylation is a reliable method for the detection of clopidogrel resistance, however it lacks early detection and indicators (20).…”

Section: Discussionmentioning

confidence: 99%

Expression of miRNA-26a in platelets is associated with clopidogrel resistance following coronary stenting

Chen¹,

Qi²,

Chen³

et al. 2016

Experimental and Therapeutic Medicine

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“…Clopidogrel is more commonly used, but has several limitations including a lack of response in 4% to 30% of patients and its susceptibility to drug-drug interactions and to genetic polymorphisms. [177][178][179] Clopidogrel is a prodrug, requiring 2 metabolic steps to form the active drug. 180 The time to peak effect of clopidogrel takes as long as 24 hours.…”

Section: Summary Recommendations For Pde Inhibitorsmentioning

confidence: 99%

Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications (Second Edition)

Narouze

Benzon

Provenzano³

et al. 2017

Regional Anesthesia and Pain Medicine

118

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The American Society of Regional Anesthesia and Pain Medicine (ASRA) 2012 survey of meeting attendees showed that existing ASRA anticoagulation guidelines for regional anesthesia were insufficient for their needs. Those surveyed agreed that procedure-specific and patient-specific factors required separate guidelines for pain and spine procedures. In response, a guidelines committee was formed. After preliminary review of published complications reports and studies, the committee stratified interventional spine and pain procedures according to potential bleeding risk: low-, intermediate-, and high-risk procedures. The ASRA regional anesthesia anticoagulation guidelines were largely deemed appropriate for the low- and intermediate-risk categories, but the high-risk category required further investigation. The first guidelines specific to interventional spine and pain procedures were published in 2015. Recent reviews evaluating bleeding complications in patients undergoing specific interventional pain procedures, the development of new regional anesthesia and acute pain guidelines, and the development of new anticoagulants and antiplatelet medications necessitate complementary updated guidelines. The authors desired coordination with the authors of the recently updated regional and acute pain anticoagulation guidelines. The latest evidence was sought through extensive database search strategies and the recommendations were evidence based when available and pharmacology driven otherwise. We could not provide strength and grading of these recommendations because there are not enough well-designed large studies concerning interventional pain procedures to support such grading. Although the guidelines could not always be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide sound recommendations and the evidentiary basis for such recommendations. This publication is intended as a living document to be updated periodically with consideration of new evidence.

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Genetic and nongenetic factors influencing the response to clopidogrel

Cited by 21 publications

References 42 publications

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Clinical relevance of clopidogrel-proton pump inhibitors interaction

Expression of miRNA-26a in platelets is associated with clopidogrel resistance following coronary stenting

Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications (Second Edition)

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