Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction

Matetzky, Shlomo; Шенкман, Борис; Guetta, Victor

doi:10.1016/j.accreview.2004.08.004

Cited by 485 publications

(706 citation statements)

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“…17 For instance, the previously mentioned study by Matetzky and colleagues found an increased likelihood of recurrent cardiovascular events among patients with STsegment elevation myocardial infarction (STEMI) who were hyporesponsive to clopidogrel and underwent PCI. 18 In a different population of patients regarded as nonresponders with stable angina who underwent PCI, a higher rate of subacute stent thrombosis was identified. 19 Variability in ADP-induced aggregation is well known in patients with coronary artery disease treated with ASA therapy.…”

Section: Clopidogrelmentioning

confidence: 99%

Investigating the Mechanisms of Hyporesponse to Antiplatelet Approaches

et al. 2008

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Hyporesponsiveness, or resistance, to antiplatelet therapy may be a major contributor to poorer outcomes among cardiac patients and may be attributed to an array of mechanisms—both modifiable and unmodifiable. Recent evidence has uncovered clinical, cellular, and genetic factors associated with hyporesponsiveness. Patients with severe acute coronary syndromes (ACS), type 2 diabetes, and increased body mass index appear to be the most at risk for hyporesponsiveness. Addressing modifiable mechanisms may offset hyporesponsiveness, while recognizing unmodifiable mechanisms, such as genetic polymorphisms and diseases that affect response to antiplatelet therapy, may help identify patients who are more likely to be hyporesponsive. Hyporesponsive patients might benefit from different dosing strategies or additional antiplatelet therapies. Trials correlating platelet function test results to clinical outcomes are required. Results from these studies could cause a paradigm shift toward individualized antiplatelet therapy, improving predictability of platelet inhibition, and diminishing the likelihood for hyporesponsiveness. Copyright © 2008 Wiley Periodicals, Inc.

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Section: Clopidogrelmentioning

confidence: 99%

Investigating the Mechanisms of Hyporesponse to Antiplatelet Approaches

et al. 2008

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“…In this regard, proton pump inhibitors (PPI)s reduce the risk of bleeding in patients treated with low dose aspirin or non-steroidal antinflammatory drugs (NSAIDs), and might be an attractive way to improve the safety of dual antiplatelet therapy [2]. Biological studies have shown a broad inter-individual variability of platelet response to clopidogrel, and more recently, a low response to clopidogrel has been associated with an increased risk of ischemic events [3]. Several mechanisms have been proposed to explain this variability of response, including genetic factors and interaction with other medications.…”

Section: Introductionmentioning

confidence: 99%

The prophylactic use of a proton pump inhibitor (PPI) in patients treated with clopidogrel and aspirin for an acute coronary syndrome or placement of a coronary stent reduces the rate of upper gastrointestinal bleeding with no apparent increase in cardiovascular events

Sada¹,

Costantino

2011

Intern Emerg Med

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“…Observational studies have demonstrated that a high level of on-clopidogrel platelet aggregation (PA) can result in adverse cardiovascular events after PCI, including stent thrombosis [10][11][12][13] . In this regard, carriers of at least one reduced-function cytochrome P450 2C19 (CYP2C19) allele treated with DAPT have been reported to have low levels of the active metabolites of clopidogrel, diminished platelet inhibition and a high rate of major adverse cardiovascular events among ACS patients undergoing PCI 14) .…”

Section: Platelet Function Testsmentioning

confidence: 99%

Impact of CYP2C19 Polymorphism on Platelet Function Tests and Coagulation and Inflammatory Biomarkers in Patients Undergoing Percutaneous Coronary Intervention

Kaikita

Ono

Iwashita

et al. 2014

JAT

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Aim:Carriers of the reduced-function CYP2C19 allele receiving dual antiplatelet therapy (DAPT) with aspirin and clopidogrel exhibit diminished platelet inhibition and an increased risk of events. The purpose of this study was to investigate the effects of CYP2C19 gene variants on platelet function tests and coagulation and inflammatory biomarkers in patients undergoing elective percutaneous coronary intervention (PCI). Methods: This prospective, observational, multicenter study enrolled 104 consecutive Japanese patients undergoing elective PCI. We examined the CYP2C19 genotype, platelet function tests, the levels of coagulation and inflammatory biomarkers and the serum levels of high-sensitivity troponin T (hsTnT) before, immediately after and one, two and 28 days after PCI. Results: A total of 68 (65%) of the 104 enrolled patients were carriers of the CYP2C19 reducedfunction allele. On-clopidogrel platelet aggregation (PA), measured using light transmittance aggregometry and the VerifyNow ® P2Y12 system, and the platelet reactivity index (PRI) were significantly higher at all time points in the carriers than in the noncarriers (p＜0.05), whereas there were no differences in the levels of the coagulation and inflammatory biomarkers or serum hs-TnT. Simple and multiple logistic regression analyses identified on-clopidogrel PA and PRI as being significant predictors of carriers of the CYP2C19 reduced-function allele. Conclusions: The present study suggests that platelet function tests, but not coagulation, inflammatory or cardiac biomarkers, are useful for identifying carriers of CYP2C19 reduced-function gene variants and monitoring the efficacy of DAPT in patients undergoing elective PCI. J Atheroscler Thromb, 2014; 21:64-76.

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Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction

Cited by 485 publications

References 0 publications

Investigating the Mechanisms of Hyporesponse to Antiplatelet Approaches

Investigating the Mechanisms of Hyporesponse to Antiplatelet Approaches

The prophylactic use of a proton pump inhibitor (PPI) in patients treated with clopidogrel and aspirin for an acute coronary syndrome or placement of a coronary stent reduces the rate of upper gastrointestinal bleeding with no apparent increase in cardiovascular events

Impact of CYP2C19 Polymorphism on Platelet Function Tests and Coagulation and Inflammatory Biomarkers in Patients Undergoing Percutaneous Coronary Intervention

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