Impact of Cytochrome P450 2C19 Loss-of-Function Polymorphism and of Major Demographic Characteristics on Residual Platelet Function After Loading and Maintenance Treatment With Clopidogrel in Patients Undergoing Elective Coronary Stent Placement

Hochholzer, Willibald; Trenk, Dietmar; Fromm, Martin F.; Valina, Christian; Stratz, Christian; Bestehorn, Hans-Peter; Büttner, Heinz Joachim; Neumann, Franz‐Josef

doi:10.1016/j.jacc.2010.02.031

Cited by 290 publications

(224 citation statements)

References 35 publications

(49 reference statements)

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“…In clopidogrel users, diabetes and hypercholesterolaemia were associated with a higher risk of antiplatelet drug nonpersistence. Although this was unexpected, it might be partly explained by the concern of a pharmacokinetic interaction between atorvastatin and clopidogrel in patients with hypercholesterolaemia 26, and diabetes was reported as a predictor of insufficient antiplatelet response to clopidogrel 27. Patients with previous CAD, who also have a higher risk for recurrent cardiovascular events, had a lower risk of clopidogrel nonpersistence but a higher risk of DAPT nonpersistence.…”

Section: Discussionmentioning

confidence: 95%

Patterns of antiplatelet drug use after a first myocardial infarction during a 10‐year period

Yasmina

Boer

Deneer

et al. 2016

Brit J Clinical Pharma

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AimsThe aims of the present study were to assess antiplatelet drug use patterns after a first myocardial infarction (MI) and to evaluate the determinants of antiplatelet nonpersistence.MethodsThe present study was conducted in 4690 patients from the Utrecht Cardiovascular Pharmacogenetics cohort with a first MI between 1986 and 2010, who were followed for a maximum of 10 years. Medication use and event diagnosis were obtained from the Dutch PHARMO Record Linkage System. Antiplatelet drug users were classified as persistent users (gap between prescriptions ≤90 days), nonpersistent users (>90‐day gap and no refills), and restarters (a new prescription after a >90‐day gap). The association between potential determinants and antiplatelet nonpersistence was analysed using Cox regression.ResultsThe proportions of persistent users decreased from 84.0% at the 1‐year follow‐up to 32.8% at 10 years for any antiplatelet drug, and 77.3% to 27.5% for aspirin; and 39.0% to 6.4% for clopidogrel at 6 years. Most nonpersistent users restarted antiplatelet drugs later, leading to 89.3% overall antiplatelet drug users at 10 years after MI. Diabetes (hazard ratio [HR] 0.44; 0.32–0.60), hypertension (HR 0.77; 0.60–0.99), hypercholesterolaemia (HR 0.49; 0.39–0.62) and more recent MI diagnosis period (2003–2007: HR 0.69, 0.61–0.79; 2008–2010: HR 0.38, 0.19–0.77, compared to ≤ 2002 period) lowered the risk of antiplatelet nonpersistence, while vitamin K antagonist (VKA) comedication (HR 18.97; 16.91–21.28) increased this risk.ConclusionsA large proportion of patients with a first MI still used antiplatelet drugs after 10 years. The frequent discontinuations during this time frame are expected to reduce the effectiveness of antiplatelet drugs as secondary prevention of cardiovascular diseases. Diabetes, hypertension, hypercholesterolaemia, VKA comedication and MI diagnosis period were determinants of antiplatelet nonpersistence.

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Section: Discussionmentioning

confidence: 95%

Patterns of antiplatelet drug use after a first myocardial infarction during a 10‐year period

Yasmina

Boer

Deneer

et al. 2016

Brit J Clinical Pharma

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“…The presence of a gene polymorphism resulting in loss of function of the drug-metabolizing enzyme CYP2C19 was found to be an important factor. 23,24 A recent study from the Thrombolysis in Myocardial Infarction (TIMI) study group confirmed that heterozygote and homozygote carriers of the allele retain high platelet function on clopidogrel treatment. 25 This study demonstrated that increasing daily doses of clopidogrel can produce levels similar to those in noncarriers in heterozygotes.…”

Section: Discussionmentioning

confidence: 98%

Clopidogrel Resistance Is Associated with Thromboembolic Complications in Patients Undergoing Neurovascular Stenting

Fifi¹,

Brockington²,

Narang

et al. 2012

AJNR Am J Neuroradiol

136

101

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“…In a combined model, age, body mass index and presence or absence of diabetes accounted for 1% each of platelet aggregation variability. CYP2C19*2 carrier status alone accounted for 5.2% of platelet aggregation variability and CYP2C19*2 plus clinical variables was accounted for 11.5% of platelet aggregation [36]. In the POPULAR study, CYP2C19*2 genotype was associated with approximately 4-6% and clinical variables with 9-17% variability in on-treatment platelet reactivity as assessed by ADP-induced platelet aggregation and VerifyNow P2Y12 assay.…”

Section: Influence Of Cyp2c19 Polymorphisms On Clopidogrel Metabolismmentioning

confidence: 93%

Pharmacogenomics of Oral P2Y12 Receptor Blockers

Apte¹

2013

J Pharmacogenomics Pharmacoproteomics

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Impact of Cytochrome P450 2C19 Loss-of-Function Polymorphism and of Major Demographic Characteristics on Residual Platelet Function After Loading and Maintenance Treatment With Clopidogrel in Patients Undergoing Elective Coronary Stent Placement

Abstract: Thus, our study does not suggest that, in patients critically dependent on adequate platelet inhibition, genotyping alone or in combination with clinical factors can replace phenotyping of platelet function. (Effect of Clopidogrel Loading and Risk of PCI [EXCELSIOR]; NCT00457236).

Cited by 290 publications

References 35 publications

Patterns of antiplatelet drug use after a first myocardial infarction during a 10‐year period

Patterns of antiplatelet drug use after a first myocardial infarction during a 10‐year period

Clopidogrel Resistance Is Associated with Thromboembolic Complications in Patients Undergoing Neurovascular Stenting

Pharmacogenomics of Oral P2Y12 Receptor Blockers

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