Combined influence of proton-pump inhibitors, calcium-channel blockers and CYP2C19*2 on on-treatment platelet reactivity and on the occurrence of atherothrombotic events after percutaneous coronary intervention
Harmsze, A.M.; Van Werkum, J.W.; Souverein, P.C.; Breet, N.J.; Bouman, H.J.; Hackeng, C.M.; Ruven, H.J.T.; Ten Berg, J.M.; Klungel, O.H.; De Boer, A.; Deneer, V.H.M.
(2011) Journal of Thrombosis and Haemostasis, volume 9, issue 10, pp. 1892 - 1901
(Article)
Abstract
Background: The carriage of CYP2C19*2 and the use of proton-pump inhibitors (PPIs) and calcium-channel blockers (CCBs) has been associated with the diminished efficacy of clopidogrel. However, previous studies have only assessed the isolated impact of these risk factors for clopidogrel poor response. Objectives: The aim of the present study was
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to investigate the impact of the combined presence of three risk factors for clopidogrel poor response, that is, the use of CCBs, PPIs and the carriage of CYP2C19*2, on on-treatment platelet reactivity and the occurrence of atherothrombotic events in 725 patients on dual antiplatelet therapy undergoing elective coronary stenting. Methods: In a prospective, follow-up study, on-treatment platelet reactivity was quantified using ADP-induced light transmittance aggregometry (LTA) and the VerifyNow P2Y12 assay. The clinical study endpoint was the composite of all-cause mortality, myocardial infarction, stent thrombosis and stroke at 1year after stenting. Results: Patients with either one or more than one risk factor exhibited increased platelet reactivity (mean relative increase one risk factor: 11% and >1 risk factor: 22%, respectively). Sixty-four events occurred during follow-up (8.8% of the study population). Patients with one risk factor for clopidogrel poor response did not have an increased risk of the composite endpoint. However, patients using both CCBs and PPIs and carriers of CYP2C19*2 who used CCBs had a statistically significant increased risk of the composite endpoint [hazard ratio(HR)adj2.2 95% CI, 1.0-5.3, P=0.044 and HRadj3.3 95% CI, 1.1-9.8, P=0.032, respectively]. Conclusions: The presence of more than one of the three investigated risk factors for clopidogrel poor response is associated with an increased risk of adverse cardiovascular events within 1year after elective coronary stenting. © 2011 International Society on Thrombosis and Haemostasis.
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Keywords: Clopidogrel, CYP2C19, Drug-drug interactions, Genetics, Percutaneous coronary intervention, calcium channel blocking agent, clopidogrel, cytochrome P450 2C19, proton pump inhibitor, adult, aged, anticoagulant therapy, article, cardiovascular risk, clinical trial, coronary artery disease, coronary stent, female, heart infarction, human, loading drug dose, major clinical study, male, mortality, percutaneous coronary intervention, priority journal, stent thrombosis, cerebrovascular accident, thrombocyte activation, treatment response
ISSN: 1538-7933
Publisher: Blackwell Publishing Ltd
Note: © 2011 International Society on Thrombosis and Haemostasis.
(Peer reviewed)