title: The effect of acenocoumarol on the antiplatelet effect of clopidogrel.
abstract: Patients exhibiting high on-clopidogrel platelet reactivity (HPR) are at an increased risk of atherothrombotic events following percutaneous coronary interventions (PCI). The use of concomitant medication which is metabolised by the hepatic cytochrome P450 system, such as phenprocoumon, is associated with HPR. We assessed the level of platelet reactivity on clopidogrel in patients who received concomitant treatment with acenocoumarol (another coumarin derivative). Patients scheduled for PCI were included in a prospective, single centre, observational registry. Patients who were adequately pre-treated with clopidogrel were eligible for this analysis, which included 1,582 patients, of whom 104 patients (6.6%) received concomitant acenocoumarol treatment. Platelet reactivity, as measured with the VerifyNow P2Y12 assay and expressed in P2Y12 Reaction Units (PRU), was significantly higher in patients on concomitant acenocoumarol treatment (mean PRU 229 ± 88 vs 187 ± 95; p < 0.001). In patients with concomitant acenocoumarol use, the proportion of patients with HPR was higher, defined as PRU > 208 (57.7% vs 41.1%; p=0.001) and PRU ≥ 236 (49.0% vs 31.4%; p< 0.001). In multivariable analysis, concomitant acenocoumarol use was independently associated with a higher PRU and the occurrence of HPR defined as PRU ≥ 236 (OR 2.00, [1.07-3.79]), but not with HPR defined as PRU > 208 (OR 1.37, [0.74-2.54]). PRU also was significantly increased after 1:1 propensity matching (+28.2; p < 0.001). As this was an observational study, confounding by indication cannot be excluded, although multivariable analyses and propensity matching were performed. The impact of the findings from this hypothesis-generating study on clinical outcome requires further investigation.
authors.forename: Willem J M
authors.initials: WJ
authors.lastname: Dewilde
authors.affiliation: Dr. Paul W. A. Janssen, Cardiology, St. Antonius Hospital, Koekoekslaan 1, Nieuwegein Utrecht 3430, The Netherlands, Tel.: +31 088 3209679, Fax: +31 084 0033422, E-mail: p.janssen@antoniusziekenhuis.nl.
authors.forename: Paul W A
authors.initials: PW
authors.lastname: Janssen
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Bergmeijer
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Kelder
authors.forename: Christian M
authors.initials: CM
authors.lastname: Hackeng
authors.forename: Jurriën M
authors.initials: JM
authors.lastname: ten Berg
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage* / Q000009:adverse effects; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D004347:Drug Interactions; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009426:Netherlands; D016017:Odds Ratio; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D019338:Polypharmacy; D057216:Propensity Score; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D012042:Registries; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000925:Anticoagulants; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D000077144:Clopidogrel; D000074:Acenocoumarol; D013988:Ticlopidine
keywords: Platelet aggregation; VerifyNow; acenocoumarol; clopidogrel; high on-treatment platelet reactivity; oral anticoagulation