title: Impact of renal function on clopidogrel-induced antiplatelet effects in coronary artery disease patients without diabetes mellitus.
abstract: Diabetes mellitus (DM) is the most important predictor of chronic kidney disease (CKD), and pharmacodynamic (PD) studies have shown that DM patients with impaired renal function are characterized by reduced clopidogrel response. However, post-hoc PD studies conducted in unselected cohorts, composed of both DM and non-DM patients, have reached controversial findings on the effects of CKD on clopidogrel response, likely attributed to patient heterogeneity. The impact of renal function on clopidogrel response in non-DM patients remains unexplored and represented the aim of this prospective investigation. We conducted a prospective PD investigation in non-DM patients with and without CKD defined as an estimated glomerular filtration rate (eGFR) below or above 60 mL/min, respectively. All patients had known coronary artery disease and were on maintenance aspirin therapy. PD assessments were assessed at baseline and 2 and 24 h after a 600 mg loading dose of clopidogrel. PD assays included light transmission aggregometry (LTA) using 5 and 20 μmol ADP with and without PGE1 and flow cytometric assessment of the phosphorylation status of the vasodilator-stimulated phosphoprotein (VASP) to determine the platelet reactivity index. A total of 60 patients were studied (n = 30 eGFR ≥60 mL/min; n = 30 eGFR <60 mL/min). At baseline there were no differences between groups. Following clopidogrel loading dose administration, levels of on-treatment platelet reactivity were similar between groups at 2 and 24 h as measured with LTA and VASP. Accordingly, there were no differences in rates of high on-treatment platelet reactivity between groups. In non-DM patients with CAD, the presence of impaired renal function is not associated with differences in clopidogrel-induced antiplatelet effects compared with patients with preserved renal function.
authors.affiliation: University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL 32209, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Ferreiro
authors.forename: Murali K
authors.initials: MK
authors.lastname: Kodali
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Salvatore D
authors.initials: SD
authors.lastname: Tomasello
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.forename: Davide
authors.initials: D
authors.lastname: Capodanno
authors.forename: Andrew
authors.initials: A
authors.lastname: Darlington
authors.forename: Ronakkumar
authors.initials: R
authors.lastname: Patel
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000503:physiopathology; D003920:Diabetes Mellitus; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine