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.
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Acknowledgments
This investigator-initiated study was funded by an institutional research grant provided by the University of Florida College of Medicine-Jacksonville. Antonio Tello-Montoliu is a recipient of a scholarship financed by the Ministry of Education (Spain), through the National Human Resources Mobility I-D i 2008–2011 National Plan 2008–2011.
Disclosures
Dominick J. Angiolillo (corresponding author) reports receiving: honoraria for lectures from Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; Daiichi Sankyo, Inc; Astra Zeneca; Abbott Vascular; consulting fees from Bristol Myers Squibb; Sanofi-Aventis; Eli Lilly Co; Daiichi Sankyo, Inc.; The Medicines Company; Portola; Novartis; Medicure; Accumetrics; Arena Pharmaceuticals; Abbott Vascular; Astra Zeneca; Merck; Evolva; research grants from Bristol Myers Squibb; Sanofi-Aventis; GlaxoSmithKline; Otsuka; Eli Lilly Co; Daiichi Sankyo, Inc., The Medicines Company; Portola; Accumetrics; Schering-Plough; Astra-Zeneca; Eisai.
Conflict of interest
Antonio Tello-Montoliu, Murali Kodali, Salvatore D. Tomasello, Masafumi Ueno, Ronakkumar Patel, Andrew Darlington, Bhaloo Desai, Fabiana Rollini, Davide Capodanno, Theodore A. Bass: have no conflict of interest to report.
Luis A. Guzman: reports consulting fees from Astra-Zeneca and Merit Medical, José Luis Ferreiro: reports honoraria for lectures from Eli Lilly Co and Daiichi Sankyo, Inc.
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Tello-Montoliu, A., Ferreiro, J.L., Kodali, M.K. et al. Impact of renal function on clopidogrel-induced antiplatelet effects in coronary artery disease patients without diabetes mellitus. J Thromb Thrombolysis 36, 14–17 (2013). https://doi.org/10.1007/s11239-012-0828-1
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DOI: https://doi.org/10.1007/s11239-012-0828-1