Association of Estimated GFR With Platelet Inhibition in Patients Treated With Clopidogrel

作者：Muller Clotilde; Caillard Sophie; Jesel Laurence; El Ghannudi Soraya; Ohlmann Patrick; Sauleau Erik; Hannedouche Thierry; Gachet Christian; Moulin Bruno; Morel Olivier^*

来源：American Journal of Kidney Diseases, 2012, 59(6): 777-785.

DOI：10.1053/j.ajkd.2011.12.027

• Thrombosis
• platelet
• renal insufficiency
• clopidogrel
• resistance

Background: The reasons that decreased glomerular filtration rate (GFR) might alter the clinical efficacy of clopidogrel are poorly understood. %26lt;br%26gt;Study Design: In this study, we sought to evaluate whether decreased GFR alters platelet response to clopidogrel in patients receiving a maintenance dose of clopidogrel (75 mg/d for at least 8 days). %26lt;br%26gt;Settings %26 Participants: 126 consecutive patients categorized by estimated GFR: stages 1-2 (%26gt;60 mL/min/1.73 m(2); n = 29), stage 3a (45-59 mL/min/1.73 m(2); n = 21); stage 3b (30-44 mL/min/1.73 m(2); n = 26), stage 4 (15-29 mL/min/1.73 m(2); n = 14), and stage 5 (%26lt;15 mL/min/1.73 m(2); n = 36) were prospectively enrolled. %26lt;br%26gt;Predictor: Residual platelet reactivity, defined in the VASP (Vasodilator Stimulated Phosphoprotein) flow cytometry test as platelet reactivity index (PRI) %26gt;= 61% and in the VerifyNow turbidimetric-based assay as a value %26gt;235 PRU (adenosine diphosphate receptor reaction units) or percentage of platelet inhibition %26lt;15%. %26lt;br%26gt;Outcomes: We examined factors associated with low response to clopidogrel using logistic regression. %26lt;br%26gt;Results: A significant relationship between estimated GFR, PRI, PRU, and percentage of inhibition was found. The prevalence of residual platelet reactivity was highest in patients with GFR stage 5. PRI %26gt;= 61% occurred in 52.8% of patients with stage 5 versus 30.8% of stage 3b and 24.1% of stages 1-2 (P = 0.1). PRU %26gt;235 was found in 63.6% of patients with stage 5 versus 36.8% of stage 3b and 17.2% of stages 1-2 (P = 0.005). Inhibition %26lt;15% affected 66.7% of patients with stage 5 versus 21.1% of stage 3b and 17.2% of stages 1-2 (P %26lt; 0.001). In the multivariable model, GFR stage 5 (adjusted prevalence ratio [PR], 3.10; 95% CI, 1.23-9.43; P = 0.02), and obesity (adjusted PR, 1.92; 95% CI, 1.34-2.23; P = 0.004) were the sole predictors of residual platelet reactivity. %26lt;br%26gt;Limitations: Interference of hemodialysis with the pharmacokinetics of clopidogrel could not be excluded. %26lt;br%26gt;Conclusion: GFR stage 5 is associated with substantial impairment of platelet inhibition independently of diabetes mellitus. Am J Kidney Dis. 59(6):777-785.

• 出版日期2012-6