Effects of clopidogrel and prednisone on platelet function in healthy dogs.

Abstract

BACKGROUND: Glucocorticoids cause hypercoagulability, but it is unknown if they counteract clopidogrel's antiplatelet effects. HYPOTHESIS/OBJECTIVES: Determine the effects of clopidogrel and prednisone on platelet function. ANIMALS: Twenty-four healthy dogs. METHODS: Double-blinded, placebo-controlled randomized trial. Platelet function was evaluated using a platelet function analyzer and impedance aggregometry (days 0, 14, and 28) for dogs treated with placebo, clopidogrel (2-3&#x2009;mg/kg/d), prednisone (2&#x2009;mg/kg/d), or prednisone with clopidogrel PO for 28&#x2009;days. Results were categorized as nonresponder versus responder (platelet function analyzer), and inadequate, ideal, or excessive response (aggregometry). Results were compared using mixed model, split-plot repeated measures analysis of variance and generalized estimating equation proportional odds models. P <&#x2009;.05 was considered significant. RESULTS: Closure times differed by treatment (F [3, 20] = 10.5; P&#x2009;< .001), time (F [2, 40] = 14.3; P <&#x2009;.001), and treatment-by-time (F [6, 40] = 3.4; P&#x2009;= .01). Area under the curve (AUC) differed by treatment (F [3, 20] = 19.6; P&#x2009;< .001), time (F [2, 40] = 35.4; P <&#x2009;.001), and treatment-by-time (F [6, 40] = 13.5; P&#x2009;< .001). Based on closure times, 5/6 dogs each in the clopidogrel and prednisone/clopidogrel groups were responders. All dogs in the prednisone/clopidogrel group were overcontrolled based on AUC (days 14 and 28), whereas 5/6 (day 14) and 2/6 (day 28) dogs treated with clopidogrel were overcontrolled. Compared to clopidogrel, dogs receiving prednisone/clopidogrel were 11 times (P =&#x2009;.03) more likely to have an excessive response. CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of clopidogrel/prednisone increases platelet dysfunction in healthy dogs.