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 mg/kg/d), prednisone (2 mg/kg/d), or prednisone with clopidogrel PO for 28 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 < .05 was considered significant.

Results: Closure times differed by treatment (F [3, 20] = 10.5; P < .001), time (F [2, 40] = 14.3; P < .001), and treatment-by-time (F [6, 40] = 3.4; P = .01). Area under the curve (AUC) differed by treatment (F [3, 20] = 19.6; P < .001), time (F [2, 40] = 35.4; P < .001), and treatment-by-time (F [6, 40] = 13.5; P < .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 = .03) more likely to have an excessive response.

Conclusions and clinical importance: Administration of clopidogrel/prednisone increases platelet dysfunction in healthy dogs.

Keywords: antiplatelet; corticosteroid; glucocorticoid; immune-mediated hemolytic anemia; thromboprophylaxis.