Key result
Compared to clopidogrel alone, healthy dogs receiving prednisone with clopidogrel were 11 times more likely to have an excessive antiplatelet response (P=0.03).
Why the study?
Glucocorticoids cause hypercoagulability, but whether they counteract the antiplatelet effects of clopidogrel was unknown.
Does clopidogrel and prednisone alter platelet function in healthy dogs?
RCT (n=24)
Double-blinded
randomized
Does clopidogrel and prednisone alter platelet function in healthy dogs?
Odds Ratio: 11
p-value: p=0.03
Co-administration of clopidogrel and prednisone increases platelet dysfunction in healthy dogs compared to clopidogrel alone.
May increase bleeding risk with co-administration in dogs; leaves open relevance to clinical patients or outcomes.
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.
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Thomason et al. (2020) conducted an RCT in healthy dogs (n=24). prednisone with clopidogrel vs. clopidogrel alone, prednisone alone, or placebo was evaluated on excessive response in platelet function (OR 11, p=0.03). Compared to clopidogrel alone, healthy dogs receiving prednisone with clopidogrel were 11 times more likely to have an excessive antiplatelet response (P=0.03).
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