Clinical, clinicopathologic, and gastrointestinal changes from administration of clopidogrel, prednisone, or combination in healthy dogs: A double-blind randomized trial.

Abstract

BACKGROUND: Dogs with immune-mediated disease often receive glucocorticoids with clopidogrel, but ulcerogenic effects of current protocols are unknown. HYPOTHESIS/OBJECTIVES: To compare gastrointestinal endoscopic findings among dogs administered clopidogrel, prednisone, and combination treatment. ANIMALS: Twenty-four healthy research dogs. METHODS: Double-blinded, placebo-controlled randomized trial. Dogs received placebo, clopidogrel (2-3 mg/kg q24h), prednisone (2 mg/kg q24h), or prednisone with clopidogrel PO for 28&#x2009;days. Attitude, food intake, vomiting, and fecal score were determined daily. Clinicopathologic testing was performed at baseline and on day 28. Gastrointestinal hemorrhages, erosions, and ulcers were numerated by 2 blinded investigators for endoscopies performed on days 0, 14, and 28, and endoscopic mucosal lesion scores were calculated. Results were compared using mixed model, split-plot repeated measures ANOVAs and generalized estimating equation proportional odds models as appropriate. P&#x2009;<&#x2009;.05 was considered significant. RESULTS: Clinical signs of gastrointestinal bleeding were not noted. Endoscopic mucosal lesion scores differed significantly by group (F[3, 20] = 12.8, P&#x2009;<&#x2009;.001) and time (F[2, 40] = 8.3, P&#x2009;<&#x2009;.001). Posthoc analysis revealed higher lesion scores in the prednisone-receiving groups (P&#x2009;&#x2264;&#x2009;.006 for each) and on day 14 (P&#x2009;&#x2264;&#x2009;.007 for each). Ulcers were identified in 4 dogs administered prednisone and 3 dogs administered prednisone/clopidogrel. Odds of having endoscopic mucosal lesion scores &#x2265;4 were 7-times higher for dogs in prednisone (95%CI 1.1, 43.0; P = .037) and prednisone-clopidogrel (95%CI 1.1, 43.4; P = .037) groups than those in the placebo group. CONCLUSIONS AND CLINICAL IMPORTANCE: Gastrointestinal bleeding and ulceration occur commonly in healthy dogs administered prednisone or prednisone/clopidogrel treatment, but not clopidogrel monotherapy. Though lesions are severe in many cases, they are not accompanied by clinical signs.