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

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 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 < .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 < .001) and time (F[2, 40] = 8.3, P < .001). Posthoc analysis revealed higher lesion scores in the prednisone‐receiving groups (P ≤ .006 for each) and on day 14 (P ≤ .007 for each). Ulcers were identified in 4 dogs administered prednisone and 3 dogs administered prednisone/clopidogrel. Odds of having endoscopic mucosal lesion scores ≥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.