Clinical, clinicopathologic, and gastrointestinal changes from administration of clopidogrel, prednisone, or combination in healthy dogs: A double-blind randomized trial.
Animals
Clopidogrel
/ administration & dosage
Dogs
Double-Blind Method
Drug Therapy, Combination
Gastrointestinal Hemorrhage
/ chemically induced
Glucocorticoids
/ administration & dosage
Platelet Aggregation Inhibitors
/ administration & dosage
Prednisone
/ administration & dosage
Stomach Ulcer
/ chemically induced
antiplatelet
corticosteroid
gastrointestinal bleeding
glucocorticoid
thromboprophylaxis
ulcer
Journal
Journal of veterinary internal medicine
ISSN: 1939-1676
Titre abrégé: J Vet Intern Med
Pays: United States
ID NLM: 8708660
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
19
06
2019
accepted:
23
09
2019
pubmed:
9
10
2019
medline:
27
3
2020
entrez:
9
10
2019
Statut:
ppublish
Résumé
Dogs with immune-mediated disease often receive glucocorticoids with clopidogrel, but ulcerogenic effects of current protocols are unknown. To compare gastrointestinal endoscopic findings among dogs administered clopidogrel, prednisone, and combination treatment. Twenty-four healthy research dogs. 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. 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. 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.
Sections du résumé
BACKGROUND
BACKGROUND
Dogs with immune-mediated disease often receive glucocorticoids with clopidogrel, but ulcerogenic effects of current protocols are unknown.
HYPOTHESIS/OBJECTIVES
OBJECTIVE
To compare gastrointestinal endoscopic findings among dogs administered clopidogrel, prednisone, and combination treatment.
ANIMALS
METHODS
Twenty-four healthy research dogs.
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31593364
doi: 10.1111/jvim.15630
pmc: PMC6872608
doi:
Substances chimiques
Glucocorticoids
0
Platelet Aggregation Inhibitors
0
Clopidogrel
A74586SNO7
Prednisone
VB0R961HZT
Types de publication
Journal Article
Randomized Controlled Trial, Veterinary
Langues
eng
Sous-ensembles de citation
IM
Pagination
2618-2627Informations de copyright
© 2019 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
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