Clinical, clinicopathologic, and gastrointestinal changes from aspirin, prednisone, or combination treatment in healthy research dogs: A double-blind randomized trial.
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:
Sep 2019
Sep 2019
Historique:
received:
20
12
2018
accepted:
11
07
2019
pubmed:
10
8
2019
medline:
25
1
2020
entrez:
10
8
2019
Statut:
ppublish
Résumé
Dogs with immune-mediated disease are often coadministered glucocorticoids and aspirin, but ulcerogenic effects of current protocols are unknown. To compare gastrointestinal changes among dogs administered aspirin, prednisone, and combination treatment. Twenty-four healthy research dogs. Double-blinded, placebo-controlled randomized trial of dogs administered placebo, aspirin (2 mg/kg q24h), prednisone (2 mg/kg q24h), or combination treatment PO for 28 days. Clinical signs were recorded daily, with laboratory work performed at baseline and day 28. Gastrointestinal mucosal hemorrhages, erosions, and ulcers were numerated for endoscopic studies performed on days 0, 14, and 28; endoscopic mucosal lesion scores were calculated. Results were compared using mixed model repeated-measures analyses of variance and generalized estimating equation proportional odds models. P < .05 was considered significant. Gastric mucosal lesion scores differed by treatment-by-time (F[6, 40] = 4.4, P = .002), treatment (F[3, 20] = 7.1, P = .002), and time (F[2, 40] = 18.9, P < .001). Post hoc analysis revealed increased scores in the aspirin (day 14 only), prednisone, and prednisone/aspirin groups during treatment. Ulcers were identified on 14 studies, representing 10 dogs. Dogs receiving prednisone and prednisone/aspirin had 11.1 times (95% CI, 1.7-73.6) and 31.5 times (95% CI, 3.5-288.0) higher odds, respectively, of having endoscopic mucosal lesion scores ≥4 than dogs receiving placebo (P ≤ .01). Gastrointestinal bleeding occurs commonly in dogs administered aspirin, prednisone, or prednisone/aspirin treatment, with higher lesion scores for dogs receiving combination treatment. Even severe lesions are not accompanied by clinical signs.
Sections du résumé
BACKGROUND
BACKGROUND
Dogs with immune-mediated disease are often coadministered glucocorticoids and aspirin, but ulcerogenic effects of current protocols are unknown.
OBJECTIVES
OBJECTIVE
To compare gastrointestinal changes among dogs administered aspirin, prednisone, and combination treatment.
ANIMALS
METHODS
Twenty-four healthy research dogs.
METHODS
METHODS
Double-blinded, placebo-controlled randomized trial of dogs administered placebo, aspirin (2 mg/kg q24h), prednisone (2 mg/kg q24h), or combination treatment PO for 28 days. Clinical signs were recorded daily, with laboratory work performed at baseline and day 28. Gastrointestinal mucosal hemorrhages, erosions, and ulcers were numerated for endoscopic studies performed on days 0, 14, and 28; endoscopic mucosal lesion scores were calculated. Results were compared using mixed model repeated-measures analyses of variance and generalized estimating equation proportional odds models. P < .05 was considered significant.
RESULTS
RESULTS
Gastric mucosal lesion scores differed by treatment-by-time (F[6, 40] = 4.4, P = .002), treatment (F[3, 20] = 7.1, P = .002), and time (F[2, 40] = 18.9, P < .001). Post hoc analysis revealed increased scores in the aspirin (day 14 only), prednisone, and prednisone/aspirin groups during treatment. Ulcers were identified on 14 studies, representing 10 dogs. Dogs receiving prednisone and prednisone/aspirin had 11.1 times (95% CI, 1.7-73.6) and 31.5 times (95% CI, 3.5-288.0) higher odds, respectively, of having endoscopic mucosal lesion scores ≥4 than dogs receiving placebo (P ≤ .01).
CONCLUSIONS AND CLINICAL IMPORTANCE
CONCLUSIONS
Gastrointestinal bleeding occurs commonly in dogs administered aspirin, prednisone, or prednisone/aspirin treatment, with higher lesion scores for dogs receiving combination treatment. Even severe lesions are not accompanied by clinical signs.
Identifiants
pubmed: 31397009
doi: 10.1111/jvim.15577
pmc: PMC6766539
doi:
Substances chimiques
Aspirin
R16CO5Y76E
Prednisone
VB0R961HZT
Types de publication
Journal Article
Randomized Controlled Trial, Veterinary
Langues
eng
Sous-ensembles de citation
IM
Pagination
1977-1987Subventions
Organisme : University of Tennessee, Knoxville, Acree Research Chair of Medicine endowment.
Informations 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.
Références
Gastroenterol Jpn. 1975;10(4):271-82
pubmed: 1234104
J Vet Pharmacol Ther. 2018 Feb;41(1):60-67
pubmed: 28664658
Pharmacoepidemiol Drug Saf. 2016 Nov;25(11):1245-1252
pubmed: 27594378
Vet Clin Pathol. 1998;27(4):107-111
pubmed: 12075537
Dev Biol. 1982 Feb;89(2):294-8
pubmed: 7056437
Am J Gastroenterol. 2007 Mar;102(3):507-15
pubmed: 17338735
Am J Vet Res. 1999 Aug;60(8):977-81
pubmed: 10451208
Acta Hepatogastroenterol (Stuttg). 1977 Feb;24(1):11-4
pubmed: 848241
Biochem Pharmacol. 1998 Oct 1;56(7):905-13
pubmed: 9774152
J Vet Intern Med. 2013 Jan-Feb;27(1):141-9
pubmed: 23278865
J Vet Med Sci. 2012 Sep;74(9):1103-8
pubmed: 22531101
J Vet Emerg Crit Care (San Antonio). 2019 Mar;29(2):121-131
pubmed: 30729652
Biochem Pharmacol. 1997 Jul 15;54(2):241-8
pubmed: 9271328
J Vet Emerg Crit Care (San Antonio). 2019 Jan;29(1):37-48
pubmed: 30654424
J Pharmacol Exp Ther. 1993 Sep;266(3):1306-11
pubmed: 8371138
Can J Vet Res. 1994 Apr;58(2):134-7
pubmed: 8004538
Bone Joint Res. 2014 May;3(5):146-9
pubmed: 24837005
Free Radic Biol Med. 1997;23(1):8-18
pubmed: 9165292
Phys Chem Chem Phys. 2010 Feb 28;12(8):2011-7
pubmed: 20145871
Am J Vet Res. 1983 Jul;44(7):1233-7
pubmed: 6603803
Inflammopharmacology. 2009 Feb;17(1):15-22
pubmed: 19139829
Pharmacol Ther. 2014 Jan;141(1):69-78
pubmed: 23993980
J Vet Intern Med. 1999 Sep-Oct;13(5):472-7
pubmed: 10499732
J Biol Chem. 1986 Dec 25;261(36):16883-8
pubmed: 3782147
Mol Cell Biochem. 1999 Dec;202(1-2):31-6
pubmed: 10705992
J Vet Intern Med. 2019 Sep;33(5):1977-1987
pubmed: 31397009
J Vet Intern Med. 2009 May-Jun;23(3):482-7
pubmed: 19422469
J Vet Intern Med. 2000 Jan-Feb;14(1):33-6
pubmed: 10668814
J Vet Intern Med. 2003 May-Jun;17(3):282-90
pubmed: 12774967
N Z Vet J. 1996 Oct;44(5):179-81
pubmed: 16031928
J Formos Med Assoc. 2012 Dec;111(12):705-10
pubmed: 23265750
Vet J. 2015 Mar;203(3):290-5
pubmed: 25665921
J Vet Intern Med. 2007 May-Jun;21(3):367-77
pubmed: 17552439
Am J Vet Res. 1999 Aug;60(8):982-5
pubmed: 10451209
Surg J (N Y). 2017 Dec 29;3(4):e191-e196
pubmed: 29302621
J Vet Intern Med. 2018 Nov;32(6):1823-1840
pubmed: 30378711
J Biol Chem. 1979 Oct 10;254(19):9379-84
pubmed: 226517
Clin Gastroenterol Hepatol. 2017 Dec;15(12):1882-1889.e1
pubmed: 28634133
Br J Clin Pharmacol. 2001 Nov;52(5):563-71
pubmed: 11736865
J Clin Invest. 1970 Dec;49(12):2198-204
pubmed: 5480846
J Physiol Pharmacol. 2009 Dec;60 Suppl 7:79-86
pubmed: 20388949
Br Med J. 1980 Feb 23;280(6213):527-8
pubmed: 6966172
J Vet Intern Med. 2019 May;33(3):1141-1172
pubmed: 30847984
Am J Vet Res. 2004 Jun;65(6):810-8
pubmed: 15198222
Aliment Pharmacol Ther. 2006 Jan 15;23(2):235-42
pubmed: 16393302
Biochem J. 1995 Jan 1;305 ( Pt 1):59-64
pubmed: 7826354
J Am Vet Med Assoc. 2005 Jun 1;226(11):1869-80
pubmed: 15934255
Biochim Biophys Acta. 1984 Aug 21;800(3):233-41
pubmed: 6087914
J Vet Med Sci. 2007 Apr;69(4):353-63
pubmed: 17485922
Am J Vet Res. 1997 Nov;58(11):1320-3
pubmed: 9361899
J Vet Intern Med. 2006 May-Jun;20(3):682-6
pubmed: 16734108
Mol Cell Biochem. 1993 Aug 25;125(2):115-25
pubmed: 8283967
Biochem J. 1992 Jun 1;284 ( Pt 2):305-12
pubmed: 1318028