Spironolactone and colitis: increased mortality in rodents and in humans.
Spironolactone and colitis: increased mortality in rodents and in humans.
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DOI：
10.1002/ibd.21929
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发表时间：
2012-07
影响因子：
4.9
通讯作者：
Higgins, Peter D. R.
中科院分区：
文献类型：
--
作者：
Johnson, Laura A.;Govani, Shail M.;Joyce, Joel C.;Waljee, Akbar K.;Gillespie, Brenda W.;Higgins, Peter D. R.
Crohn’s disease causes intestinal inflammation leading to intestinal fibrosis. Spironolactone is an anti-fibrotic medication commonly used in heart failure to reduce mortality. We examined whether spironolactone is anti-fibrotic in the context of intestinal inflammation. In vitro, spironolactone repressed fibrogenesis in TGFβ-stimulated human colonic myofibroblasts. However, spironolactone therapy significantly increased mortality in two rodent models of inflammation-induced intestinal fibrosis, suggesting spironolactone could be harmful during intestinal inflammation. Since IBD patients rarely receive spironolactone therapy, we examined whether spironolactone use was associated with mortality in a common cause of inflammatory colitis, Clostridium difficile infection (CDI). Spironolactone use during CDI infection was associated with increased mortality in a retrospective cohort of 4008 inpatients (15.9% vs. 9.1%, n=390 deaths, p<0.0001). In patients without liver disease, the adjusted OR for inpatient mortality associated with 80 mg spironolactone was 1.99 (95% CI: 1.51 – 2.63) In contrast to the main effect of spironolactone mortality, multivariable modeling revealed a protective interaction between liver disease and spironolactone dose. The adjusted odds ratio for mortality after CDI was 1.96 (95% CI: 1.50 – 2.55) for patients without liver disease on spironolactone vs. 1.28 (95% CI: 0.82 – 2.00) for patients with liver disease on spironolactone, when compared to a reference group without liver disease or spironolactone use. We propose that discontinuation of spironolactone in patients without liver disease during CDI could reduce hospital mortality by 2-fold, potentially reducing mortality from CDI by 35,000 patients annually across Europe and the US.
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影响因子：
3
作者：
Gullulu, Mustafa;Akdag, Ibrahim;Savci, Vahide
通讯作者：
Savci, Vahide
影响因子：
6.7
作者：
OVERDIEK, HWPM;HERMENS, WAJJ;MERKUS, FWHM
通讯作者：
MERKUS, FWHM
影响因子：
5.9
作者：
Rajagopalan, S;Pitt, B
通讯作者：
Pitt, B
影响因子：
7.2
作者：
DEYO, RA;CHERKIN, DC;CIOL, MA
通讯作者：
CIOL, MA
影响因子：
64.8
作者：
Lyras, Dena;O'Connor, Jennifer R.;Howarth, Pauline M.;Sambol, Susan P.;Carter, Glen P.;Phumoonna, Tongted;Poon, Rachael;Adams, Vicki;Vedantam, Gayatri;Johnson, Stuart;Gerding, Dale N.;Rood, Julian I.
通讯作者：
Rood, Julian I.