Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis

Abstract

ObjectiveTo assess whether corticosteroids are associated with increased risk of gastrointestinal bleeding or perforation.DesignSystematic review and meta-analysis of randomised, double-blind, controlled trials comparing a corticosteroid to placebo for any medical condition or in healthy participants. Studies with steroids given either locally, as a single dose, or in crossover studies were excluded.Data sourcesLiterature search using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews between 1983 and 22 May 2013.Outcome measureOutcome measures were the occurrence of gastrointestinal bleeding or perforation. Predefined subgroup analyses were carried out for disease severity, use of non-steroidal anti-inflammatory drugs (NSAIDs) or gastroprotective drugs, and history of peptic ulcer.Results159 studies (N=33 253) were included. In total, 804 (2.4%) patients had a gastrointestinal bleeding or perforation (2.9% and 2.0% for corticosteroids and placebo). Corticosteroids increased the risk of gastrointestinal bleeding or perforation by 40% (OR 1.43, 95% CI 1.22 to 1.66). The risk was increased for hospitalised patients (OR 1.42, 95% CI 1.22 to 1.66). For patients in ambulatory care, the increased risk was not statistically significant (OR 1.63, 95% CI 0.42 to 6.34). Only 11 gastrointestinal bleeds or perforations occurred among 8651 patients in ambulatory care (0.13%). Increased risk was still present in subgroup analyses (studies with NSAID use excluded; OR 1.44, 95% CI 1.20 to 1.71, peptic ulcer as an exclusion criterion excluded; OR 1.47, 95% CI 1.21 to 1.78, and use of gastroprotective drugs excluded; OR 1.42, 95% CI 1.21 to 1.67).ConclusionsCorticosteroid use was associated with increased risk of gastrointestinal bleeding and perforation. The increased risk was statistically significant for hospitalised patients only. For patients in ambulatory care, the total occurrence of bleeding or perforation was very low, and the increased risk was not statistically significant.

Associations between drugs and small‐bowel mucosal bleeding: Multicenter capsule‐endoscopy study

“…30 In upper gastrointestinal bleeding, a Japanese guideline and another meta-analysis reported that the risk of peptic ulcer complications increases when NSAIDs are given with steroids or anticoagulants. 2,31 We confirmed this effect in relation to small-bowel overt bleeding. NSAIDs induce small-bowel injuries, and other antithrombotic drugs, such as thienopyridine, or steroids, might exacerbate the injury or impair tissue repair and potentially induce small-bowel overt bleeding.…”

“…1,2 Several studies have reported that NSAIDs cause mucosal breaks and increase the mean number of mucosal injuries in healthy subjects. [3][4][5] In hospital-based studies, use of NSAIDs was associated with an increased risk of small-bowel mucosal injury, including ulceration, compared with non-use.…”

Use of proton-pump inhibitors among adults: a Danish nationwide drug utilization study

“…To do this, we calculated the annual proportion of PPI users that had filled one or more prescriptions for the following drugs known to be ulcerogenic or to increase the risk of bleeding peptic ulcer [Bhatt et al 2008;Dall et al 2009;Gómez-Outes et al 2013;Narum et al 2014 [Thygesen et al 2011].…”

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions

“…GI hemorrhage is a rare side effect of etanercept treatment (37) and was not found in our retrospective supportive care group (data not shown). However, systemic corticosteroids have been known to be associated with an increased risk of GI hemorrhage (37,44).…”