Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis.
OBJECTIVE
To assess whether corticosteroids are associated with increased risk of gastrointestinal bleeding or perforation.


METHODS
Systematic 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.


METHODS
Literature search using MEDLINE, EMBASE and Cochrane Database of Systematic Reviews between 1983 and 22 May 2013.


METHODS
Outcome 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.


RESULTS
159 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).


CONCLUSIONS
Corticosteroid 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.
Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
Sigrid
S
Narum
Department of Pharmacology, Regional Medicines Information & Pharmacovigilance Centre (RELIS), Oslo University Hospital, Oslo, Norway.
Tone
T
Westergren
Norwegian Knowledge Centre for the Health Services, Oslo, Norway Department of Pharmacology, University of Oslo, Oslo, Norway.
Marianne
M
Klemp
D000305:Adrenal Cortex Hormones / Q000009:adverse effects*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced* / Q000453:epidemiology*; D006801:Humans; D007416:Intestinal Perforation / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013275:Stomach Rupture / Q000139:chemically induced
D000305:Adrenal Cortex Hormones
Clinical Pharmacology; Epidemiology