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Glucocorticoids and the Risk of Peptic Ulcer Bleeding: Case–Control Analysis Based on Swiss Claims Data



Controversy exists as to whether glucocorticoids (GC) are ulcerogenic per se and may thus cause peptic ulcer bleeding (PUB) independent of concomitantly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs).


To investigate the association between GC use and PUB with or without co-medication with NSAIDs.


We conducted a case–control study using administrative claims data from the Swiss health insurance company Helsana. We identified 1191 cases with incident PUB between 2012 and 2016 and matched up to 10 PUB-free controls to each case on age, sex, region and number of years insured with Helsana. We compared prior GC exposure between cases and controls using multivariate conditional logistic regression analyses controlling for several potential confounders. Patients with or without concomitant NSAID exposure were analysed separately.


Patients with prior exposure to both GC and NSAIDs were five times more likely to experience PUB than patients who neither used GC nor NSAIDs (adjusted odds ratio [adj. OR] 4.80, 95% CI 3.55–6.71). Although the risk of PUB among patients who used NSAIDs without GC was increased threefold (adj. OR 3.20, 95% CI 2.59–3.95), we observed only a moderately increased risk among patients who used GC alone without NSAIDs (adj. OR 1.63, 95% CI 1.20–2.42).


The use of NSAIDs with or without GC was associated with a markedly higher risk of PUB compared with GC monotherapy. Use of GC alone was associated with a moderately increased risk of PUB, which might be causal or attributed to confounding by indication.

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  1. Lanas A, Chan FK. Peptic ulcer disease. Lancet. 2017;390(10094):613–24.

    Article  PubMed  Google Scholar 

  2. Guslandi M. Steroid ulcers: any news? World J Gastrointest Pharmacol Ther. 2013;4(3):39–40.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Narum S, Westergren T, Klemp M. Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ Open. 2014;4(5):e004587.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tseng CL, Chen YT, Huang CJ, Luo JC, Peng YL, Huang DF, et al. Short-term use of glucocorticoids and risk of peptic ulcer bleeding: a nationwide population-based case-crossover study. Aliment Pharmacol Ther. 2015;42(5):599–606.

    Article  PubMed  CAS  Google Scholar 

  5. Garcia Rodriguez LA, Lin KJ, Hernandez-Diaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123(10):1108–15.

    Article  PubMed  CAS  Google Scholar 

  6. Nielsen GL, Sorensen HT, Mellemkjoer L, Blot WJ, McLaughlin JK, Tage-Jensen U, et al. Risk of hospitalization resulting from upper gastrointestinal bleeding among patients taking corticosteroids: a register-based cohort study. Am J Med. 2001;111(7):541–5.

    Article  PubMed  CAS  Google Scholar 

  7. Hernandez-Diaz S, Rodriguez LA. Steroids and risk of upper gastrointestinal complications. Am J Epidemiol. 2001;153(11):1089–93.

    Article  PubMed  CAS  Google Scholar 

  8. Piper JM, Ray WA, Daugherty JR, Griffin MR. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991;114(9):735–40.

    Article  PubMed  CAS  Google Scholar 

  9. de Abajo FJ, Gil MJ, Bryant V, Timoner J, Oliva B, Garcia-Rodriguez LA. Upper gastrointestinal bleeding associated with NSAIDs, other drugs and interactions: a nested case–control study in a new general practice database. Eur J Clin Pharmacol. 2013;69(3):691–701.

    Article  PubMed  CAS  Google Scholar 

  10. WHO Collaborating Centre for Drug Statistics Methodology. Guidelines for ATC classification and DDD assignment 2017. Oslo 2016. Accessed 12 Jul 2017.

  11. World Health Organization. International Statistical Classification of Diseases and Related Health Problems, 10th Revision. 2016. Accessed 12 Jul 2017.

  12. Luo JC, Shin VY, Liu ES, So WH, Ye YN, Chang FY, et al. Non-ulcerogenic dose of dexamethasone delays gastric ulcer healing in rats. J Pharmacol Exp Ther. 2003;307(2):692–8.

    Article  PubMed  CAS  Google Scholar 

  13. Luo JC, Shin VY, Liu ES, Ye YN, Wu WK, So WH, et al. Dexamethasone delays ulcer healing by inhibition of angiogenesis in rat stomachs. Eur J Pharmacol. 2004;485(1–3):275–81.

    Article  PubMed  CAS  Google Scholar 

  14. Carson JL, Strom BL, Schinnar R, Duff A, Sim E. The low risk of upper gastrointestinal bleeding in patients dispensed corticosteroids. Am J Med. 1991;91(3):223–8.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Christoph R. Meier.

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The study was funded by Helsana Group, Zurich, Switzerland.

Conflict of interest

Daphne Reinau, Matthias Schwenkglenks, Mathias Früh, Andri Signorell, Eva Blozik and Christoph R. Meier have no conflicts of interest directly relevant to the content of this study.

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Reinau, D., Schwenkglenks, M., Früh, M. et al. Glucocorticoids and the Risk of Peptic Ulcer Bleeding: Case–Control Analysis Based on Swiss Claims Data. Drug Saf 41, 725–730 (2018).

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