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Non-steroidal anti-inflammatory drugs and risk of lower gastrointestinal adverse events: a nationwide study in Taiwan
  1. Chia-Hsuin Chang1,2,
  2. Jou-Wei Lin3,
  3. Hsi-Chieh Chen1,
  4. Chuei-Wen Kuo4,
  5. Wen-Yi Shau5,
  6. Mei-Shu Lai1
  1. 1Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
  2. 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
  3. 3Cardiovascular Center, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Yun-Lin, Taiwan
  4. 4National Health Insurance Mediation Committee, Department of Health, Executive Yuan, Taipei, Taiwan
  5. 5Division of Health Technology Assessment, Center for Drug Evaluation, Taipei, Taiwan
  1. Correspondence to Professor Mei-Shu Lai, Institute of Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; mslai{at}


Objective Only limited studies have evaluated the risk of non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) and coxibs for lower gastrointestinal (GI) adverse outcomes. The objective of this study was to evaluate risks of lower GI adverse events associated with use of celecoxib, oral and parenteral nsNSAIDs.

Design Retrospective case–crossover study.

Setting Records of all patients aged ≥20 years hospitalised for lower GI adverse events (bleeding from small or large intestine, perforation, and complicated diverticular disease) in 2006 were retrieved using ICD-9-CM diagnosis codes from inpatient claims from the Taiwan National Health Insurance database.

Interventions Case periods were defined for each patient as 1–30 days prior to hospital admission date and control period as 91–120 days prior to hospital admission date. The pharmacy prescription database was searched for NSAID use during case and control periods.

Main outcome measures We calculated adjusted self-matched ORs and 95% CIs with a conditional logistic regression model to determine the associations between NSAID use and lower GI adverse outcomes.

Results A total of 1297 patients hospitalised for lower GI adverse events were included. Celecoxib was associated with an adjusted OR of 2.33 (95% CI 0.97 to 5.59); the association became statistically significant (OR: 3.26, 95% CI 1.07 to 9.91) when a different control period (31–60 days) was applied. Both oral and parenteral nsNSAIDs significantly increased risk for lower GI adverse events (OR: 2.26, 95% CI 1.78 to 2.85 and OR: 5.64, 95% CI 3.24 to 9.82, respectively).

Conclusions Oral and parenteral NSAIDs were associated with significantly increased risk for lower GI adverse events. Celecoxib also increased risk to a comparable extent, despite risk estimates being affected slightly by the control period chosen for comparison. The association of NSAIDs with specific lower GI adverse events and long-term complications requires further investigation.

  • Gastrointestinal haemorrhage
  • anti-inflammatory agents, Non-steroidal
  • crossover studies
  • gastrointestinal haemorrhage

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  • Chia-Hsuin Chang and Jou-Wei Lin contributed equally to this work.

  • Funding This study was supported by Taiwan Department of Health grant DOH098-TD-D-113-098016. H-C Chen had full access to all study data and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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