European Journal of Clinical Pharmacology

, Volume 62, Issue 9, pp 765–772

Case-control study on the association of upper gastrointestinal bleeding and nonsteroidal anti-inflammatory drugs in Japan

  • Choitsu Sakamoto
  • Kentaro Sugano
  • Shinichi Ota
  • Nobuhiro Sakaki
  • Shin’ichi Takahashi
  • Yukio Yoshida
  • Taku Tsukui
  • Hiroyuki Osawa
  • Yukihiro Sakurai
  • Junji Yoshino
  • Yuji Mizokami
  • Tetsuya Mine
  • Tetsuo Arakawa
  • Hajime Kuwayama
  • Katsunori Saigenji
  • Koji Yakabi
  • Tsutomu Chiba
  • Tooru Shimosegawa
  • Jane E. Sheehan
  • Susana Perez-Gutthann
  • Takuhiro Yamaguchi
  • David W. Kaufman
  • Tsugumichi Sato
  • Kiyoshi Kubota
  • Akira Terano
Pharmacoepidemiology and Prescription

DOI: 10.1007/s00228-006-0171-6

Cite this article as:
Sakamoto, C., Sugano, K., Ota, S. et al. Eur J Clin Pharmacol (2006) 62: 765. doi:10.1007/s00228-006-0171-6

Abstract

Objective

Studies in Western populations have shown the association of nonsteroidal anti-inflammatory drugs (NSAIDs) and upper gastrointestinal bleeding (UGIB). The role of Helicobacter pylori infection in NSAIDs-related UGIB remains to be studied. We conducted a case-control study in Japan to investigate these related topics.

Methods

Cases of UGIB due to duodenal or gastric ulcer, or gastritis were identified in 14 study hospitals in various areas of Japan. For each case, two controls were identified from population registries in the same district. Information on drugs and other risk factors was obtained from 175 cases and 347 controls by telephone interviews. Anti-H. pylori antibody in the urine was measured in a single laboratory for all the cases and 225 controls.

Results

The odds ratio (OR) of UGIB was 5.5 for aspirin and 6.1 for other NSAIDs (NANSAIDs) (p<0.01). The OR for regular use was higher than for occasional use both for aspirin (7.7 vs 2.0) and NANSAIDs (7.3 vs 4.1). Loxoprofen (5.9), frequently used in Japan as a safe ‘prodrug’, was significantly associated with UGIB. The odds ratio for H. pylori infection was 4.9 and the relative excess risk due to the interaction between H. pylori and the use of NSAID was 1.2 (95% CI: −5.8–8.1).

Conclusion

NSAIDs including loxoprofen increase the risk of UGIB in Japan as in Western countries, with a similar magnitude of association. There was no evidence of biological interaction between NSAIDs and H. pylori infection.

Keywords

Adverse drug effectsAnti-inflammatory agents, non-steroidalCase-control studiesGastrointestinal hemorrhageJapan

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Choitsu Sakamoto
    • 1
  • Kentaro Sugano
    • 2
  • Shinichi Ota
    • 3
  • Nobuhiro Sakaki
    • 4
  • Shin’ichi Takahashi
    • 5
  • Yukio Yoshida
    • 6
  • Taku Tsukui
    • 1
  • Hiroyuki Osawa
    • 2
  • Yukihiro Sakurai
    • 7
  • Junji Yoshino
    • 8
  • Yuji Mizokami
    • 9
  • Tetsuya Mine
    • 10
  • Tetsuo Arakawa
    • 11
  • Hajime Kuwayama
    • 12
  • Katsunori Saigenji
    • 13
  • Koji Yakabi
    • 14
  • Tsutomu Chiba
    • 15
  • Tooru Shimosegawa
    • 16
  • Jane E. Sheehan
    • 17
  • Susana Perez-Gutthann
    • 18
  • Takuhiro Yamaguchi
    • 19
  • David W. Kaufman
    • 17
  • Tsugumichi Sato
    • 20
    • 21
  • Kiyoshi Kubota
    • 20
    • 21
    • 23
  • Akira Terano
    • 22
  1. 1.Nippon Medical SchoolTokyoJapan
  2. 2.Jichi Medical SchoolTochigiJapan
  3. 3.Saitama Medical SchoolSaitamaJapan
  4. 4.Tokyo Metropolitan Bokutoh HospitalTokyoJapan
  5. 5.Kyorin University School of MedicineTokyoJapan
  6. 6.Jichi Medical School Omiya Medical CenterSaitamaJapan
  7. 7.Kanto Medical Center NTT ECTokyoJapan
  8. 8.Fujita Health University Banbuntane Hotokukai HospitalAichiJapan
  9. 9.Tokyo Medical University Kasumigaura HospitalIbarakiJapan
  10. 10.Tokai University School of MedicineKanagawaJapan
  11. 11.Osaka City University Medical SchoolOsakaJapan
  12. 12.University Hospital at KoshigayaDokkyo University School of MedicineSaitamaJapan
  13. 13.Kitasato University East HospitalKanagawaJapan
  14. 14.Teikyo University School of Medicine Ichihara HospitalChibaJapan
  15. 15.Graduate School of MedicineKyoto UniversityKyotoJapan
  16. 16.Graduate School of MedicineTohoku UniversityMiyagiJapan
  17. 17.Slone Epidemiology CenterBoston UniversityBostonUSA
  18. 18.Pfizer Worldwide DevelopmentBarcelonaSpain
  19. 19.School of Health Sciences and NursingUniversity of TokyoTokyoJapan
  20. 20.Faculty of MedicineUniversity of TokyoTokyoJapan
  21. 21.Drug Safety Research Unit JapanTokyoJapan
  22. 22.Dokkyo University School of MedicineTochigiJapan
  23. 23.Department of Pharmacoepidemiology, Faculty of MedicineUniversity of TokyoTokyoJapan