European Journal of Clinical Pharmacology

, Volume 62, Issue 9, pp 765–772 | Cite as

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

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 effects Anti-inflammatory agents, non-steroidal Case-control studies Gastrointestinal hemorrhage Japan 

Notes

Acknowledgements

This study was financially supported by Pfizer and Astellas Pharma Inc. We thank all the persons who participated in the study, all gastroenterologists who ascertained case patients in the participated hospitals, and Emi Sakata for her assistance. We also thank the following investigators who contributed to the acquisition of data: Yasuhiro Yamamoto, Futoshi Ogawa (Nippon Medical School); Kiichi Satoh, Hiroshi Kawata (Jichi Medical School); Yukinori Imai (Saitama Medical School); Takao Wakabayashi (Fujita Health University Banbuntane Hotokukai Hospital); Shuuhei Miura (Tokyo Medical University Kasumigaura Hospital); Akemi Ito, Kenichi Watanabe (Tokai University School of Medicine); Kazuhide Higuchi (Osaka City University Medical School, Osaka, Japan); Morio Takahashi (University Hospital at Koshigaya, Dokkyo University School of Medicine); Satoshi Tanabe (Kitasato University East Hospital); Hiroshi Seno, Hiroshi Nakase (Graduate School of Medicine, Kyoto University); Shuichi Ohara, Hitoshi Sekine, Akira Imatani, Tomoyuki Koike, Katsunori Iijima (Graduate School of Medicine, Tohoku University); Hideyuki Hiraishi, Tetsuya Nakamura, Takako Sasai, Yoichiro Fujii (Dokkyo University School of Medicine).

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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

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