Case-control study on the association of upper gastrointestinal bleeding and nonsteroidal anti-inflammatory drugs in Japan
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.
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.
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).
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.
KeywordsAdverse drug effects Anti-inflammatory agents, non-steroidal Case-control studies Gastrointestinal hemorrhage Japan
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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