title: Effect of proton-pump inhibitors on the risk of lower gastrointestinal bleeding associated with NSAIDs, aspirin, clopidogrel, and warfarin.
abstract: BACKGROUND
  We investigated the effects of proton-pump inhibitors (PPIs) on lower gastrointestinal bleeding (LGIB) and of their interactions with nonsteroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin, clopidogrel, and warfarin on LGIB risk.
  
  
  METHODS
  We prospectively studied 355 patients emergently hospitalized for LGIB and 8,221 nonbleeding patients. All patients underwent colonoscopy. Smoking, alcohol drinking, drug exposure, and the Charlson comorbidity index score were assessed before colonoscopy. Adjusted odds ratios (AOR) of LGIB were estimated.
  
  
  RESULTS
  LGIB was significantly associated with older age, higher comorbidity index, and NSAID, aspirin, clopidogrel, or warfarin use. PPI use was significantly associated with older age, male sex, being a current alcohol drinker, higher comorbidity index, and NSAID, aspirin, clopidogrel, warfarin, acetaminophen, or corticosteroid use. Multivariate analysis adjusted by the confounding factors revealed LGIB was not significantly associated with PPI use (AOR 0.87; 95 % confidence interval 0.68-1.13; p = 0.311), or specifically with omeprazole (AOR 1.18; p = 0.408), esomeprazole (AOR 0.76; p = 0.432), lansoprazole (AOR 0.93; p = 0.669), or rabeprazole (AOR 0.63; p = 0.140). In the interaction model, no significant interactions were observed between PPIs and NSAIDs (AOR 1.40; p = 0.293), aspirin (AOR 1.09; p = 0.767), clopidogrel (AOR 0.99, p = 0.985), or warfarin (AOR 1.52; p = 0.398).
  
  
  CONCLUSIONS
  This large case-control study demonstrated that PPI use did not lead to an increased risk of LGIB, regardless of the type of PPI used. Further, LGIB risk was not affected by PPI use, irrespective of concomitant therapy with NSAIDs, low-dose aspirin, clopidogrel, or warfarin.
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan. nnagata_ncgm@yahoo.co.jp.
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Nagata
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Niikura
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Aoki
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Sakurai
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Moriyasu
authors.affiliation: Department of Clinical Research and Informatics, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Shimbo
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Sekine
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Okubo
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Yokoi
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Yanase
authors.affiliation: Department of Gastroenterology and Hepatology, International Clinical Research Center, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Akiyama
authors.affiliation: Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Uemura
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000925:Anticoagulants / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects; D016022:Case-Control Studies; D000077144:Clopidogrel; D004347:Drug Interactions; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D011446:Prospective Studies; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives; D014859:Warfarin / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors; D054328:Proton Pump Inhibitors; D014859:Warfarin; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Antisecretory drugs; Drug–drug interaction; Lower gastrointestinal tract hemorrhage