title: Effect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants.
abstract: OBJECTIVE
  After the withdrawal of some cyclooxygenase-2 (COX-2) selective inhibitors, traditional nonsteroidal anti-inflammatory drug (NSAID) use has increased, but without additional prevention strategies against upper gastrointestinal (GI) complications in many cases. Here, we report the effect of antisecretory drugs and nitrates on the risk of upper GI peptic ulcer bleeding (UGIB) associated with nonselective NSAIDs, aspirin, antiplatelet agents, and anticoagulants.
  
  
  METHODS
  This case-control study matched 2,777 consecutive patients with UGIB (confirmed by endoscopy) with 5,532 controls (2:1). Adjusted relative risks (RR) of UGIB are reported.
  
  
  RESULTS
  Proton pump inhibitors (PPIs) (RR 0.33, 95% confidence interval [CI] 0.27-0.39), H2-receptor antagonists (H2-RAs) (RR 0.65, 95% CI 0.50-0.85), and nitrates (RR 0.52, 95% CI 0.38-0.70) reduced UGIB risk. PPI use was associated with greater reductions among both traditional NSAID (RR 0.13, 95% CI 0.09-0.19 vs RR 0.30, 95% CI 0.17-0.53 with H2-RAs; RR 0.48, 95% CI 0.19-1.24 with nitrates) and low-dose aspirin users (RR 0.32, 95% CI 0.22-0.51 vs RR 0.40, 95% CI 0.19-0.73 with H2-RA; RR 0.69, 95% CI 0.36-1.04 with nitrates), and among patients taking clopidogrel (RR 0.19, 95% CI 0.07-0.49). For patients taking anticoagulants, use of nitrates, H2-RA, or PPIs was not associated with a significant effect on UGIB risk.
  
  
  CONCLUSIONS
  Antisecretory agent or nitrate treatment is associated with reduced UGIB RR in patients taking NSAID or aspirin. Only PPI therapy was associated with a marked, consistent risk reduction among patients receiving all types of agents (including nonaspirin antiplatelet agents). Protection was not apparent in patients taking anticoagulants.
authors.affiliation: Servicio de Aparato Digestivo, Hospital Clínico Zaragoza, Ciber Hepad, Zaragoza, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Lanas
authors.forename: Luis A
authors.initials: LA
authors.lastname: García-Rodríguez
authors.forename: Maria T
authors.initials: MT
authors.lastname: Arroyo
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.forename: Fernando
authors.initials: F
authors.lastname: Gomollón
authors.forename: Montserrat
authors.initials: M
authors.lastname: Forné
authors.forename: Sofía
authors.initials: S
authors.lastname: Aleman
authors.forename: David
authors.initials: D
authors.lastname: Nicolas
authors.forename: Faust
authors.initials: F
authors.lastname: Feu
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Pérez
authors.forename: Ana
authors.initials: A
authors.lastname: Borda
authors.forename: Manuel
authors.initials: M
authors.lastname: Castro
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Poveda
authors.forename: Juan
authors.initials: J
authors.lastname: Arenas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000925:Anticoagulants / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000627:therapeutic use*; D010438:Peptic Ulcer Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects*; D011446:Prospective Studies; D017494:Proton Pumps / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D004791:Enzyme Inhibitors; D009566:Nitrates; D010975:Platelet Aggregation Inhibitors; D017494:Proton Pumps