title: Risk of upper and lower gastrointestinal bleeding in patients taking nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants.
abstract: OBJECTIVE
  Treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose aspirin is associated with increased risk of upper gastrointestinal bleeding. There is little evidence on the risk of lower gastrointestinal bleeding with NSAIDs, antiplatelet agents (APAs), or anticoagulants. We aimed to quantify the relative risk (RR) of upper and lower gastrointestinal bleeding associated with use of NSAIDs, APAs, or anticoagulants.
  
  
  METHODS
  We performed a case-control study that used data collected from consecutive patients hospitalized for gastrointestinal bleeding (563 upper, mean age, 63.6 ± 16.7 years and 415 lower, mean age, 70.8 ± 13.8 years), confirmed by endoscopy or other diagnostic procedures. Unhospitalized patients were used as controls (n = 1008) and matched for age, hospital, and month of admission. Drug use was considered current when taken within 7 days or less before hospitalization. RRs and 95% confidence intervals (CIs) were estimated by unconditional logistic regression analysis.
  
  
  RESULTS
  Use of anticoagulants, low-dose aspirin, and other drugs (non-aspirin-APA, 82.3% thienopiridines) was associated with upper and lower gastrointestinal bleeding; the risk was 2-fold higher for anticoagulants (RR, 4.2; 95% CI, 2.9-6.2) than for low-dose aspirin (RR, 2.1; 95% CI, 1.4-3.3) or other non-aspirin-APA drugs (RR, 2.0; 95% CI, 1.6-2.6). NSAID use was also associated with increased risk of gastrointestinal bleeding and greater for upper (RR, 2.6; 95% CI, 2.0-3.5) than lower gastrointestinal bleeding (RR, 1.4; 95% CI, 1.0-1.9). Use of proton pump inhibitors was associated with reduced risk of upper, but not lower, gastrointestinal bleeding.
  
  
  CONCLUSIONS
  Anticoagulants, low-dose aspirin, NSAIDs, and other non-aspirin-APA drugs are associated with increased risk of upper and lower gastrointestinal bleeding. Use of anticoagulants appears to be the strongest risk factor for gastrointestinal bleeding.
authors.affiliation: Servicio de Aparato Digestivo, Hospital Clínico, University of Zaragoza, Zaragoza, Spain; CIBERehd, Barcelona, Spain. Electronic address: alanas@unizar.es.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Lanas
authors.affiliation: CIBERehd, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Carrera-Lasfuentes
authors.affiliation: Servicio de Aparato Digestivo, Hospital Clínico, University of Zaragoza, Zaragoza, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Arguedas
authors.affiliation: Servicio de Aparato Digestivo, Hospital Universiatrio Miguel Servet, Zaragoza, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: García
authors.affiliation: CIBERehd, Barcelona, Spain; Hospital Donostia, San Sebastian, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Bujanda
authors.affiliation: CIBERehd, Barcelona, Spain; Servicio de Aparato Digestivo, Corporació Sanitària Universitària, Sabadell, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Calvet
authors.affiliation: CIBERehd, Barcelona, Spain; Servicio de Aparato Digestivo, Hospital La Fe, Valencia, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: Ponce
authors.affiliation: Servicio de Aparato Digestivo, Hospital Costa del Sol, Marbella, Spain.
authors.forename: Ángeles
authors.initials: Á
authors.lastname: Perez-Aísa
authors.affiliation: CIBERehd, Barcelona, Spain; Gastroenterología, Hospital de Valme, Sevilla, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Castro
authors.affiliation: Servicio de Aparato Digestivo, Hospital Clínico, University of Zaragoza, Zaragoza, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Servicio de Aparato Digestivo, Hospital Clínico, University of Zaragoza, Zaragoza, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sostres
authors.affiliation: Centro Español de Investigación Farmacoepidemiológica, Madrid, Spain.
authors.forename: Luis A
authors.initials: LA
authors.lastname: García-Rodríguez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D018570:Risk Assessment
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D010975:Platelet Aggregation Inhibitors
keywords: Colon; Complication; Intestine; Peptic Ulcer; Side Effect; Small Bowel; Stomach