Subject Category: Stomach

Am J Gastroenterol 2015; 110:684–689; doi:10.1038/ajg.2015.98; published online 21 April 2015

Peptic Ulcer Bleeding Risk. The Role of Helicobacter Pylori Infection in NSAID/Low-Dose Aspirin Users

C Sostres MD1, P Carrera-Lasfuentes PhD2, R Benito MD3, P Roncales4, M Arruebo MD4, M T Arroyo MD1, L Bujanda MD5, L A García-Rodríguez MD6 and A Lanas MD1,2,4

  1. 1Universitary Hospital Lozano Blesa, Gastroenterology Unit, Zaragoza, Spain
  2. 2CIBERehd, Madrid, Spain
  3. 3Universitary Hospital Lozano Blesa, Microbiology Unit, Zaragoza, Spain
  4. 4Health Science Institute of Aragon, Zaragoza, Spain
  5. 5Universitary Hospital of Donostia, San Sebastian, Spain
  6. 6CEIFE, Madrid, Spain

Correspondence: C. Sostres, MD, Universitary Hospital Lozano Blesa, Gastroenterology Unit, Calle San Juan Bosco 15, Zaragoza 50009, Spain. E-mail:

Received 1 October 2014; Accepted 1 February 2015
Advance online publication 21 April 2015





Helicobacter pylori (H. pylori) infection and NSAID/low-dose aspirin (ASA) use are associated with peptic ulcer disease. The risk of peptic ulcer bleeding (PUB) associated with the interaction of these factors remains unclear. The objective of this study was to determine the risk of PUB associated with the interaction between H. pylori infection and current nonsteroidal anti-inflammatory drugs (NSAIDs) or low-dose ASA use.



This was a case-control study of consecutive patients hospitalized because of PUB. Controls were matched by age, sex, and month of admission. H. pylori infection status was determined in all cases and controls by serology. Drug use was determined by structured questionnaire. Adjusted relative risk (RR) associated with different factors, and the interaction between NSAID/ASA and H. pylori infection was estimated by logistic regression analysis.



The study included 666 cases of PUB and 666 controls; 74.3% cases and 54.8% controls (RR: 2.6; 95% confidence interval (CI): 2.0–3.3) tested positive for H. pylori infection; 34.5% of cases had current NSAID use compared with 13.4% of controls (RR: 4.0; 95% CI: 3.0–5.4). Respective proportions for low-dose ASA use were 15.8 and 12%, respectively (RR: 1.9; 95% CI: 1.3–2.7). The RR of PUB for concomitant NSAID use and H. pylori infection suggested an additive effect (RR: 8.0; 95% CI: 5.0–12.8), whereas no interaction was observed with ASA use (RR: 3.5; 95% CI: 2.0–6.1).



NSAID, low-dose ASA use, and H. pylori infection are three independent risk factors for the development of PUB, but there were differences in the interaction effect between low-dose ASA (no interaction) or NSAID (addition) use and H. pylori infection, which may have implications for clinical practice in prevention strategies.