Skip to main content
Current Therapeutic Research, Clinical and Experimental logoLink to Current Therapeutic Research, Clinical and Experimental
. 2007 Mar;68(2):107–119. doi: 10.1016/j.curtheres.2007.03.003

Risk factors associated with NSAID-induced upper gastrointestinal bleeding resulting in hospital admissions: A cross-sectional, retrospective, case series analysis in valencia, spain

José Luis Marco 1,6, Pedro Amariles 2,3, Beatriz Boscá 4, Ana Castelló 5
PMCID: PMC3965967  PMID: 24678124

Abstract

Abstract

Background

NSAIDs are a significant cause of drug-related hospital admissions and deaths. The therapeutic effects of NSAIDs have been associated with the risk for developing adverse events, mainly in the gastrointestinal tract.

Objectives

The focus of this study was to identify the most common risk factors associated with NSAID-induced upper gastrointestinal bleeding (UGIB) resulting in hospital admissions. A secondary end point was the relationship between use of gastroprotective treatment and relevant risk factors to NSAID-induced UGIB in the selected population.

Methods

This study was a cross-sectional, retrospective, case-series analysis of NSAID-induced UGIB resulting in hospital admission to the Requena General Hospital, Valencia, Spain, occurring from 1997 to 2005. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify UGIB admissions associated with NSAIDs. To estimate the probability of association between UGIB and the use of NSAIDs, the Naranjo adverse drug reaction probability was used. Patients were categorized as high-risk to develop UGIB if they met ≥1 of the following risk criteria (relevant risk factors): aged ≥65 years (age risk factor); peptic ulcer disease or NSAID gastropathy occurring in the year before their hospital admission (history risk factor); and concomitant use of other NSAIDs, systemic corticoids, oral anticoagulants, or platelet aggregation inhibitors (concomitant medication risk factor). Patients were categorized as candidates to use gastroprotections if they met ≥1 of the relevant risk factors. Patients were categorized as users of gastroprotective treatment if they used proton pump inhibitors, histamine H2-receptor antagonists, or misoprostol at hospital admission.

Results

This study comprised 209 cases of NSAID-induced UGIB (129 men, 80 women: mean [SD] age, 71.5 [13.8] years; 128 [61.2%] receiving acetyl salicylic acid [ASA], with 72 [34.4%] receiving low-dose [80–325 mg] ASA). Prevalence of relevant risk factors for UGIB were as follows: age, 158 (75.6%) patients; history, 37 (17.7%); and concomitant medication, 35 (16.7%). One hundred seventy-eight (85.2%) patients met ≥1 criterion for using a gastroprotective agent; 28 (15.6%) were actually using one. Only the history risk factor was significantly associated with the use of gastroprotective treatment (P = 0.007; odds ratio = 3.17).

Conclusions

In this study of NSAID-induced UGIB resulting in hospital admission, age was the most common risk factor. However, this criterion was not associated with the use of gastroprotective agents. A large number of cases were associated with the use of ASA, primarily in those receiving low doses. A significant lack of gastroprotective agent use was observed in patients who met the criteria to use them.

Key Words: nonsteroidal anti-inflammatory drugs, upper gastrointestinal bleeding, hospital admissions, elderly, risk factors

Full Text

The Full Text of this article is available as a PDF (124.7 KB).

References

  • 1.Marco JL, Boscá B, San Martín MD. Ingresos hospitalarios por PRM en el Hospital General de Requena (1997–2000) Pharm Care Esp. 2002;4:286–299. [Google Scholar]
  • 2.Tarone RE, Blot WJ, McLaughlin JK. Nonselective nonaspirin nonsteroidal anti-inflammatory drugs and gastrointestinal bleeding: Relative and absolute risk estimates from recent epidemiologic studies. Am J Ther. 2004;11:17–25. doi: 10.1097/00045391-200401000-00007. [DOI] [PubMed] [Google Scholar]
  • 3.Ministerio de Salud y Consumo Grupos terapéuticos y principios activos de may or consumo en el Sistema Nacional de Salud durante 2003. Inf Ter Sist Nac de Salud. 2004;28:121–124. [Google Scholar]
  • 4.American Society of Health-System Pharmacists ASHP therapeutic position statement on the safe use of oral nonprescription analgesics. Am J Health Syst Pharm. 1999;56:1126–1131. doi: 10.1093/ajhp/56.11.1126. [DOI] [PubMed] [Google Scholar]
  • 5.Marco JL, Boscá B. Ingresos hospitalarios por hemorragia digestiva alta asociada a especialidades farmacéuticas publicitarias. Pharm Care Esp. 2003;5:112–113. [Google Scholar]
  • 6.Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med. 1998;105:31S–38S. doi: 10.1016/s0002-9343(98)00072-2. [DOI] [PubMed] [Google Scholar]
  • 7.Aalykke C, Lauritsen K. Epidemiology of NSAID-related gastroduodenal mucosal injury. Best Pract Res Clin Gastroenterol. 2001;15:705–722. doi: 10.1053/bega.2001.0230. [DOI] [PubMed] [Google Scholar]
  • 8.Derry S, Loke YK. Risk of gastrointestinal hemorrhage with long term use of aspirin: Meta-analysis. BMJ. 2000;321:1183–1187. doi: 10.1136/bmj.321.7270.1183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Lanas A, Perez-Aisa MA, Feu F. A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal antiinflammatory drug use. Am J Gastroenterol. 2005;100:1685–1693. doi: 10.1111/j.1572-0241.2005.41833.x. for the Investigators of the Asociation Española de Gastroenterología. [DOI] [PubMed] [Google Scholar]
  • 10.Higham J, Kang JY, Majeed A. Recent trends in admissions and mortality due to peptic ulcer in England: Increasing frequency of hemorrhage among older subjects. Gut. 2002;50:460–464. doi: 10.1136/gut.50.4.460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Laine L. The role of proton pump inhibitors in NSAID-associated gastropathy and upper gastrointestinal symptoms. Rev Gastroenterol Disord. 2003;3(Suppl 4):S30–S39. [PubMed] [Google Scholar]
  • 12.http://www.prodigy.nhs.uk/nonsteroidal_anti_inflammatory_drugs_nsaids/extended_information/management_issues
  • 13.Laine L, Bombardier C, Hawkey C. Stratifying the risk of NSAID-related upper gastrointestinal clinical events: Results of a double-blind outcomes study in patients with rheumatoid arthritis. Gastroenterology. 2002;123:1006–1012. doi: 10.1053/gast.2002.36013. [DOI] [PubMed] [Google Scholar]
  • 14.Greenwald DA. Aging, the gastrointestinal tract, and risk of acid-related disease. Am J Med. 2004;117(Suppl 5A):8S–13S. doi: 10.1016/j.amjmed.2004.07.019. [DOI] [PubMed] [Google Scholar]
  • 15.Lanas A, Martin-Mola E, Ponce J. Clinical strategy to prevent the gastrointestinal adverse effects of nonsteroidal anti-inflammatory agents [in Spanish] Gastroenterol Hepatol. 2003;26:485–502. doi: 10.1016/s0210-5705(03)70400-2. [DOI] [PubMed] [Google Scholar]
  • 16.Weil J, Langman MJ, Wainwright P. Peptic ulcer bleeding: Accessory risk factors and interactions with non-steroidal anti-inflammatory drugs. Gut. 2000;46:27–31. doi: 10.1136/gut.46.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Knijff-Dutmer EA, Schut GA, van de Laar MA. Concomitant coumarin-NSAID therapy and risk of bleeding. Ann Pharmacother. 2003;37:12–16. doi: 10.1345/aph.1C157. [DOI] [PubMed] [Google Scholar]
  • 18.Ng FH, Wong SY, Chang CM. High incidence of clopidogrel-associated gastrointestinal bleeding in patient with previous peptic ulcer disease. Aliment Pharmacol Ther. 2003;18:443–449. doi: 10.1046/j.1365-2036.2003.01693.x. [DOI] [PubMed] [Google Scholar]
  • 19.Ettinger B, Pressman A, Schein J. Clinic visits and hospital admissions for care of acid-related upper gastrointestinal disorders in women using alendronate for osteoporosis. Am J Manag Care. 1998;4:1377–1382. [PubMed] [Google Scholar]
  • 20.Lazzaroni M, Bianchi-Porro G. Prophylaxis and treatment of non-steroidal anti-inflammatory drug-induced upper gastrointestinal side-effects. Digest Liver Dis. 2001;33(Suppl 2):S44–S58. doi: 10.1016/s1590-8658(01)80158-4. [DOI] [PubMed] [Google Scholar]
  • 21.Cryer B. Gastrointestinal safety of low-dose aspirin. Am J Manag Care. 2002;8(Suppl 22):S701–S708. [PubMed] [Google Scholar]
  • 22.Moore RA, Derry S, Phillips CJ, McQuay HJ. Nonsteroidal anti-inflammatory drugs (NSAIDs), cyxlooxygenase-2 selective inhibitors (coxibs) and gastrointestinal harm: Review of clinical trials and clinical practice. BMC Musculoskelet Disord. 2006;7:79. doi: 10.1186/1471-2474-7-79. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Hooper L, Brown TJ, Elliott R. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: Systematic review. BMJ. 2004;329:948. doi: 10.1136/bmj.38232.680567.EB. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Rostom A, Dube C, Wells G. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2002;4 doi: 10.1002/14651858.CD002296. CD002296. [DOI] [PubMed] [Google Scholar]
  • 25.Dubois RW, Melmed GY, Henning JM, Bernal M. Risk of upper gastrointestinal injury and events in patients treated with cyclooxygenase (COX)-1/COX-2 nonsteroidal antiinflammatory drugs (NSAIDs), COX-2 selective NSAIDs, and gastroprotective cotherapy: An appraisal of the literature. J Clin Rheumatol. 2004;10:178–189. doi: 10.1097/01.rhu.0000128851.12010.46. [DOI] [PubMed] [Google Scholar]
  • 26.Ofman JJ, Badamgarav E, Henning JM. Utilization of nonsteroidal anti-inflammatory drugs and antisecretory agents: A managed care claims analysis. Am J Med. 2004;116:835–842. doi: 10.1016/j.amjmed.2004.02.028. [DOI] [PubMed] [Google Scholar]
  • 27.US Dept of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics (NCHS) NCHS; Hyattsville, Md: 2003. International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) [Google Scholar]
  • 28.Naranjo CA, Busto U, Sellers EM. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239–245. doi: 10.1038/clpt.1981.154. [DOI] [PubMed] [Google Scholar]
  • 29.Thomas J, Straus WL, Bloom BS. Over-the-counter nonsteroidal anti-inflammatory drugs and risk of gastrointestinal symptoms. Am J Gastroenterol. 2002;97:2215–2219. doi: 10.1111/j.1572-0241.2002.05974.x. [DOI] [PubMed] [Google Scholar]
  • 30.Lim CH, Heatley RV. Prospective study of acute gastrointestinal bleeding attributable to anti-inflammatory drug ingestion in the Yorkshire region of the United Kingdom. Postgrad Med J. 2005;81:252–254. doi: 10.1136/pgmj.2004.024885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Hartnell NR, Flanagan PS, MacKinnon NJ, Bakowsky V. Use of gastrointestinal preventive therapy among elderly persons receiving antiarthritic agents in Nova Scotia, Canada. Am J Geriatr Pharmacother. 2004;2:171–180. doi: 10.1016/j.amjopharm.2004.09.001. [DOI] [PubMed] [Google Scholar]
  • 32.Brown TJ, Hooper L, Elliott RA. A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: A systematic review with economic modelling. Health Technol Assess. 2006;10:1–183. doi: 10.3310/hta10380. [DOI] [PubMed] [Google Scholar]

Articles from Current Therapeutic Research, Clinical and Experimental are provided here courtesy of Elsevier

RESOURCES