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Nonsteroidal Antiinflammatory Drugs Are Associated with Both Upper and Lower Gastrointestinal Bleeding

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Abstract

To evaluate the association between nonsteroidalantiinflammatory drug (NSAID) use and uppergastrointestinal bleeding (UGIB) and lowergastrointestinal bleeding (LGIB), we performed aprospective case-control study at a large inner-cityhospital over a 28-month period evaluating 461consecutive patients hospitalized for UGIB and 105 withLGIB. During the same period, 1895 in-patients evaluatedby our gastroenterology consultative service served ascontrols. At the time of initial evaluation, allpatients were asked about the use of any prescription orover-the-counter NSAID product within one week of admission. Endoscopic examination was performedin most patients with bleeding. NSAID use was almostequivalent in patients with UGIB and LGIB (60%) andsignificantly greater than controls [34%; P < 0.001; odds ratio (OR) 3.0; 95% CI, 2.4-3.6]. The age,race, and gender adjusted risk for LGIB associated withNSAID use was significant [adjusted OR (AOR) 2.6; 95% CI1.7-3.9], although less than UGIB (AOR 3.2; P = 0.34). The risk associated withdiverticular bleeding (N = 53, AOR 3.4; 95% CI 1.9-6.2)was higher than duodenal ulcer bleeding although notsignificantly (N = 97, AOR 3.0). We conclude that NSAIDuse is strongly associated with LGIB and from lesionsnot considered associated with mucosal ulceration suchas diverticulosis.

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REFERENCES

  1. Gabriel SE, Fehring RA: Trends in the utilization of nonsteroidal anti-inflammatory drugs in the United States, 1986–1990. J Clin Epidemiol 45:1041-1044, 1992

    Google Scholar 

  2. Barrier CH, Hirschowitz BI: Controversies in the detection and management of nonsteroidal anti-inflammatory drug-induced side effects of the upper gastrointestinal tract. Arthritis Rheum 32:926-932, 1989

    Google Scholar 

  3. Gibson T: Nonsteroidal anti-inflammatory drugs: another look. Br J Rheumatol 27:87-90, 1988

    Google Scholar 

  4. Hennekens CH: Final report on the aspirin component of the ongoing physicians' health study. N Engl J Med 321:129-135, 1989

    Google Scholar 

  5. Nyman I, Larsson H, Wallentin L: Prevention of serious cardiac events by low-dose aspirin in patients with silent myocardial ischaemia. Lancet 340:497-501, 1992

    Google Scholar 

  6. Adams HP Jr, Bendixen BH: Low-versus high-dose aspirin in prevention of ischemic stroke. Clin Neuropharmacol 16:485-500, 1993

    Google Scholar 

  7. Graham DY, White RH, Moreland LW, Shubert TT, Katz R, Jaszewski R, Tindall E, Triadafilopoulos G, Stromatt SC, Teoh LS, Misoprostol Study Group: Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Ann Intern Med 119:257-262, 1993

    Google Scholar 

  8. Graham DY, Agrawal NM, Roth SH: Prevention of NSAID-induced gastric ulcer with misoprostol: A multicenter, double-blind, placebo-controlled trial. Lancet 2:1277-1280, 1988

    Google Scholar 

  9. Agrawal NM, Roth S, Graham DY, White RH, Germain B, Brown JA, Stromatt SC: Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer: A randomized, controlled trial. Ann Intern Med 115:195-200, 1991

    Google Scholar 

  10. Ehsanulla RS, Page MC, Tildesley G, Wood JR: Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: Controlled trail of ranitidine. Br Med J 297:1017-1021, 1988

    Google Scholar 

  11. Robinson MG, Griffin JW Jr., Bowers J, Kogan FJ, Kogut DG, Lanza FL, Warner CW: Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal anti-inflammatory drugs. Dig Dis Sci 34:424-428, 1989

    Google Scholar 

  12. Lanza FL: A review of gastric ulcer and gastroduodenal injury in normal volunteers receiving aspirin and other non-steroidal anti-inflammatory drugs. Scand J Gastroenterol 24(suppl 163):24-31, 1989

    Google Scholar 

  13. Allison MC, Howatson AG, Torrance CJ, Lee FD, Russell RI: Gastrointestinal damage associated with the use of nonsteroidal anti-inflammatory drugs. N Engl J Med 327:749-754, 1992

    Google Scholar 

  14. Bjarnason I, Hayllar J, Macpherson AJ, Russell AJ: Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 104:1832-1847, 1993

    Google Scholar 

  15. Gibson GR, Whitacre EB, Ricotti CA: Colitis induced by nonsteroidal anti-inflammatory drugs. Report of four cases and review of the literature. Arch Intern Med 152:625-632, 1992

    Google Scholar 

  16. Hudson N, Wilkinson MJ, Swannell AJ, Steele RJ, Hawkey CJ: Ileo-caecal ulceration associated with the use of diclofenac slow release. Aliment Pharmacol Ther 7:197-200, 1993

    Google Scholar 

  17. Huber T, Ruchti C, Halter F: Nonsteroidal anti-inflammatory drug-induced colonic strictures: A case report. Gastroenterology 100:1119-1122, 1991

    Google Scholar 

  18. Gabriel SE, Jaakkimainen L, Bombardier C: Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med 115:787-796, 1991

    Google Scholar 

  19. Langman MJS, Coggon D, Spiegelhalter D: Analgesic intake and the risk of acute upper gastrointestinal bleeding. Am J Med 74:79-82, 1983

    Google Scholar 

  20. Caradoc-Davies TH: Non-steroidal anti-inflammatory drugs, arthritis, and gastrointestinal bleeding in elderly in-patients. Age Ageing 13:295-298, 1984

    Google Scholar 

  21. Collier DSJ, Pain JA: Non-steroidal anti-inflammatory drugs and peptic ulcer preparation. Gut 26:359-363, 1985

    Google Scholar 

  22. Bartle WR, Gupta AK, Lazor J: Non-steroidal anti-inflammatory drugs and gastrointestinal bleeding. Arch Intern Med 146:2365-2367, 1986

    Google Scholar 

  23. Somerville K, Faulkner G, Langman M: Non-steroidal anti-inflammatory drugs and bleeding peptic ulcer. Lancet 1:462-464, 1986

    Google Scholar 

  24. Armstrong CP, Blower AL: Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration. Gut 28:527-532, 1987

    Google Scholar 

  25. Carson JL, Strom BL, Soper KA, West SL, Morse ML: The association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal tract bleeding. Arch Intern Med 147:85-88, 1987

    Google Scholar 

  26. Beard K, Walker AM, Perera DR, Jick H: Nonsteroidal anti-inflammatory drugs and hospitalization for gastroesophageal bleeding in the elderly. Arch Intern Med 147:1621-1623, 1987

    Google Scholar 

  27. Levy M, Miller DR, Kaufman DW, Siskind V, Schwingz P, Rosenberg L, Strom B, Shapiro S: Major upper gastrointestinal tract bleeding. Arch Intern Med 148:281-285, 1988

    Google Scholar 

  28. Griffin MR, Ray WA, Schaffner W: Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med 109:359-363, 1988

    Google Scholar 

  29. Guess HA, West R, Strand LM, Helston D, Lydick KG, Bergman U: Fatal upper gastrointestinal hemorrhage or perforation among users and nonusers of nonsteroidal anti-inflammatory drugs in Saskatchewan, Canada 1983. J Clin Epidemiol 41:35-45, 1988

    Google Scholar 

  30. Faulkner G, Princhard P, Somerville K, Langman MJS: Aspirin and bleeding peptic ulcers in the elderly. BMJ 297:1311-1313, 1988

    Google Scholar 

  31. Beardon PHG, Brown SV, McDevitt DG: Gastrointestinal events in patients prescribed non-steroidal anti-inflammatory drugs: A controlled study using record linkage in Tayside. Q J Med 71:497-505, 1989

    Google Scholar 

  32. Bloom BS: Risk and cost of gastrointestinal side effects associated with nonsteroidal anti-inflammatory drugs. Arch Intern Med 149:1019-1022, 1989

    Google Scholar 

  33. Fries JF, Miller SR, Spitz PW, Williams CA, Hubert HB, Bloch DA: Toward an epidemiology of gastropathy associated with nonsteroidal anti-inflammatory drug use. Gastroenterology 96:647-655, 1989

    Google Scholar 

  34. Holman RAE, Davis M, Gough KR, Gartell P, Britton DC, Smith RB: Value of a centralised approach in the management of haematemesis and melaena: Experience in a district general hospital. Gut 31:504-508, 1990

    Google Scholar 

  35. Stodolnik E, Maurer R, Hoigne R, Hess T, Muller U, Amonn F, Halter F, Maibach R, Kunzi UP: Risk of acute upper gastrointestinal bleeding in patients with ulcerative disease and treatment with non-steroidal anti-inflammatory drugs NSAIDs). Eur J Clin Pharmacol 38:31-35, 1990

    Google Scholar 

  36. Holvoet J, Terriere L, Van Hee W, Fierens E, Hautekeete ML: Relation of upper gastrointestinal bleeding to non-steroidal anti-inflammatory drugs and aspirin: A case-control study. Gut 32:730-734, 1991

    Google Scholar 

  37. Laporte JR, Carne X, Vidal X, Morend V, Juan J, Catalan Countries Study on Upper Gastrointestinal Bleeding: Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs. Lancet 337:85-89, 1991

    Google Scholar 

  38. Kaufman DW, Kelly JP, Sheehan JE, Laszio A, Wihholm BE, Alfredsson L, Koff RS, Shapiro S: Nonsteroidal anti-inflammatory drug use in relation to major upper gastrointestinal bleeding. Clin Pharmacol Ther 53:485-494, 1993

    Google Scholar 

  39. Henry D, Dobson A, Turner C: Variability in the risk of major gastrointestinal complications from nonaspirin nonsteroidal anti-inflammatory drugs. Gastroenterology 105:1078-1088, 1993

    Google Scholar 

  40. Langman MJS, Weil J, Wainwright P, Lawson DH, Rawlins MD, Logan RFA, Murphy M, Vessey MP, Colin-Jones DG: Risks of bleeding peptic ulcer associated with individual nonsteroidal anti-inflammatory drugs. Lancet 343:1075-1078, 1994

    Google Scholar 

  41. Langman MJS, Morgan L, Worral A: Use of anti-inflammatory drugs by patients admitted with small or large bowel perforations and hemorrhage. BMJ 290:347-349, 1985

    Google Scholar 

  42. Lanas A, Sekar MC, Hirschowitz BI: Objective evidence of aspirin use in both ulcer and nonulcer upper and lower gastrointestinal bleeding. Gastroenterology 103:862-869, 1992

    Google Scholar 

  43. Holt S, Rigoglioso V, Sidhu M, Irshad M, Howden CW, Mainer M: Nonsteroidal anti-inflammatory drugs and lower gastrointestinal bleeding. Dig Dis Sci 38:1619-1623, 1993

    Google Scholar 

  44. Physicians Desk Reference for Non-Prescription Drugs. Medical Economics Data Co. Inc., Montvale, New Jersey, 1990

  45. SAS Institute: SAS User's Guide: Statistics, Version 5 ed. Cary, North Carolina, SAS Institute, 1985

    Google Scholar 

  46. Kleinbaum DG, Kupper LL, Morgenstern H: Epidemiologic Research: Principles and Quantitative Methods. Belmont, California, Lifetime Learning Publications, 1982

    Google Scholar 

  47. Greenberg RS, Kleinbaum DG: Mathematical modeling strategies for the analysis of epidemiologic research. Annu Rev Public Health 6:223-245, 1985

    Google Scholar 

  48. Greenland S: Modeling and variable selection in epidemiologic analysis. Am J Public Health 79:340-349, 1989

    Google Scholar 

  49. Peterson WL, Barnett CC, Smith HJ, Allen MH, Corbett DB: Routine early endoscopy in upper gastrointestinal-tract bleeding. N Engl J Med 304:925-929, 1981

    Google Scholar 

  50. Zuckerman GR, Cornette GL, Clouse RE, Harter HR: Upper gastrointestinal bleeding in patients with chronic renal failure. Ann Intern Med 102:588-592, 1985

    Google Scholar 

  51. Laine L: Upper gastrointestinal tract hemorrhage. West J Med 155:274-279, 1991

    Google Scholar 

  52. Caos A, Benner KG, Manier J, McCarthy DM, Blessing LD, Katon RM: Colonoscopy after golytely preparation in acute rectal bleeding. J Clin Gastroenterol 8:46-49, 1986

    Google Scholar 

  53. Leitman IM, Paull DE, Shires GT: Evaluation and management of massive lower gastrointestinal hemorrhage. Ann Surg 209:175-180, 1989

    Google Scholar 

  54. Jensen DM, Machicado GA: Diagnosis and treatment of severe hematochezia. The role of urgent colonoscopy after purge. Gastroenterology 95:1569-1574, 1988

    Google Scholar 

  55. Wilcox CM, Shalek KA, Cotsonis G: Striking prevalence of over-the-counter nonsteroidal anti-inflammatory drug use in patients with upper gastrointestinal hemorrhage. Arch Intern Med 154:42-46, 1994

    Google Scholar 

  56. Gabriel SE, Jaakkimainen L, Bombardier C: Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs: A meta-analysis. Ann Intern Med 115:787-796, 1991

    Google Scholar 

  57. Kurata JH, Abbey DE: The effect of chronic aspirin use on duodenal and gastric ulcer hospitalizations. J Clin Gastroenterol 12:260-266, 1990

    Google Scholar 

  58. Patrono C, Ciabattoni G, Patrignani P, Pugliese F, Filabozzi P, Catella F, Davi G, Forni L: Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation 72:1177-1184, 1985

    Google Scholar 

  59. Stampfer MJ, Jakubowski JA, Deykin D, Schafer AJ, Willet WC, Hennekensc H: Effect of alternate-day regular and enteric-coated aspirin on platelet aggregation, bleeding time, and thromboxane A2 levels in bleeding-time blood. Am J Med 81:400-404, 1986

    Google Scholar 

  60. Küster LJ, Frölich JC: Platelet aggregation and thromboxane release induced by arachidonic acid, collagen, ADP and platelet-activating factor following low dose acetylsalicylic acid in man. Prostaglandins 32:415-423, 1986

    Google Scholar 

  61. Suh O, Mettlin C, Petrelli NJ: Aspirin use, cancer, and polyps of the large bowel. Cancer 72:1171-1177, 1993

    Google Scholar 

  62. Peleg II, Lubin MF, Cotsonis GA, Clark WS, Wilcox CM: Long-term use of nonsteroidal antiinflammatory drugs and other chemopreventors and the risk of subsequent colorectal neoplasia. Dig Dis Sci 41:1319-1326, 1996

    Google Scholar 

  63. Hochberg MC: Association of nonsteroidal anti-inflammatory drugs with upper gastrointestinal disease: Epidemiologic and economic considerations. J Rheumatol 19(suppl 36):63-67, 1992

    Google Scholar 

  64. Klein WA, Krevsky B, Klepper L, Ljubich P, Niewiarowski TJ, Rothstein KD, Dabezies MA, Fisher RS: Nonsteroidal anti-inflammatory drugs and upper gastrointestinal hemorrhage in an urban hospital. Dig Dis Sci 38:2049-2055, 1993

    Google Scholar 

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Authors
  1. C. Mel Wilcox
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  2. Lorraine N. Alexander
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  3. George A. Cotsonis
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  4. W. Scott Clark
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Wilcox, C.M., Alexander, L.N., Cotsonis, G.A. et al. Nonsteroidal Antiinflammatory Drugs Are Associated with Both Upper and Lower Gastrointestinal Bleeding. Dig Dis Sci 42, 990–997 (1997). https://doi.org/10.1023/A:1018832902287

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