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Inappropriate Prevention of NSAID-Induced Gastrointestinal Events Among Long-Term Users in the Elderly

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Abstract

Although use of NSAIDs and aspirin (acetylsalicylic acid) is well known to be associated with gastrointestinal (GI) complications and potential mortality, these medications continue to be widely prescribed in the elderly. Age is a significant risk factor for NSAID-induced GI events; indeed, patients >75 years of age carry the highest risk and are similar in this respect to patients with a history of peptic ulcer. Prevention of NSAID-induced gastropathy is indicated in patients at risk. It is accepted that patients >60 years of age taking NSAIDs should participate in prevention strategies such as co-therapy with proton pump inhibitors (PPIs) or misoprostol, or use of cyclo-oxygenase (COX)-2 selective NSAIDs (also called coxibs). Although up to 33% of subjects with no risk factors who receive NSAIDs over-utilise GI preventive therapies, under-utilisation of gastroprotective therapy is more prevalent among those with risk factors, of which the most frequent is age. At least half of those at risk do not receive appropriate preventive therapy, either because they do not receive co-therapy with PPIs or misoprostol or are not treated with COX-2 selective NSAIDs, or because they receive co-therapy with antacids or histamine H2 receptor antagonists, which are not effective. Adherence to the prescribed preventive therapy is an additional problem for those who are prescribed a PPI or misoprostol. Over 30% of patients are non-adherent and the lowest rate of non-adherence is associated with the first NSAID prescription, which increases the risk of ulcer bleeding compared with those who are fully adherent. Predictors of nonadherence include long-term use of NSAIDs and a high average daily dose of NSAIDs. Predictors of adherence include a history of upper gastrointestinal events, anticoagulant use, rheumatological disease and use of low-dose salicylates, among others. Another important aspect is self-medication; this is common in the elderly, who also have several risk factors for GI complications, and may be a factor in over one-third of all NSAID-related complications. In summary, aging is a key risk factor for GI complications in patients taking NSAIDs. Appropriate prevention strategies should be used in the elderly and those at risk; special attention should be paid to compliance and self-medication.

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References

  1. Dubois RW, Melmed GY, Henning JM, et al. Guidelines for the appropriate use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitors in patients requiring chronic anti-inflammatory therapy. Aliment Pharmacol Ther 2004; 19: 197–208

    Article  PubMed  CAS  Google Scholar 

  2. Kimmey MB, Lanas A. Review article: appropriate use of proton pump inhibitors with traditional nonsteroidal anti-inflammatory drugs and COX-2 selective inhibitors. Aliment Pharmacol Ther 2004; 19Suppl. 1: 60–5

    Article  PubMed  CAS  Google Scholar 

  3. Sturkenboom MCJM, Burke TA, Dieleman JP, et al. Underutilization of preventive strategies in patients receiving NSAIDs. Rheumatology 2003; 42Suppl. 3: 23–31

    Google Scholar 

  4. Laine L. Approaches to NSAID use in the high risk patient. Gastroenterology 2001; 120: 594–606

    Article  PubMed  CAS  Google Scholar 

  5. Brun J, Jones R. Non-steroidal anti-inflammatory drug-associated dyspepsia: the scale of the problem. Am J Med 2001; 110: 12S–3S

    Article  PubMed  CAS  Google Scholar 

  6. Armstrong CP, Blower AL. Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration. Gut 1987; 28: 527–32

    Article  PubMed  CAS  Google Scholar 

  7. Langman MJ, Weil J, Wainwright P, et al. Risks of bleeding peptic ulcer associated with individual non-steroidal anti-inflammatory drugs. Lancet 1994; 343: 1075–8

    Article  PubMed  CAS  Google Scholar 

  8. Allison MC, Howatson AG, Torrance CJ, et al. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 1992; 327(11): 749–54

    Article  PubMed  CAS  Google Scholar 

  9. Lanas A, Serrano P, Bajador E, et al. Evidence of aspirin use in both upper and lower gastrointestinal perforation. Gastroenterology 1997; 112: 683–9

    Article  PubMed  CAS  Google Scholar 

  10. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999; 340: 1888–99

    Article  PubMed  CAS  Google Scholar 

  11. Lanas A, Perez-Aisa MA, Feu F, et al. 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(8): 1685–93

    Article  PubMed  CAS  Google Scholar 

  12. Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995; 123(4): 241–9

    PubMed  CAS  Google Scholar 

  13. Laine L, Bombardier C, Hawkey CJ, et al. 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(4): 1006–12

    Article  PubMed  CAS  Google Scholar 

  14. Lanas A, Hunt R. Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits and risks of therapeutic strategies. Ann Med 2006; 38(6): 415–28

    Article  PubMed  CAS  Google Scholar 

  15. Lanas A. Cost stratification of nonsteroidal anti-inflammatory drug-associated gastrointestinal side effects. Med Clin (Barc) 2000; 114Suppl. 3: 46–53

    Google Scholar 

  16. Kaufman DW, Kelly JP, Rosenberg L, et al. Recent patterns of medication use in the ambulatory adult population of the United States. JAMA 2002; 287: 337–44

    Article  PubMed  Google Scholar 

  17. Gray SL, Sager M, Lestico MR, et al. Adverse drug events in hospitalized elderly. J Gerontol Med Sci 1998; 53A: M59–63

    Article  Google Scholar 

  18. Gurwitz JH, Field TS, Harrold LR, et al. Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA 2003; 289: 1107–16

    Article  PubMed  Google Scholar 

  19. Pilotto A, Franceschi M, Vitale D, et al. Drug use by the elderly in general practice: effects on upper gastrointestinal symptoms. Eur J Clin Pharmacol 2006; 62: 65–73

    Article  PubMed  Google Scholar 

  20. Lanas A, Bajador E, Serrano P, et al. Nitrovasodilators, lowdose aspirin, nonsteroidal anti-inflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 2000; 343: 834–9

    Article  PubMed  CAS  Google Scholar 

  21. Lanas A, Garcia-Rodriguez L-A, Arroyo M-T, et al. Risk of upper gastrointestinal ulcer bleeding associated with selective COX-2 inhibitors, traditional non-aspirin NSAIDs, aspirin, and combinations. Gut 2006 Dec; 55(12): 1731–8

    Article  PubMed  CAS  Google Scholar 

  22. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. JAMA 2000; 284(10): 1247–55

    Article  PubMed  CAS  Google Scholar 

  23. Singh G, Fort JG, Goldstein JL, et al. Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-I study. Am J Med 2006; 119(3): 255–66

    Article  PubMed  CAS  Google Scholar 

  24. Rostom A, Wells G, Tugwell P, et al. Prevention of chronic NSAID induced upper gastrointestinal toxicity. Cochrane Database Syst Rev 2000; (3): CD002296

    Google Scholar 

  25. Taha AS, Hudson N, Hawkey CJ, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs. N Engl J Med 1996; 334(22): 1435–9

    Article  PubMed  CAS  Google Scholar 

  26. ten Wolde S, Dijkmans BA, Janssen M, et al. High-dose ranitidine for the prevention of recurrent peptic ulcer disease in rheumatoid arthritis patients taking NSAIDs. Aliment Pharmacol Ther 1996; 10(3): 347–51

    Article  PubMed  Google Scholar 

  27. Hudson N, Taha AS, Russell RI, et al. Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration. Gastroenterology 1997; 112(6): 1817–22

    Article  PubMed  CAS  Google Scholar 

  28. Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Eng J Med 2002; 347(26): 2104–10

    Article  CAS  Google Scholar 

  29. Lai KC, Chu KM, Hui WM, et al. Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. Am J Med 2005; 118(11): 1271–8

    Article  PubMed  CAS  Google Scholar 

  30. Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology 2004; 127(4): 1038–43

    Article  PubMed  CAS  Google Scholar 

  31. Hooper L, Brown TJ, Elliott R, et al. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ 2004; 329(7472): 948

    Article  PubMed  CAS  Google Scholar 

  32. Hawkey C, Talley NJ, Yeomans ND, et al. Improvements with esomeprazole in patients with upper gastrointestinal symptoms taking non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors. Am J Gastroenterol 2005; 100(5): 1028–36

    Article  PubMed  CAS  Google Scholar 

  33. Graham DY, Agrawal NM, Campbell DR, et al. Ulcer prevention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs lansoprazole. Arch Intern Med 2002; 162(2): 169–75

    Article  PubMed  CAS  Google Scholar 

  34. Laine L, Wogen J, Yu H. Gastrointestinal health care resource utilization with chronic use of COX-2-specific inhibitors versus traditional NSAIDs. Gastroenterology 2003; 125(2): 389–95

    Article  PubMed  CAS  Google Scholar 

  35. Chan FKL, Wong VW, Suen BY, et al. Proton pump inhibitor plus a COX-2 inhibitor for the prevention of recurrent ulcer bleeding in patients with arthritis: a double blind, randomized trial [abstract no. A732]. Gastroenterology 2006; 130 (4 Pt 2): 133

    Google Scholar 

  36. Lanas A. Economic analysis of strategies in the prevention of non-steroidal anti-inflammatory drug-induced complications in the gastrointestinal tract. Aliment Pharmacol Ther 2004; 20(3): 321–31

    Article  PubMed  CAS  Google Scholar 

  37. Lanas A, Fuentes J, Benito R, et al. Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 2002; 16(4): 779–86

    Article  PubMed  CAS  Google Scholar 

  38. Goldstein JL, Huang B, Amer F, et al. Ulcer recurrence in highrisk patients receiving nonsteroidal anti-inflammatory drugs plus low-dose aspirin: results of a post HOC subanalysis. Clin Ther 2004; 26(10): 1637–43

    Article  PubMed  CAS  Google Scholar 

  39. Rahme E, Bardou M, Dasgupta K, et al. Hospitalization for gastrointestinal bleeding associated with non-steroidal anti-inflammatory drugs among elderly patients using low-dose aspirin: a retrospective cohort study. Rheumatology 2007; 46(2): 265–72

    Article  PubMed  CAS  Google Scholar 

  40. Goldstein JL, Aisenberg J, Berger M, et al. Effect of concomitant (81mg qd) on incidence of gastric and/or duodenal ulcers in healthy subjects taking celecoxib or naproxen: a randomized placebo-controlled trial [abstract no. A562]. Gastroenterology 2006; 130 (4 Pt 2): 81

    Google Scholar 

  41. Schnitzer TJ, Burmester GR, Mysler E, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet 2004; 364(9435): 665–74

    Article  PubMed  CAS  Google Scholar 

  42. Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in pepticulcer disease: a meta-analysis. Lancet 2002; 359: 14–22

    Article  PubMed  CAS  Google Scholar 

  43. Ji KY, Hu FL. Interaction or relationship between Helicobacter pylori and non-steroidal anti-inflammatory drugs in upper gastrointestinal diseases. World J Gastroenterol 2006; 12: 3789–92

    PubMed  CAS  Google Scholar 

  44. Pilotto A, Franceschi M, Leandro G, et al. Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal antiinflammatory drugs. Aliment Pharmacol Ther 2004; 20(10): 1091–7

    Article  PubMed  CAS  Google Scholar 

  45. Pilotto A, Franceschi M, Leandro G, et al. The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs. Aging Clin Exp Res 2003; 15(6): 494–9

    PubMed  CAS  Google Scholar 

  46. 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 1991; 115:787–96

    PubMed  CAS  Google Scholar 

  47. Smalley WE, Griffin MR. The risks and costs of upper gastrointestinal disease attributable to NSAIDs. Gastroenterol Clin North Am 1996; 25: 373–96

    Article  PubMed  CAS  Google Scholar 

  48. Abraham NS, El-Serag HB, Johnson ML, et al. National adherence to evidence-based guidelines for the prescription of nonsteroidal anti-inflammatory drugs. Gastroenterology 2005; 126: 1171–8

    Article  Google Scholar 

  49. Pietzsch M, Theuer S, Haase G, et al. Results of systematic screening for serious gastrointestinal bleeding associated with NSAIDs in Rostock hospitals. Int J Clin Pharmacol Ther 2002; 40: 111–5

    PubMed  CAS  Google Scholar 

  50. van Dijk KN, ter Huurne K, de Vries CS, et al. Prescribing of gastroprotective drugs among elderly NSAID users in The Netherlands. Pharm World Sci 2002; 24(3): 100–3

    Article  PubMed  Google Scholar 

  51. Arboleya LR, de la Figuera E, Soledad Garcia M, et al. Management pattern for patients with osteoarthritis treated with traditional non-steroidal anti-inflammatory drugs in Spain prior to introduction of coxibs. Curr Med Res Opin 2003; 19(4): 278–87

    Article  PubMed  CAS  Google Scholar 

  52. Sturkenboom MCJM, Burke TA, Tangelder MJD, et al. Adherence to proton pump inhibitors or H2-receptor antagonists during the use of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2003; 18: 1137–47

    Article  PubMed  CAS  Google Scholar 

  53. Hartneil NR, Flanagan PS, MacKinnon NJ, et al. Use of gastrointestinal preventive therapy among elderly persons receiving antiarthritic agents in Nova Scotia, Canada. Am J Geriatr Pharmacother 2004; 2(3): 171–80

    Article  Google Scholar 

  54. Pilotto A, Franceschi M, Vitale DF, et al. Upper gastrointestinal symptoms and therapies in elderly out-patients, users of nonselective NSAIDs or coxibs. Aliment Pharmacol Ther 2005; 22(2): 147–55

    Article  PubMed  CAS  Google Scholar 

  55. Teeling M, Bennett K, Feely J. Have COX-2 inhibitors influenced the co-prescription of anti-ulcer drugs with NSAIDs?. Br J Clin Pharmacol 2004; 57(3): 337–43

    Article  PubMed  Google Scholar 

  56. Silvani MC, Motola M, Poluzzi E, et al. Gastrointestinal problems and concomitant medication in NSAID users: additional findings from a questionnaire-based survey in Italy. Eur J Clin Pharmacol 2006; 62: 235–41

    Article  PubMed  Google Scholar 

  57. Hur C, Chan AT, Tramontano AC, et al. Coxibs versus combination NSAID and PPI therapy for chronic pain: an exploration of the risks, benefits, and costs. Ann Pharmacother 2006; 40(6): 1052–63

    Article  PubMed  CAS  Google Scholar 

  58. Motola D, Vaccheri A, Silvani MC, et al. Pattern of NSAID use in the Italian general population: a questionnaire-based survey. Eur J Clin Pharmacol 2004; 60(10): 731–8

    Article  PubMed  Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this review.

Dr Lanas has been a consultant for Nicox and Pfizer, has received speaker’s honoraria from AstraZeneca, Pfizer, Merck and Takeda, and was an investigator for the APPROVe (Adenomatous Polyp Prevention on Vioxx) trial of rofecoxib. The authors have no other potential conflicts of interest that are directly relevant to the content of this review.

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  1. Service of Digestive Diseases, University Hospital, Instituto Aragones de Ciencias de la Salud (CIBER HEPAD), University of Zaragoza, Zaragoza, Spain

    Angel Lanas & Angel Ferrandez

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  1. Angel Lanas
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Correspondence to Angel Lanas.

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Lanas, A., Ferrandez, A. Inappropriate Prevention of NSAID-Induced Gastrointestinal Events Among Long-Term Users in the Elderly. Drugs Aging 24, 121–131 (2007). https://doi.org/10.2165/00002512-200724020-00004

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