Journal of Gastroenterology

, Volume 45, Issue 9, pp 944–951

Association between adherence to evidence-based guidelines for the prescription of non-steroidal anti-inflammatory drugs and the incidence of gastric mucosal lesions in Japanese patients

  • Hidetaka Tsumura
  • Tsuyoshi Fujita
  • Isamu Tamura
  • Yoshinori Morita
  • Masaru Yoshida
  • Takashi Toyonaga
  • Hidekazu Mukai
  • Hideto Inokuchi
  • Hiromu Kutsumi
  • Takeshi Azuma
Original Article—Alimentary Tract

Abstract

Objective

Recently, guidelines for the treatment and prevention of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs) were established. This study investigated the association between the current adherence to the guidelines and the incidence of gastric mucosal lesions caused by NSAIDs.

Methods

This study included 254 NSAIDs users (128 regular and 126 on-demand users) who had undergone upper gastrointestinal endoscopy. The patients were characterized as high risk based on the following: age 65 years or older, history of peptic ulcers, concurrent use of corticosteroids or anticoagulants, and high-dose NSAIDs use. Adherence was defined as the prescription of NSAIDs with proton pump inhibitors, prostaglandin analogues, or high-dose histamine 2 receptor antagonists in high-risk NSAIDs user. The severity of gastric mucosal lesions was evaluated using the modified LANZA score (MLS).

Results

Seventy-nine (61.7%) of the regular NSAIDs users and 65 (51.6%) of the on-demand NSAIDs users met our definition of high-risk patients. Adherence in the regular NSAIDs users and on-demand NSAIDs users was 25 (31.7%) and 16 (24.6%), respectively. The incidence of gastric mucosal lesions (MLS ≧ 1) was significantly higher in the nonadherence group than in the adherence group for both regular NSAIDs users (59.3 vs. 28.0%, P = 0.01) and on-demand NSAIDs users (63.3 vs. 25.0%, P = 0.01). Gastric ulcers in the regular NSAIDs users were more frequently observed in the nonadherence group than in the adherence group (29.6 vs. 4.0%, P < 0.01).

Conclusion

Nonadherence was associated with a high prevalence of NSAIDs-induced gastric mucosal lesions.

Keywords

NSAIDs-guideline Gastric mucosal lesions Adherence 

References

  1. 1.
    Clinard Francois, Bardou Marc, Sgro Catherine, Lefevre Nathalie, Raphael Francis, Paille Francois, et al. Non-steroidal anti-inflammatory and cytoprotective drug co-prescription in general practice. Eur J Clin Pharmacol. 2001;57:737–43.CrossRefPubMedGoogle Scholar
  2. 2.
    Taha AS, Hudson N, Hawkey CJ, Swannell AJ, Trye PN, Cottrell J, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal anti-inflammatory drugs. N Engl J Med. 1996;334:1435–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Weil J, Langman MJ, Wainwright P, Lawson DH, Rawlins M, Logan RF, et al. Peptic ulcer bleeding: accessory risk factors and interactions with non-steroidal anti-inflammatory drugs. Gut. 2000;46:27–31.CrossRefPubMedGoogle Scholar
  4. 4.
    Shiokawa Y, Nobenaga T, Saitoh T, Asaji S, Ogawa A. Epidemiological study on upper digestive injuries by non-steroidal anti-inflammatory drugs. J Jpn Rheum Assoc. 1991;31:96–111 (in Japanese).Google Scholar
  5. 5.
    Gabriel SE, Jaakkinmainen 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.PubMedGoogle Scholar
  6. 6.
    Bellary SV, Isaacs PE, Lee FI. Upper gastrointestinal lesions in elderly patients presenting for endoscopy; relevance of NSAID usage. Am J Gastroenterol. 1991;86:961–4.PubMedGoogle Scholar
  7. 7.
    Fries JF, Williams CA, Bloch DA, Michel DA. Nonsteroidal anti-inflammatory drug-associated gastropathy: incidence and risk factor models. Am J Med. 1991;91:213–22.CrossRefPubMedGoogle Scholar
  8. 8.
    Lanza FL, Chan FK, Quigley EM. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104:728–38.CrossRefPubMedGoogle Scholar
  9. 9.
    Recommendation for the medical management of osteoarthritis of the hip and knee. 2000 update. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Arthritis Rheum 2000;43:1905–15.Google Scholar
  10. 10.
    Lanza FL. A guideline for the treatment and prevention of NSAID-induced ulcers: members of the ad hoc committee on practice parameters of the American college of gastroenterology. Am J Gastroenterol. 1998;93(11):2037–46.CrossRefPubMedGoogle Scholar
  11. 11.
    MacLean CH. Quality indicators for the management of osteoarthritis in vulnerable elders. Ann Intern Med. 2001;135:711–21.PubMedGoogle Scholar
  12. 12.
    Abrahama NS, El-Serag HB, Johnson ML, Hartman C, Richardson P, Ray WA, et al. National adherence to evidence-based guidelines for the prescription of nonsteroidal anti-inflammatory drugs. Gastroenterology. 2005;129(4):1171–8.CrossRefGoogle Scholar
  13. 13.
    Smalley WE, Griffin MR. The risks and costs of upper gastrointestinal disease attributable to NSAIDs. Gastroenterol Clin North Am. 1996;25(2):373–96.CrossRefPubMedGoogle Scholar
  14. 14.
    Hernandez-Diaz S, Rodriguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation. Arch Intern Med. 2000;160:2093–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Moens HJ, Van Croonenborg JJ, Al MJ, van den Bemt PM, Lourens J, Numans ME, et al. Guideline: ‘NSAID use and the prevention of gastric damage’. Ned Tijdschr Geneeskd. 2003;148:604–8.Google Scholar
  16. 16.
    Wofe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Eng J Med. 1999;340:1888–99.CrossRefGoogle Scholar
  17. 17.
    van Soest EM, Sturkenboom MC, Dieleman JP, Verhamme KM, Siersema PD, Kuipers EJ. Adherence to gastroprotection and the risk of NSAID-related upper gastrointestinal ulcers and haemorrhage. Aliment Pharmacol Ther. 2007;26(2):265–75.CrossRefPubMedGoogle Scholar
  18. 18.
    Lanza FL, Fakouhi D, Rubin A, Davis RE, Rack MF, Nissen C, et al. A double-blind placebo-controlled comparison of the efficacy and safety of 50, 100, and 200 micrograms of misoprostol q.i.d. in the prevention of ibuprofen-induced gastric and duodenal mucosal lesions and symptoms. Am J Gastroenterol. 1989;84:633–6.PubMedGoogle Scholar
  19. 19.
    Targownik LE, Metge CJ, Leung S, Chateau DG. The relative efficacies of gastroprotective strategies in chronic users of nonsteroidal anti-inflammatory drugs. Gastroenterology. 2008;134:937–44.CrossRefPubMedGoogle Scholar
  20. 20.
    Lanza FL. A double-blind study of prophylactic effect of misoprostol on lesions of gastric and duodenal mucosa induced by oral administration of tolmetin in healthy subjects. Dig Dis Sci. 1986;31:131–6.CrossRefGoogle Scholar
  21. 21.
    Hawkey C, Talley NJ, Yeomans ND, Jones R, Sung JJ, Langstrom G, 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;100:1028–36.CrossRefPubMedGoogle Scholar
  22. 22.
    Hooper L, Brown TJ, Elliott R, Payne K, Roberts C, Symmons D. The effectiveness of five strategies for the prevention of gastrointestinal toxicity induced by non-steroidal anti-inflammatory drugs: systematic review. BMJ. 2004;329:948.CrossRefPubMedGoogle Scholar
  23. 23.
    Rostom A, Dube C, Wells G, Tugwell P, Welch V, Jolicoeur E, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2002;(4):CD002296.Google Scholar
  24. 24.
    Scheiman JM, Yeomans ND, Talley NJ, Vakil N, Chan FK, Tulassay Z, et al. Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol. 2006;101(4):701–10.CrossRefPubMedGoogle Scholar
  25. 25.
    Tsumura H, Tamura I, Tanaka H, Chinzei R, Ishida T, Masuda A, et al. Prescription of non steroidal anti-inflammatory drugs and co-prescribed drugs for mucosal protection: analysis of the present status based on questionnaires obtained from orthopedists in Japan. Intern Med. 2007;46:927–31.CrossRefPubMedGoogle Scholar
  26. 26.
    EBM ni motozuku ikaiyou shinnryou gaidolain dai2han. NSAID kaiyou yobou. in EBM ni motozuku ikaiyou shinnryou gaidolain. Jihou, 2007 (in Japanese).Google Scholar
  27. 27.
    Schnitzer TJ, American College of Rheumatology. Update of ACR guidelines for osteoarthritis: role of the coxibs. J Pain Symptom Manage. 2002;23(Suppl 4):S24–30.CrossRefPubMedGoogle Scholar
  28. 28.
    Sorensen R, Hansen ML, Abildstrom SZ, Hvelplund A, Torp-Pedersen C, Gislason GH. Risk of bleeding in patients with acute myocardial infarction treated with different combinations of aspirin, clopidogrel, and vitamin K antagonists in Demark: a retrospective analysis of nationwide registry data. Lancet. 2009;374:1967–74.CrossRefPubMedGoogle Scholar
  29. 29.
    Naito Y, Yoshikawa T, Iinuma S, Yagi N, Matsuyama K, Boku Y, et al. Rebamipide protects against indomethacin-induced gastric mucosal injury in healthy volunteers in a double-blind, placebo-controlled study. Dig Dis Sci. 1998;43:83–9.Google Scholar
  30. 30.
    Lanza FL, Royer GL, Nelson RS, Chen TT, Sechman CE, Rack MF. A comparative endoscopic evaluation of the damaging effects of nonsteroidal anti-inflammatory agents on the gastric and duodenal mucosa. Am J Gatroenterol. 1981;75:17–21.Google Scholar
  31. 31.
    Kobayashi K, Mizushima Y, Yanagawa A, Kasukawa R, Ito J, Koshino T, et al. Prophylactic effects ranitidine, a H2 receptor antagonist, on gastric and duodenal lesions induced by nonsteroidal anti-inflammatory agents. J Adult Dis. 1990;20:253–64 (in Japanese).Google Scholar
  32. 32.
    Robinson MG, Griffin JW, Bowers J, Kogan FJ, Kogut DG, Lanza FL, et al. Effect on ranitidine on gastroduodenal mucosal damage induced by nonsteroidal anti-inflammatory drugs. Dig Dis Sci. 1989;34:424–8.CrossRefPubMedGoogle Scholar
  33. 33.
    Yeomans ND, Naesdal J. Systematic review: ulcer definition in NSAID ulcer prevention trials. Aliment Pharmacol Ther. 2008;27:465–72.CrossRefPubMedGoogle Scholar
  34. 34.
    Suh D-C, Hunsche E, Shin H-C, Mavros P. Co-prescribing of proton pump inhibitors among chronic users of NSAIDs in the UK. Rheumatology. 2008;47:458–63.CrossRefPubMedGoogle Scholar
  35. 35.
    Arakawa T, Fujiwara Y, Sollano JD, Ahu Q, Kachintorn U, Rani AA, et al. IGIS study group: a questionnaire-based survey on the prescription of non-steroidal anti-inflammatory drugs by physicians in East Asian countries in 2007. Digestion. 2009;79:177–85.CrossRefPubMedGoogle Scholar
  36. 36.
    Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet. 2002;359:14–22.CrossRefPubMedGoogle Scholar
  37. 37.
    Coté GA, Rice JP, Bulsiewicz W, Norvell JP, Christensen K, Bobb A, et al. Use of physician education and computer alert to improve targeted use of gastroprotection among NSAID users. Am J Gastroenterol. 2008;103:1097–103.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2010

Authors and Affiliations

  • Hidetaka Tsumura
    • 1
  • Tsuyoshi Fujita
    • 1
  • Isamu Tamura
    • 1
  • Yoshinori Morita
    • 1
  • Masaru Yoshida
    • 1
  • Takashi Toyonaga
    • 1
  • Hidekazu Mukai
    • 2
  • Hideto Inokuchi
    • 3
  • Hiromu Kutsumi
    • 1
  • Takeshi Azuma
    • 1
  1. 1.Department of GastroenterologyKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of GastroenterologyYodogawa Christian HospitalOsakaJapan
  3. 3.Department of GastroenterologyHyogo Cancer CenterAkashiJapan

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