Clinical Drug Investigation

, Volume 25, Issue 4, pp 265–270 | Cite as

Inadequate Use of Preventive Strategies in Patients Receiving NSAIDs

  • I. Francetic
  • M. Bilusic
  • V. Macolic-Sarinic
  • M. Huic
  • I. Mercep
  • K. Makar-Ausperger
  • V. Erdeljic
  • S. Mimica
  • I. Baotic
  • P. Simic
Original Research Article


Objective: Little is known about the factors that influence the decision to use NSAIDs in combination with gastroprotective drugs. The aims of this observational study were to evaluate the extent to which NSAID users are prescribed concomitant gastroprotective drug regimens (‘preventive strategies’), and to determine how patient risk factors for NSAID-associated gastrointestinal toxicity and physician prescribing preferences influenced the decision to prescribe a gastroprotective drug in combination with an NSAID.

Design and patients: The study was conducted on 29 June 2004 and comprised 109 eligible adult patients hospitalised at the Clinical Hospital Center, Zagreb. Use of NSAIDs and gastroprotective drugs, risk factors for NSAID-associated gastrointestinal toxicity, and physician prescribing preferences were monitored throughout the study.

Results: Sixty-six percent of patients receiving proton pump inhibitors or histamine H2-receptor antagonists with NSAIDs had no risk factors for gastrointestinal toxicity. Furthermore, 29% of patients who used NSAIDs had risk factors for gastrointestinal toxicity but were not receiving gastroprotective drugs. Even though patients at risk of NSAID-associated gastrointestinal complications had higher odds of receiving preventive strategies (odds ratio 1.25), the absolute rate of utilisation of these therapies in at-risk populations was unacceptably low (69%). However, the strongest independent correlation for gastroprotective drug use was the prescribing physician, with an odds ratio of 6.40.

Conclusion: This study demonstrates that an individual physician’s prescribing style largely determines the odds of receiving preventive strategies with NSAID treatment and is more important than the patient’s risk factors for gastrointestinal toxicity.


Omeprazole Proton Pump Inhibitor Misoprostol Gastrointestinal Toxicity Nsaid User 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This study received no external funding, and the authors have no potential conflicts of interest that are directly relevant to the contents of this manuscript.


  1. 1.
    Paakkari H. Epidemiological and financial aspects of the use of non-steroidal anti-inflammatory analgesics. Pharmacol Toxicol 1994; 75Suppl. 2: 56–9PubMedCrossRefGoogle Scholar
  2. 2.
    Giercksky KE, Huseby G, Rugstad HE. Epidemiology of NSAID-related gastrointestinal side effects. Scand J Gastroenterol Suppl 1989; 163: 3–8PubMedCrossRefGoogle Scholar
  3. 3.
    Topol EJ, Falk GW. A coxib a day won’t keep the doctor away. Lancet 2004; 364: 639–40PubMedCrossRefGoogle Scholar
  4. 4.
    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: 665–74PubMedCrossRefGoogle Scholar
  5. 5.
    Tacconelli S, Capone ML, Patrignani P. Clinical pharmacology of novel selective COX-2 inhibitors. Curr Pharm Des 2004; 10: 589–601PubMedCrossRefGoogle Scholar
  6. 6.
    Farkouh ME, Kirshner H, Harrington RA, et al. Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet 2004; 364: 675–84PubMedCrossRefGoogle Scholar
  7. 7.
    Graham DJ, Campen D, Hui R, et al. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 2005; 365: 475–81PubMedGoogle Scholar
  8. 8.
    Ivey KJ. Mechanisms of nonsteroidal anti-inflammatory drag-induced gastric damage: actions of therapeutic agents. Am J Med 1988; 84Suppl. 2A: 41–8PubMedCrossRefGoogle Scholar
  9. 9.
    Elliott SL, Ferris RJ, Giraud AS, et al. Indomethacin damage to rat gastric mucosa is markedly dependent on luminal pH. Clin Exp Pharmacol Physiol 1996; 23: 432–4PubMedCrossRefGoogle Scholar
  10. 10.
    Fries JF, Williams CA, Bloch DA, et al. Nonsteroidal antiinflammatory drug-associated gastropathy: incidence and risk factor models. Am J Med 1991; 91: 213–22PubMedCrossRefGoogle Scholar
  11. 11.
    Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med 1999; 340: 1888–99PubMedCrossRefGoogle Scholar
  12. 12.
    Laine L. Approaches to nonsteroidal anti-inflammatory drug use in the high risk patient. Gastroenterology 2001; 120: 594–606PubMedCrossRefGoogle Scholar
  13. 13.
    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: 2037–46PubMedCrossRefGoogle Scholar
  14. 14.
    Schoenfeld P, Kimmey MB, Scheiman J, et al. Review article: nonsteroidal anti-inflammatory drug-associated gastrointestinal complications — guidelines for prevention and treatment. Aliment Pharmacol Ther 1999; 13: 1273–85PubMedCrossRefGoogle Scholar
  15. 15.
    Lancaster-Smith MJ, Jaderberg ME, Jackson DA. Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers. Gut 1991; 32: 252–5PubMedCrossRefGoogle Scholar
  16. 16.
    Ehsanullah RS, Page MC, Tildesley G, et al. Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. BMJ 1988; 297: 1017–21PubMedCrossRefGoogle Scholar
  17. 17.
    Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet 1988; 2: 1277–80PubMedCrossRefGoogle Scholar
  18. 18.
    Walan A, Bader J-P, Classen M, et al. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med 1989; 320: 69–75PubMedCrossRefGoogle Scholar
  19. 19.
    Yeomans ND, Tulassay Z, Juhasz L, et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med 1998; 338: 719–26PubMedCrossRefGoogle Scholar
  20. 20.
    Hawkey CJ, Karrasch JA, Szczepanski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group. N Engl J Med 1998; 338: 727–34PubMedCrossRefGoogle Scholar
  21. 21.
    Solomon DH, Schneeweiss S, Glynn RJ, et al. Determinants of selective cyclooxygenase-2 inhibitor prescribing: are patient or physician characteristics more important? Am J Med 2003; 115: 715–20PubMedCrossRefGoogle Scholar
  22. 22.
    Parente F, Cucino C, Gallus S, et al. Hospital use of acid-suppressive medications and its fall-out on prescribing in general practice: a 1-month survey. Aliment Pharmacol Ther 2003; 17: 1503–6PubMedCrossRefGoogle Scholar
  23. 23.
    Sturkenboom MCJM, Burke TA, Dieleman JP, et al. Underutilization of preventive strategies in patients receiving NSAIDs. Rheumatology 2003; 42Suppl. 3: 23–31Google Scholar
  24. 24.
    Carvajal A, Arias LHM, Vega E. Gastroprotection during the administration of non-steroidal anti-inflammatory drags: a drug utilization study. Eur J Clin Pharmacol 2004; 60: 439–44PubMedCrossRefGoogle Scholar
  25. 25.
    Clinard F, Bardou M, Sgro C, et al. Non-steroidal anti-inflammatory and cytoprotective drag co-prescription in general practice. Eur J Clin Pharmacol 2001; 57: 737–43PubMedCrossRefGoogle Scholar
  26. 26.
    Chan FKL, Sung JY, Chung SCS, et al. Randomized trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet 1997; 350: 975–9PubMedCrossRefGoogle Scholar
  27. 27.
    Konturek JW, Fuchs W, Elbert J, et al. The prevalence of Helicobacter pylori infection in long-term users of nonsteroidal antiinflammatory drugs [abstract]. Gastroenterology 1998; 114: G0762CrossRefGoogle Scholar
  28. 28.
    Hawkey CJ, Tullassay Z, Szcepanski L, et al. Failure of Helicobacter pylori eradication to influence site-specific relapse in high risk NSAID users: results of a large six month double blind randomised controlled clinical trial [abstract]. Gastroenterology 1998; 114: G0594Google Scholar
  29. 29.
    Henry D, Lim L, Garcia Rodriguez L, et al. Variability in risk of gastrointestinal complications with individual NSAIDs: results of a collaborative meta-analysis. BMJ 1996; 312: 1563–6PubMedCrossRefGoogle Scholar
  30. 30.
    Rostom A, Dube C, Wells G, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002; 4: CD002296PubMedGoogle Scholar

Copyright information

© Adis Data Information BV 2005

Authors and Affiliations

  • I. Francetic
    • 1
  • M. Bilusic
    • 1
  • V. Macolic-Sarinic
    • 1
  • M. Huic
    • 1
  • I. Mercep
    • 1
  • K. Makar-Ausperger
    • 1
  • V. Erdeljic
    • 1
  • S. Mimica
    • 2
  • I. Baotic
    • 3
  • P. Simic
    • 1
  1. 1.Department of MedicineClinical Hospital RebroZagrebCroatia
  2. 2.Department of MedicineClinical Hospital RijekaRijekaCroatia
  3. 3.Department of MedicineGeneral Hospital ‘Vuk Vrhovac’ZagrebCroatia

Personalised recommendations