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Prevention and Treatment of NSAID Gastropathy

  • Stomach (C Howden, Section Editor)
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Opinion statement

Nonsteroidal anti-inflammatory drug (NSAID) treatment will be necessary as part of our therapeutic armamentarium for many years to come. Therefore, safe prescription is mandatory in order to prevent adverse events. In the last two decades, new strategies and new drugs have been developed to reduce NSAID-associated upper gastrointestinal (GI) adverse events. Although the implementation of guidelines into clinical practice takes time, several studies have shown a recent and profound decrease in hospitalizations due to upper GI complications, which has been linked to widespread use of proton pump inhibitors (PPIs), better NSAID prescription, and decreased prevalence of Helicobacter pylori infection. This is encouraging.

Safe NSAID prescription should be straightforward since the most relevant aspects are clinical in nature. Before issuing any prescription, three key questions should be considered:

1) Is NSAID treatment necessary for this patient?

2) What cardiovascular (CV) and GI risk factors does this patient have?

3) What is the most suitable NSAID for this patient?

GI and CV risk are easy to estimate, and we know that these risks are not the same for all NSAIDs. Selective cyclooxygenase (COX)-2 inhibitors, like celecoxib at usual doses, carry the lowest GI risk and are the best option in patients with moderate/high GI risk without high CV risk. Gastroprotective therapy (PPI as the drug of choice) should be considered if a non-selective NSAID is prescribed. For those at the highest risk, a combination of PPI plus a coxib is the best option. Also, eradication of H. pylori infection in patients with previous peptic ulcer or in NSAID-naïve users must be considered. Naproxen is the best option in patients with high CV risk and low/moderate GI risk.

Patients taking aspirin represent a real challenge for treatment, since interaction with frequently prescribed NSAIDs (e.g. ibuprofen/naproxen) may alter its antiplatelet effect, representing a potential clinical problem. Switching treatment (e.g. taking aspirin before NSAID dosing) may not be an alternative since interaction may persist, especially when taking enteric-coated aspirin. Changing NSAID treatment to diclofenac/celecoxib/etoricoxib may also not be an option in patients with high or previous CV event history. Under these circumstances, careful prescription should be considered at the individual patient level.

When dyspepsia develops in an NSAID user, PPI co-therapy plus reduction of the NSAID dose or a change in the type of NSAID are valid alternatives, but clinical experience shows that, for some patients, stopping NSAID therapy may be the only option. After a bleeding episode, most patients can be managed with alternative therapy to NSAIDs, but if needed, a coxib plus a PPI and H. pylori eradication is a safe alternative.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Lanza FL, Chan FK, Quigley EM, Practice Parameters Committee of the American College of Gastroenterology. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol. 2009;104(3):728–38.

    Article  PubMed  Google Scholar 

  2. Lee C, Straus WL, Balshaw R, Barlas S, Vogel S, Schnitzer TJ. A comparison of the efficacy and safety of nonsteroidal antiinflammatory agents versus acetaminophen in the treatment of osteoarthritis: a meta-analysis. Arthritis Rheum. 2004;51(5):746–54.

    Article  PubMed  CAS  Google Scholar 

  3. 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 

  4. Laine L. GI risk and risk factors of NSAIDs. J Cardiovasc Pharmacol. 2006;47 Suppl 1:S60–6.

    Article  PubMed  CAS  Google Scholar 

  5. Dubois RW, Melmed GY, Henning JM, Laine L. 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(2):197–208.

    Article  PubMed  CAS  Google Scholar 

  6. 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(10):787–96.

    Article  PubMed  CAS  Google Scholar 

  7. 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(9300):14–22.

    Article  PubMed  CAS  Google Scholar 

  8. Vergara M, Catalán M, Gisbert JP, Calvet X. Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users. Aliment Pharmacol Ther. 2005;21(12):1411–8.

    Article  PubMed  CAS  Google Scholar 

  9. Tang CL, Ye F, Liu W, Pan XL, Qian J, Zhang GX. Eradication of Helicobacter pylori infection reduces the incidence of peptic ulcer disease in patients using nonsteroidal anti-inflammatory drugs: a meta-analysis. Helicobacter. 2012;17(4):286–96.

    Article  PubMed  CAS  Google Scholar 

  10. Chan FK, Chung SC, Suen BY, Lee YT, Leung WK, Leung VK, et al. Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med. 2001;344(13):967–73.

    Article  PubMed  CAS  Google Scholar 

  11. Chan FK, To KF, Wu JC, Yung MY, Leung WK, Kwok T, et al. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with non-steroidal anti-inflammatory drugs: a randomised trial. Lancet. 2002;359:9–13.

    Article  PubMed  CAS  Google Scholar 

  12. American Gastroenterological Association, Wilcox CM, Allison J, Benzuly K, Borum M, Cryer B, et al. Consensus development conference on the use of nonsteroidal anti-inflammatory agents, including cyclooxygenase-2 enzyme inhibitors and aspirin. Clin Gastroenterol Hepatol. 2006;4(9):1082–9.

    Article  PubMed  CAS  Google Scholar 

  13. Lanas A, Benito P, Alonso J, Hernández-Cruz B, Barón-Esquivias G, Perez-Aísa Á, et al. Safe prescription recommendations for non steroidal anti-inflammatory drugs: consensus document ellaborated by nominated experts of three scientific associations (SER-SEC-AEG). Gastroenterol Hepatol. 2014;37(3):107–27. This Spanish consensus between three scientific societies (Gastro, Reuma, and Cardio) provides recommendations for the appropriate prescription of NSAID based on current scientific evidence, and according to gastrointestinal and cardiovascular patient’s risk.

    Article  PubMed  Google Scholar 

  14. Rostom A, Muir K, Dube C, Lanas A, Jolicoeur E, Tugwell P. Prevention of NSAID-related upper gastrointestinal toxicity: a meta-analysis of unsaid with gastroprotection and COX-2 inhibitors. Drug Health Patient Saf. 2009;1:1–25.

    Google Scholar 

  15. Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA, et al. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation. 2007;115(12):1634–42.

    Article  PubMed  Google Scholar 

  16. Capone ML, Sciulli MG, Tacconelli S, Grana M, Ricciotti E, Renda G, et al. Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol. 2005;45(8):1295–301.

    Article  PubMed  CAS  Google Scholar 

  17. Catella-Lawson F, Reilly MP, Kapoor SC, Cucchiara AJ, DeMarco S, Tournier B, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345(25):1809–17.

    Article  PubMed  CAS  Google Scholar 

  18. Johnsen SP, Sørensen HT, Mellemkjoer L, Blot WJ, Nielsen GL, McLaughlin JK, et al. Hospitalisation for upper gastrointestinal bleeding associated with use of oral anticoagulants. Thromb Haemost. 2001;86(2):563–8.

    PubMed  CAS  Google Scholar 

  19. Knijff-Dutmer EA, Schut GA, van de Laar MA. Concomitant coumarin-NSAID therapy and risk for bleeding. Ann Pharmacother. 2003;37(1):12–6.

    Article  PubMed  CAS  Google Scholar 

  20. Shorr RI, Ray WA, Daugherty JR, Griffin MR. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med. 1993;153(14):1665–70.

    Article  PubMed  CAS  Google Scholar 

  21. 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(1):27–31.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Karim A, Tolbert D, Piergies A, Hubbard RC, Harper K, Wallemark CB, et al. Celecoxib does not significantly alter the pharmacokinetics or hypoprothrombinemic effect of warfarin in healthy subjects. J Clin Pharmacol. 2000;40(6):655–63.

    Article  PubMed  CAS  Google Scholar 

  23. Van Hecken A, Schwartz JI, Depré M, De Lepeleire I, Dallob A, Tanaka W, et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. J Clin Pharmacol. 2000;40(10):1109–20.

    PubMed  Google Scholar 

  24. Cheetham TC, Levy G, Niu F, Bixler F. Gastrointestinal safety of nonsteroidal antiinflammatory drugs and selective cyclooxygenase-2 inhibitors in patients on warfarin. Ann Pharmacother. 2009;43(11):1765–73.

    Article  PubMed  CAS  Google Scholar 

  25. Dentali F, Douketis JD, Woods K, Thabane L, Foster G, Holbrook A, et al. Does celecoxib potentiate the anticoagulant effect of warfarin? A randomized, double-blind, controlled trial. Ann Pharmacother. 2006;40(7-8):1241–7.

    Article  PubMed  CAS  Google Scholar 

  26. Garcia Rodríguez LA, Hernández-Díaz S. The risk of upper gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs, glucocorticoids, acetaminophen, and combinations of these agents. Arthritis Res. 2001;3(2):98–101.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther. 2008;27(1):31–40.

    Article  PubMed  CAS  Google Scholar 

  28. Coxib and traditional NSAID Trialists’ (CNT) Collaboration, Bhala N, Emberson J, Merhi A, Abramson S, Arber N, et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382(9894):769–79. Meta-analysis of 754 NSAID trials based individual patients’ data, which evaluates both vascular, upper GI serious events. It shows clearly that naproxen is neutral in terms of CV risk whereas carries the highest GI risk. Coxibs and other non-selective NSAIDS (Ibuprofen and diclofenac) have similar CV risk. Coxibs have the lower GI risk.

    Article  PubMed  CAS  Google Scholar 

  29. Crooks CJ, West J, Card TR. Comorbidities affect risk of nonvariceal upper gastrointestinal bleeding. Gastroenterology. 2013;144(7):1384–93.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lanas A, Tornero J, Zamorano JL. Assessment of gastrointestinal and cardiovascular risk in patients with osteoarthritis who require NSAIDs: the LOGICA study. Ann Rheum Dis. 2010;69(8):1453–8. This study evaluates both GI and CV risks of NSAID users in the general population, suffering from osteoarthritis. The majority of patients have increased GI and CV risk; 15.5 % of patients presented a very high-risk profile, having high GI and CV risks.

    Article  PubMed  Google Scholar 

  31. Lanas A, García-Rodríguez LA, Arroyo MT, Gomollón F, Feu F, González-Pérez A, et al. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut. 2006;55:1731–8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Castellsague J, Riera-Guardia N, Calingaert B, Varas-Lorenzo C, Fourrier-Reglat A, Nicotra F, et al. Individual NSAIDs and upper gastrointestinal complications: a systematic review and meta-analysis of observational studies (the SOS project). Drug Saf. 2012;35(12):1127–46. Meta-analysis of observational studies that evaluate individual GI risk of the different type of NSAIDs. They confirmed the variability in the risk of upper GI complications among individual NSAIDs as used in clinical practice. Aceclofenac, celecoxib, and low-dose ibuprofen show the lowest GI risk. They confirm serious limitations of the study concerning validation of complications and the scarce data on the effect of dose and duration of use of NSAIDs and on concurrent use of other medications.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  33. Massó González EL, Patrignani P, Tacconelli S, García Rodríguez LA. Variability among nonsteroidal antiinflammatory drugs in risk of upper gastrointestinal bleeding. Arthritis Rheum. 2010;62(6):1592–601. doi:10.1002/art.27412.

    Article  PubMed  Google Scholar 

  34. Jarupongprapa S, Ussavasodhi P, Katchamart W. Comparison of gastrointestinal adverse effects between cyclooxygenase-2 inhibitors and non-selective, non-steroidal anti-inflammatory drugs plus proton pump inhibitors: a systematic review and meta-analysis. J Gastroenterol. 2012;48(7):830–8.

    Article  PubMed  Google Scholar 

  35. Lanas A. Role of nitric oxide in the gastrointestinal tract. Arthritis Res Ther. 2008;10 Suppl 2:S4.

    Article  PubMed  PubMed Central  Google Scholar 

  36. 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.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Ng FH, Tunggal P, Chu WM, Lam KF, Li A, Chan K, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107(3):389–96.

    Article  PubMed  CAS  Google Scholar 

  38. Yeomans ND, Tulassay Z, Juhász L, Rácz I, Howard JM, van Rensburg CJ, 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. Engl. J Med. 1998;338(11):719–26.

    CAS  Google Scholar 

  39. Koch M, Dezi A, Ferrario F, Capurso I. Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials. Arch Intern Med. 1996;156(20):2321–32.

    Article  PubMed  CAS  Google Scholar 

  40. 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.

    PubMed  Google Scholar 

  41. Graham DY, Agrawal NM, Campbell DR, Haber MM, Collis C, Lukasik NL, et al. NSAID-Associated Gastric Ulcer Prevention Study Group. 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 

  42. Ramiro S, Radner H, van der Heijde DM, Buchbinder R, Aletaha D, Landewé RB. Combination therapy for pain management in inflammatory arthritis: a Cochrane systematic review. J Rheumatol Suppl. 2012;90:47–55.

    Article  PubMed  CAS  Google Scholar 

  43. Chan TY. Adverse interactions between warfarin and nonsteroidal antiinflammatory drugs: mechanisms, clinical significance, and avoidance. Ann Pharmacother. 1995;29(12):1274–83.

    PubMed  CAS  Google Scholar 

  44. Laine L, Bombardier C, Hawkey CJ, Davis B, Shapiro D, Brett C, 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 

  45. Ament PW, Dicola DB, James ME. Reducing adverse effects of proton pump inhibitors. Am Fam Physician. 2012;86(1):66–70.

    PubMed  Google Scholar 

  46. Ho PM, Maddox TM, Wang L, Fihn SD, Jesse RL, Peterson ED, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA. 2009;301:937–44.

    Article  PubMed  CAS  Google Scholar 

  47. Juurlink DN, Gomes T, Ko DT, Szmitko PE, Austin PC, Tu JV, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180:713–8.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Siller-Matula JM, Jilma B, Schrör K, Christ G, Huber K. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis. J Thromb Haemost. 2010;8(12):2624–41.

    Article  PubMed  CAS  Google Scholar 

  49. Kwok CS, Nijjar RS, Loke YK. Effects of proton pump inhibitors on adverse gastrointestinal events in patients receiving clopidogrel: systematic review and meta-analysis. Drug Saf. 2011;34(1):47–57.

    Article  PubMed  CAS  Google Scholar 

  50. Gerson LB, McMahon D, Olkin I, Stave C, Rockson SG. Lack of significant interactions between clopidogrel and proton pump inhibitor therapy: meta-analysis of existing literature. Dig Dis Sci. 2012;57(5):1304–13.

    Article  PubMed  CAS  Google Scholar 

  51. Kwok CS, Jeevanantham V, Dawn B, Loke YK. No consistent evidence of differential cardiovascular risk amongst proton-pump inhibitors when used with clopidogrel: meta-analysis. Int J Cardiol. 2013;167(3):965–74. This recent meta-analysis evaluated the possible interaction of clopidogrel and PPI. The clinical validity or relevance of the hypothesized PPI-clopidogrel interaction remains questionable.

    Article  PubMed  Google Scholar 

  52. Chan FK, Wong VW, Suen BY, Wu JC, Ching JY, Hung LC, et al. Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial. Lancet. 2007;369(9573):1621–6.

    Article  PubMed  CAS  Google Scholar 

  53. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011;8(9):e1001098. doi:10.1371/journal.pmed.1001098. Important and relevant systematic review and meta-analysis that provides the relative CV risk of various NSAIDs and coxibs at typical doses in a community setting.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  54. Lanas A, Garcia-Tell G, Armada B, Oteo-Alvaro A. Prescription patterns and appropriateness of NSAID therapy according to gastrointestinal risk and cardiovascular history in patients with diagnoses of osteoarthritis. BMC Med. 2011;9:38.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Jones R. Nonsteroidal anti-inflammatory drug prescribing: past, present, and future. Am J Med. 2001;110:4S–7S.

    Article  PubMed  CAS  Google Scholar 

  56. Lanas A, Hirschowitz BI. Toxicity of NSAIDs in the stomach and duodenum. Eur J Gastroenterol Hepatol. 1999;11:375–81.

    Article  PubMed  CAS  Google Scholar 

  57. Laine L. Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin N Am. 1996;6:489–504.

    PubMed  CAS  Google Scholar 

  58. Silverstein FE, Graham DY, Senior JR, Davies HW, Struthers BJ, Bittman RM, 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;123:241–9.

    Article  PubMed  CAS  Google Scholar 

  59. Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med. 1995;105:31S–8S.

    Article  Google Scholar 

  60. Lanas A, Perez-Aisa MA, Feu F, Ponce J, Saperas E, Santolaria S, 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;100:1685–93.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  62. Larkai EN, Smith JL, Lidsky MD, Graham DY. Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic steroidal anti-inflammatory drug use. Am J Gastroenterol. 1987;82:1153–8.

    PubMed  CAS  Google Scholar 

  63. Yeomans ND, Lanas A, Talley NJ, Thomson AB, Daneshjoo R, Eriksson B, et al. Prevalence and incidence of gastroduodenal ulcers during treatment with vascular protective doses of aspirin. Aliment Pharmacol Ther. 2005;22(9):795–801.

    Article  PubMed  CAS  Google Scholar 

  64. Hawkey C, Talley NJ, Yeomans ND, Jones R, Sung JJ, Lamstrong 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.

    Article  PubMed  CAS  Google Scholar 

  65. Niculescu L, Li C, Huang J, Mallen S. Pooled analysis of GI tolerability of 21 randomized controlled trials of celecoxib and nonselective NSAIDs. Curr Med Res Opin. 2009;25(3):729–40. doi:10.1185/03007990802714382.

    Article  PubMed  CAS  Google Scholar 

  66. Cryer BL, Sostek MB, Fort JG, Svensson O, Hwang C, Hochberg MC. A fixed-dose combination of naproxen and esomeprazole magnesium has comparable upper gastrointestinal tolerability to celecoxib in patients with osteoarthritis of the knee: results from two randomized, parallel-group, placebo-controlled trials. Ann Med. 2011;43(8):594–605. Two 12-week RCTs comparing two gastropreventive strategies: PPI plus traditional NSAIDs versus COX-2 selective inhibitors. Naproxen/esomeprazole magnesium has upper GI tolerability comparable to that of celecoxib in patients with osteoarthritis.

    Article  PubMed  CAS  Google Scholar 

  67. Lai K, Hui W, Wong B, Hu W, Chan O, Lam S. Lansoprazole but not rofecoxib reduced dyspeptic symptoms of patients on NSAIDs. Gastroenterology. 2005;128 Suppl 2:A137.

    Google Scholar 

  68. Tannenbaum H, Bombardier C, Davis P, Russell AS. Third Canadian Consensus Conference Group. An evidence based approach to prescribing nonsteroidal antiinflammatory drugs. Third Canadian Consensus Conference. J Rheumatol. 2006;33:140–57. Erratum in: J Rheumatol. 2006;33:829 and J Rheumatol. 2006;33:440.

    PubMed  Google Scholar 

  69. Holster IL, Kuipers EJ. Management of acute nonvariceal upper gastrointestinal bleeding: current policies and future perspectives. World J Gastroenterol. 2012;18(11):1202–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  70. Ramsoekh D, Van Leerdam ME, Rauws EAJ, Tygat GN. Outcome of peptic ulcer bleeding, nonsteroidal anti-inflammatory drug use and Helicobacter pylori infection. Clin Gastroenterol Hepatol. 2005;3:859–64.

    Article  PubMed  Google Scholar 

  71. Rockall T, Logan R, Devlin H, Northfield T. Incidence and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. BMJ. 1995;311:222–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  72. Barkun A, Sabbah S, Enns R, Amstrong D, Fedorak RN, Rahme E, et al. The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): endoscopic hemostasis and proton pump inhibition are associated with improved outcomes in a real-life setting. Am J Gastroenterol. 2004;99:1238–46.

    Article  PubMed  Google Scholar 

  73. Marmo R, Koch M, Cipoletta L, Capurso L, Pera A, Bianco MA, et al. Predictive factors of mortality from nonvariceal upper gastrointestinal hemorrhage: a multicenter study. Am J Gastroenterol. 2008;103:1639–47.

    Article  PubMed  Google Scholar 

  74. Laine L, Yang H, Chang SC, Datto C. Trends for incidence of hospitalization and death due to GI complications in the United States from 2001–2009. Am J Gastroenterol. 2012;107:1190–5.

    Article  PubMed  Google Scholar 

  75. Lanas A, Aabakken L, Fonseca J, Mungan ZA, Papatheodoridis GV, Piessevaux H, et al. Clinical predictors of poor outcomes among patients with nonvariceal upper gastrointestinal bleeding in Europe. Aliment Pharmacol Ther. 2011;33(11):1225–33.

    Article  PubMed  CAS  Google Scholar 

  76. Lancaster Smith MJ, Jadeberg ME, Jackson DA. Ranitidine in the treatment of non steroidal antiinflammtory drug associated gastric and duodenal ulcer. Gut. 1991;32:252–5.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  77. Walan A, Bader JP, Classen M, Lamers CB, Piper DW, Rutgersson K, et al. Effect of omeprazole and ranitidine on ulcer healing and relaspe rates in patients with benign gastric ulcer. N Engl J Med. 1989;320:69–75.

    Article  PubMed  CAS  Google Scholar 

  78. Agrawal NM, Campbell DR, Safdi MA, Lukasik NL, Huang B, Haber MM. Superiority of lansoprazole vs ranitidine in healing nonsteroidal antiinflammatory drug-associated gastric ulcers: results of a double-blind, randomized, multicenter study. NSAID-Associated Gastric Ulcer Study Group. Arch Intern Med. 2000;160:1455–61.

    Article  PubMed  CAS  Google Scholar 

  79. Hawkey CJ, Karrasch JA, Szczepanski L, Walker DG, Barkun A, Swannell AJ, 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;338:727–34.

    Article  PubMed  CAS  Google Scholar 

  80. 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;101:701–10. PMID: 16494585.

    Article  PubMed  CAS  Google Scholar 

  81. Chan FK, Hung LC, Suen BY, Wu JC, Lee KC, Leung VK, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002;347:2104–10.

    Article  PubMed  CAS  Google Scholar 

  82. Lai KC, Chu KM, Hui WM, Wong BC, Hu WH, Wong WM, et al. Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. Am J Med. 2005;118:1271–8. PMID: 16271912.

    Article  PubMed  CAS  Google Scholar 

  83. 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. PMID: 18294634.

    Article  PubMed  CAS  Google Scholar 

  84. Rahme E, Barkun AN, Toubouti Y, Scalera A, Rochon S, Lelorier J. Do proton-pump inhibitors confer additional gastrointestinal protection in patients given celecoxib? Arthritis Rheum. 2007;57:748–55. PMID: 17530673.

    Article  PubMed  CAS  Google Scholar 

  85. Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, et al. International Consensus Upper Gastrointestinal Bleeding Conference Group International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152(2):101–13. A multidisciplinary group developed international guidelines to help clinicians make informed decisions regarding the management of patients who present with nonvariceal upper GI bleeding, which reflect the 2009 state of the art.

    Article  PubMed  Google Scholar 

  86. Jairath V, Hearnshaw S, Brunskill SJ, Doree C, Hopewell S, Hyde C, et al. Red cell transfusion for the management of upper gastrointestinal haemorrhage. Cochrane Database Syst Rev 2010; CD006613. doi:10.1002/14651858.CD006613.pub3.

  87. Villanueva C, Colomo A, Bosch A, Concepción M, Hernandez-Gea V, Aracil C, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013 Jan 3;368(1):11-21. doi: 10.1056/NEJMoa1211801. Erratum in: N Engl J Med. 2013 Jun 13;368(24):2341. This study compares restrictive and liberal transfusion strategies in acute upper GI bleeding events.

  88. Calvet X, Vergara M, Brullet E, Gisbert JP, Campo R. Addition of a second endoscopic treatment following epinephrine injection improves outcome in high risk bleeding ulcers. Gastroenterology. 2004;126:441–50.

    Article  PubMed  Google Scholar 

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Conflict of Interest

Carlos Sostres and Carla J. Gargallo report no conflict of interest.

Angel Lanas is a consultant for, or has received research grants from, AstraZeneca, Pfizer, and Bayer.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Service of Digestive Diseases, University Hospital Lozano Blesa, c/Domingo Miral s/n, 50009, Zaragoza, Spain

    Carla J. Gargallo MD, Carlos Sostres MD & Angel Lanas MD, DSc

  2. Aragon Health Sciences Institute, (IIS Aragón), Zaragoza, Spain

    Carla J. Gargallo MD, Carlos Sostres MD & Angel Lanas MD, DSc

  3. CIBERehd, Barcelona, Spain

    Angel Lanas MD, DSc

  4. University of Zaragoza, Zaragoza, Spain

    Angel Lanas MD, DSc

Authors
  1. Carla J. Gargallo MD
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  2. Carlos Sostres MD
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  3. Angel Lanas MD, DSc
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Correspondence to Angel Lanas MD, DSc.

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Gargallo, C.J., Sostres, C. & Lanas, A. Prevention and Treatment of NSAID Gastropathy. Curr Treat Options Gastro 12, 398–413 (2014). https://doi.org/10.1007/s11938-014-0029-4

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