Guidelines for prevention of NSAID-related ulcer complications

American Journal of Gastroenterology

Volumn 104, Issue 3, 2009, Pages 728-738

  Lanza, Frank L ^a,b   Chan, Francis K L ^c   Quigley, Eamonn M M ^d   Inadomi, John ^e   Baroni, Darren ^e   Bernstein, David ^e   Brugge, William ^e   Chang, Lin ^e   Cunningham, John ^e   Dendrinos, Kleanthis G ^e   DeVault, Kenneth ^e   Edmundowicz, Steven ^e   Ginsburg, Philip M ^e   Hornbuckle, Kelvin ^e   Kefalas, Costas ^e   Koch, Timothy ^e   Lehrer, Jenifer ^e   Lembo, Anthony ^e   O'Brien, John ^e   Papp Sr , John ^e   Parkman, Henry ^e   Perumalsamy, Kumaravel S ^e   Prasad, Ganapathy A ^e   Roach, Albert ^e   Sampliner, Richard ^e   Sonnenberg, Amnon ^e   Vargo, John ^e   Vege, Santhi Swaroop ^e   Vela, Marcelo ^e   Zein, Nizar ^e   Zuckerman, Marc J ^e   more..

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b Houston Institute for Clinical Research   (United States)

^c CHINESE UNIVERSITY OF HONG KONG   (Hong Kong)

^d UNIVERSITY COLLEGE CORK   (Ireland)

^e NONE

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ANTICOAGULANT AGENT; BISMUTH; CELECOXIB; CORTICOSTEROID; DICLOFENAC; ESOMEPRAZOLE; ETODOLAC; ETORICOXIB; FAMOTIDINE; HISTAMINE H2 RECEPTOR ANTAGONIST; IBUPROFEN; INDOMETACIN; KETOROLAC; LANSOPRAZOLE; LUMIRACOXIB; MELOXICAM; MISOPROSTOL; NABUMETONE; NAPROXEN; NONSTEROID ANTIINFLAMMATORY AGENT; OMEPRAZOLE; PIROXICAM; PLACEBO; RANITIDINE; ROFECOXIB; SUCRALFATE; SULINDAC; UNINDEXED DRUG; VALDECOXIB;

ABDOMINAL CRAMP; CLINICAL PRACTICE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; DIARRHEA; DIGESTIVE SYSTEM PERFORATION; DRUG FATALITY; DRUG MEGADOSE; DUODENUM ULCER; EPIDERMOLYSIS; GASTRODUODENAL ULCER; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL OBSTRUCTION; HEART INFARCTION; HELICOBACTER INFECTION; HUMAN; MEDICAL RESEARCH; OSTEOARTHRITIS; PEPTIC ULCER BLEEDING; PLASMA HALF LIFE; PRACTICE GUIDELINE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; REVIEW; RHEUMATOID ARTHRITIS; RISK FACTOR; SIDE EFFECT; STOMACH ULCER; STROKE; SUDDEN DEATH;

ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTI-ULCER AGENTS; ANTICOAGULANTS; ASPIRIN; CYCLOOXYGENASE 2 INHIBITORS; HELICOBACTER INFECTIONS; HELICOBACTER PYLORI; HISTAMINE H2 ANTAGONISTS; HUMANS; MISOPROSTOL; PEPTIC ULCER; PEPTIC ULCER HEMORRHAGE; PROTON PUMP INHIBITORS; RISK FACTORS;

EID: 61949239030     PISSN: 00029270     EISSN: 15720241     Source Type: Journal    
DOI: 10.1038/ajg.2009.115     Document Type: Review

References (113)

1. Cryer B, Feldman M. Effects of nonsteroidal anti-inflammatory drugs on endogenous gastrointestinal prostaglandins and therapeutic strategies for prevention and treatment of nonsteroidal, anti-inflammatory drug-induced damage. Arch Intern Med 1992;152:1145-55.
2. Soll AH, Weinstein WM, Kurata J et al. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med 1991;114:307-19.
3. Larkai EN, Smith JL, Lidsky MD et al. Gastroduodenal mucosa and dyspeptic symptoms in arthritic patients during chronic nonsteroidal antiinflammatory drug use. Am J Gastroenterol 1987;82:1153-8.
4. Laine L. Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin North Am 1996;6:489-504.
5. 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. Celecoxib Long-term Arthritis Safety Study. JAMA 2000;284:1247-55.
6. Bombardier C, Laine L, Reicin A et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR study group. N Engl J Med 2000;343:1520-8.
7. Singh G. Gastrointestinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, Rheumatism, and Aging Medical Information System. Am J Ther 2000;7:115-21.
8. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol Suppl 1999;56:18-24.
9. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. N Engl J Med 1999;340:1888-99.
10. 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.
11. 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.
12. Fries JF, Williams CA, Bloch DA et al. Nonsteroidal anti-inflammatory drug- associated gastropathy: incidence and risk factor models. Am J Med 1991;91:213-22.
13. Dube C, Rostom A, Lewin G et al. The use of aspirin for primary prevention of colorectal cancer: a systematic review prepared for the US Preventive Services Task Force. Ann Intern Med 2007;146:365-75.
14. Rostom A, Dube C, Lewin G et al. Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the US Preventive Services Task Force. Ann Intern Med 2007;146:376-89.
15. Griffin MR, Ray WA, Schaffner W. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Intern Med 1988;109:359-63.
16. Griffin MR, Piper JM, Daugherty JR et al. Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med 1991;114:257-63.
17. Piper JM, Ray WA, Daugherty JR et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991;114:735-40.
18. Shorr RJ, Ray WA, Daugherty JR et al. Concurrent use of nonsteroidal antiinflammatory drugs and oral anticoagulants places elderly persons at high risk for hemorrhagic peptic ulcer disease. Arch Intern Med 1993;153:1665-70.
19. Allison MC, Howatson AG, Torrance CJ et al. Gastrointestinal damage associated with the use of nonsteroidal anti-inflammatory drugs. N Engl J Med 1992;327:749-54.
20. Carson JL, Strom BL, Morse ML et al. The relative gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs. Arch Intern Med 1987;147:1054-9.
21. Beardon PH, Brown SV, McDevitt DG. Gastrointestinal events in patients prescribed nonsteroidal anti-inflammatory drugs. A controlled study using record linkage in Tayside. Q J Med 1989;71:497-505.
22. Bloom BS. Risk and cost of gastrointestinal side effects associated with nonsteroidal anti-inflammatory drugs. Arch Intern Med 1989;149:1019-22.
23. 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;123:241-9.
24. Garcia Rodriguez LA, Hernandez-Diaz S. Relative risk of upper gastrointestinal complications among users of acetaminophen and nonsteroidal anti-inflammatory drugs. Epidemiology 2001;12:570-6.
25. Hernandez-Diaz S, Rodriguez LA. Association between nonsteroidal antiinflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med 2000;160:2093-9.
26. de Abajo FJ, Garcia Rodriguez LA. Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and entericcoated formulations. BMC Clin Pharmacol 2001;1:1.
27. Simon LS, Mills JA. Nonsteroidal anti-inflammatory drugs. N Engl J Med 1980;302:1179-85, 1237-43.
28. Lanas A, Perez-Aisa MA, Feu F et al. A nationwi de study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal anti-inflammatory drug use. Am J Gastroenterol 2005;100:1685-93.
29. Steering Committee of the Physicians Health Study Research Group. Final report on the aspirin component of the ongoing Physicians' Health Study. N Engl J Med 1989;321:129-35.
30. Slattery J, Warlow CP, Shorrock CJ et al. Risks of gastrointestinal bleeding during secondary prevention of vascular events with aspirin - analysis of gastrointestinal bleeding during the UK-TIA trial. Gut 1995;37:509-11.
31. Naschitz JE, Yeshurun B, Odeh M et al. Overt gastrointestinal bleeding in the course of chronic low dose aspirin administration for secondary prevention of arterial occlusive disease. Am J Gastroenterol 1990;85:408-11.
32. Kurata JH, Abbey DE. The effect of chronic aspirin use on duodenal and gastric ulcer hospitalizations. J Clin Gastroenterol 1990;12:260-6.
33. McQuaid KR, Laine L. Systemic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med 2006;119:624-38.
34. Serrano P, Lanas A, Arroyo MT et al. Risk of upper gastrointestinal bleeding in patients taking low-dose aspirin for the prevention of cardiovascular diseases. Aliment Pharmacol Ther 2002;16:1945-53.
35. Laine L. Review article: gastrointestinal bleeding with low-dose aspirin - what's the risk? Aliment Pharmacol Ther 2006;24:897-908.
36. Graham DY. Ulcer complications and their nonoperative treatment. In: Sleisenger MH, Fordtran JS (eds). Gastrointestinal Disease. Pathophysiology, Diagnosis and Management. 5th edn. WB Saunders Co: Philadelphia, 1993, pp. 698-712.
37. Graham DY, Lew GM, Klein PD et al. Effect of treatment of Helicobacter pylori infection on the long-term recurrence of gastric or duodenal ulcer. A randomized, controlled study. Ann Intern Med 1992;116:705-8.
38. Chan FK. Helicobacter pylori and non-steroidal anti-inflammatory drugs. Gastroenterol Clin North Am 2001;30:937-52.
39. Huang JQ, Sridhar S, Hunt RH. Role of Helicobacter pylori infection and nonsteroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet 2002;359:14-22.
40. Vergara M, Catalan M, Gisbert JP et al. Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users. Aliment Pharmacol Ther 2005;21:1411-8.
41. Malfertheiner P, the European Helicobacter pylori Study Group. Current concepts in the management of Helicobacter pylori infection - The Maastricht 2-2000 Consensus report. Aliment Pharmacol Ther 2002;16:167-80.
42. Bazzoli F, DeLuca L, Graham DY. Helicobacter pylori infection and the use of NSAIDs. Best Pract Res Clin Gastroenterol 2001;15:775-85.
43. Chan FK, To KF, Wu JC et al. Eradication of Helicobacter pylori and risk of peptic ulcers in patients starting long-term treatment with nonsteroidal anti-inflammatory drugs: a randomized trial. Lancet 2002;359:9-13.
44. Leontiadis GI, Sreedharan A, Dorward S et al. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding. Health Technol Assess 2007;11:1-164.
45. Graham DY, Lidsky MD, Cox AM et al. Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection. Gastroenterology 1991;100:1653-7.
46. Labenz J, Blum AL, Bolten WW et al. Primary prevention of diclofenac associated ulcers and dyspepsia by omeprazole or triple therapy in Helicobacter pylori positive patients; a randomized, double blind, placebo controlled trial. Gut 2002;51:329-35.
47. Lai KC, Lam SK, Chu KM et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 2002;346:2033-8.
48. Chan FK, Chung SC, Suen BY 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;344:967-73.
49. Hawkey CJ, Tulassay Z, Szczepanski L et al. Randomized controlled trial of Helicobacter pylori eradication in patients on nonsteroidal antiinflammatory drugs: HELP NSAIDs study. Helicobacter Eradication for Lesion Prevention. Lancet 1998;352:1016-21.
50. Rostom A, Dube C, Wells G et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002;4:CD002296.
51. Hudson N, Taha AS, Russell RI et al. Famotidine for healing and maintenance in non-steroidal anti-inflammatory drug-associated gastroduodenal ulceration. Gastroenterology 1997;112:1817-22.
52. Lai KC, Lam SK, Chu KM et al. Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 2002;346:2033-8.
53. Ehsanullah RS, Page MC, Tildesley G et al. Prevention of gastroduodenal damage induced by nonsteroidal anti-inflammatory drugs: controlled trial of ranitidine. BMJ 1988;297:1017-21.
54. Robinson MG, Griffin JW Jr, Bowers J et al. Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal anti-inflammatory drugs. Dig Dis Sci 1989;34:424-8.
55. Lanza FL, Peace K, Gustitus L et al. A blinded endoscopic comparative study of misoprostol vs. sucralfate and placebo in the prevention of aspirin-induced gastric and duodenal ulceration. Am J Gastroenterol 1988;83:143-6.
56. Agrawal NM, Roth S, Graham DY et al. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. a randomized, controlled trial. Ann Intern Med 1991;115:195-200.
57. McCarthy DM. Sucralfate. N Engl J Med 1991;325:1017-25.
58. Lanza FL, Royer GL Jr, Nelson RS. Endoscopic evaluation of the effects of aspirin, buffered aspirin and enteric-coated aspirin on the gastric and duodenal mucosa. A controlled study. N Engl J Med 1980;303:136-8.
59. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ 2000;321:1183-7.
60. Lanza FL, Fakouhi D, Rubin A 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.
61. Targownik LE, Metge CJ, Leung S et al. The relative efficacies of gastroprotective strategies in chronic users of nonsteroidal anti-inflammatory drugs. Gastroenterology 2008;134:937-44.
62. 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.
63. Aadland E, Fausa O, Vatn M et al. Protection by misoprostol against naproxen-induced gastric mucosal damage. Am J Med 1987;83:37-40.
64. Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicenter, double-blind placebo-controlled trial. Lancet 1988;2:1277-80.
65. Graham DY, White RH, Moreland LW et al. Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group. Ann Intern Med 1993;119:257-62.
66. Raskin JB, White RH, Jackson JE et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med 1995;123:344-50.
67. Bardhan KD, Bjarnason I, Scott DL et al. The prevention and healing of acute nonsteroidal anti-inflammatory drug-associated gastroduodenal mucosal damage by misoprostol. Br J Rheumatol 1993;32:990-5.
68. Elliott SL, Yeomans ND, Buchanan RR et al. EM cacy of 12 months ' misoprostol as prophylaxis against NSAID-induced gastric ulcers. A placebo-controlled trial. Scand J Rheumatol 1994;23:171-6.
69. R askin JB, White RH, J aszewski R et al. Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: a prospective, double-blind, multicenter study. Am J Gastroenterol 1996;91:223-7.
70. Koch M, Dezi A, Ferrario F et al. Prevention of nonsteroidal antiinflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials. Arch Intern Med 1996;156:2321-2.
71. Rostom A, Dube C, Wells G et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002;4:CD002296.
72. G raham 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;162:160-75.
73. Yeomans ND, Tulassay Z, Juhasz L et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal anti-inflammatory drugs. Acid Suppression Trial: Ranitidine vs. Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group. N Engl J Med 1998;338:719-26.
74. Hawkey CJ, Karrasch JA, Szczepanski L et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal anti-inflammatory drugs. Omeprazole vs. Misoprostol for NSAID-Induced Ulcer Management (OMNIUM) Study Group. N Engl J Med 1998;338:727-34.
75. Scheiman JM, Yeomans ND, Talley NJ 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.
76. Lanas A, Garcia-Rodriguez LA, Arroyo MT et al. EF ect of antisecretory drugs and nitrates on the risk of ulcer bleeding associated with nonsteroidal anti-inflammatory drugs, antiplatelet agents, and anticoagulants. Am J Gastroenterol 2007;102:507-15.
77. Regula J, Butruk E, Dekkers CP et al. Prevention of NSAID-associated gastrointestinal lesions: a comparison study pantoprazole vs. omeprazole. Am J Gastroenterol 2006;101:1747-55.
78. García Rodríguez LA, Ruigómez A. Secondary prevention of upper gastrointestinal bleeding associated with maintenance acid-suppressing treatment in patients with peptic ulcer bleed. Epidemiology 1999;10:228-32.
79. Laine L, Curtis SP, Cryer B, et al., MEDAL Steering Committee. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomized comparison. Lancet 2007;369:465-73.
80. Leontiadis GI, Sreedharan A, Dorwa rd S et al. Systematic reviews of the clinical effectiveness and cost-effectiveness of proton pump inhibitors in acute upper gastrointestinal bleeding. Health Technol Assess 2007;11:1-164.
81. B rown TJ, Hooper L, Elliott RA et al. A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal antiinflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modeling. Health Technol Assess 2006;10:iii-iv, xi-xiii, 1-183.
82. Elliott RA, Hooper L, Payne K et al. Preventing non-steroidal antiinflammatory drug-induced gastrointestinal toxicity: are older strategies more cost-effective in the general population? Rheumatology 2006;45:606-13.
83. Schoen RT, Vender RJ. Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Am J Med 1989;86:449-58.
84. Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem 1993;268:6610-4.
85. Hollander D. Gastrointestinal complications of nonsteroidal antiinflammatory drugs: prophylactic and therapeutic strategies. Am J Med 1994;96:274-81.
86. Scheiman JM. NSAIDs, gastrointestinal injury and cytoprotection. Gastroenterol Clin North Am 1996;25:279-98.
87. Cryer B. Nonsteroidal anti-inflammatory drugs and gastrointestinal disease. In: Feldman M, Scharschmidt BF, Sleisenger MH (eds). Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, and Management. 6th edn. Vol 1, W.B. Saunders: Philadelphia, 1998, pp. 343-57.
88. Laine L, Takeuchi K, Tarnawski A. Gastric mucosal defense and cytoprotection: bench to bedside. Gastroenterology 2008;135:41-60.
89. Bensen WG, Fiechtner JJ, McMillen JI et al. Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc 1999;74:1095-105.
90. Simon LS, Weaver AL, Graham DY et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 1999;282:1921-8.
91. Emery P, Zeidler H, Kvien TK et al. Celecoxib vs. diclofenac in long-term management of rheumatoid arthritis: randomized double-blind comparison. Lancet 1999;354:2106-11.
92. Laine L, Harper S, Simon T et al. A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Rofecoxib Osteoarthritis Endoscopy Study Group. Gastroenterology 1999;117:776-83.
93. Goldstein JL, Correa P, Zhao WW et al. Reduced incidence of gastroduodenal ulcers with celecoxib, a novel cyclooxygenase-2 inhibitor, compared to naproxen in patients with arthritis. Am J Gastroenterol 2001;96:1019-27.
94. Goldstein JL, Kivitz AJ, Verburg KM et al. A comparison of the upper gastrointestinal mucosa effects of valdecoxib, naproxen and placebo in healthy elderly subjects. Aliment Pharmacol Ther 2003;18:125-32.
95. Chan FK, Hung LCT, Suen BY et al. Celecoxib vs. diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology 2004;127:1038-43.
96. Chan FK, Wong VW, Suen BY 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 randomized trial. Lancet 2007;369:1621-6.
97. Laine L, Maller ES, Yu C et al. Ulcer formation with low-dose entericcoated aspirin and the effect of COX-2 selective inhibition: a double-blind trial. Gastroenterology 2004;127:395-402.
98. 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: randomized controlled trial. Lancet 2004;364:665-74.
99. Lanas A, Garcia-Rodriguez LA, Arroyo MT 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.
100. Garcia-Rodriguez LA, Barreales Tolosa L. Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population. Gastroenterology 2007;132:790-4.
101. Lanas A, Baron JA, Sandler RS et al. Peptic ulcer and bleeding events associated with rofecoxib in a 3-year colorectal adenoma chemoprevention trial. Gastroenterology 2007;132:490-7.
102. Laine L, Curtis SP, Cryer B et al. Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomized comparison. Lancet 2007;369:465-73.
103. Rostom A, Muir K, Dube C et al. Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane collaboration systematic review. Clin Gastroenterol Hepatol 2007;5:818-28. e5.
104. FDA Public Health Advisory. http://www.fda.gov/cder/drug/advisory/COX2. htm, April 7, 2005.
105. Farkouh ME, Greenberg JD, Jeger RV et al. Cardiovascular outcomes in high-risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Ann Rheum Dis 2007;66:764-70.
106. Bresalier RS, Sandler RS, Quan H et al. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005;352:1092-102.
107. Solomon SD, McMurray JJV, Pfeffer MA et al. Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005;352:1074-80.
108. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 2006;296:1633-44
109. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomized trials. BMJ 2006;332:1302-8.
110. Graham DY, Chan FK. NSAIDs, risks, and gastroprotective strategies: current status and future. Gastroenterology 2008;134:1240-6.
111. 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;93:2037-46.
112. Scheiman JM, Fendrick AM. Summing the risk of NSAID therapy. Lancet 2007;369:1580-1.
113. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1-8.