, Volume 72, Issue 12, pp 1605–1616 | Cite as

Therapeutic Management of Recurrent Peptic Ulcer Disease

Therapy In Practice


The epidemiology of peptic ulcer disease (PUD) has undergone significant changes since the discovery of Helicobacter pylori. Various aetiologies contribute to recurrent PUD. Ulcers related to untreated H. pylori infection tend to recur. Use of NSAIDs, low-dose aspirin and dual anti-platelet therapy have become important risk factors for recurrent ulcers and their complications as the proportion of H. pylori-related ulcers declines. Recent data have shown that H. pylori-negative, NSAID-negative idiopathic peptic ulcers are on the rise and carry a higher risk of recurrent ulcer bleeding and mortality. Effective management of recurrent PUD relies on identification and modification of treatable risk factors. Persistent H. pylori infection should be carefully ruled out. Choice of an effective H. pylori eradication regimen should be based on local antibacterial resistance patterns. For patients who need long-term NSAID therapy, the initial choice of an NSAID relates to a patient’s cardiovascular risk, and the need for therapy to decrease gastrointestinal (GI) complications is determined by the severity and number of GI risk factors. For patients on dual anti-platelet therapy, strategies to prevent recurrent ulcer disease and its complications centre on balancing the bleeding and thrombotic risks of individual patients. Long-term proton pump inhibitor maintenance therapy may be necessary to prevent recurrent ulcer bleeding for patients with ulcer bleeding from H. pylori-negative, NSAID-negative ulcers, and for patients who require NSAID or aspirin maintenance therapy.


  1. 1.
    Bardhan KD, Cole DS, Hawkins BW, et al. Does treatment with cimetidine extended beyond initial healing of duodenal ulcer reduce the subsequent relapse rate?. Br Med J 1982; 284 (6316): 621–3CrossRefGoogle Scholar
  2. 2.
    Gudmand-Hoyer F, Jensen KB, Krag E, et al. Prophylactic effect of cimetidine in duodenal ulcer disease. Br Med J 1978; 1 (6120): 1095–7PubMedCrossRefGoogle Scholar
  3. 3.
    Boyd EJ, Wilson JA, Wormsley KG. The fate of asympto-matic recurrences of duodenal ulcer. Scand J Gastroenterol 1984; 19: 808–12PubMedGoogle Scholar
  4. 4.
    Wolosin JD, Gertler SL, Peterson WL, et al. Gastric ulcer recurrence: follow-up of a double-blind, placebo-controlled trial. J Clin Gastroenterol 1989; 11: 12–6PubMedCrossRefGoogle Scholar
  5. 5.
    Marshall BJ, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1984; 323: 1311–5CrossRefGoogle Scholar
  6. 6.
    Malfertheiner P, Megraud F, O’Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56: 772–81PubMedCrossRefGoogle Scholar
  7. 7.
    Lassen A, Hallas J, Schaffalitzky de Muckadell OB. Com-plicated and uncomplicated peptic ulcers in a Danish county 1993–2002: a population-based cohort study. Am J Gastroenterol 2006; 101: 945–53PubMedCrossRefGoogle Scholar
  8. 8.
    Xia B, Xia HH, Ma CW, et al. Trends in the prevalence of peptic ulcer disease and Helicobacter pylori infection in family physician-referred uninvestigated dyspeptic patients in Hong Kong. Aliment Pharmacol Ther 2005; 22: 243–9PubMedCrossRefGoogle Scholar
  9. 9.
    Gabriel SE, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of non-steroidal anti-inflammatory drugs: a meta-analysis. Ann Intern Med 1991; 115: 787–96PubMedCrossRefGoogle Scholar
  10. 10.
    Garcia Rodriguez LA, Barreales TL. Risk of upper gastro-intestinal complications among users of traditional NSAIDs and COXIBs in the general population. Gastroenterology 2007; 132: 498–506PubMedCrossRefGoogle Scholar
  11. 11.
    Laine L, Hopkins RJ, Girardi LS. Has the impact of Heli-cobacter pylori therapy on ulcer recurrence in the United States been overstated? A meta-analysis of rigorously designed trials. Am J Gastroenterol 1998; 93: 1409–15PubMedGoogle Scholar
  12. 12.
    Jang HJ, Choi MH, Shin WG, et al. Has peptic ulcer disease changed during the past ten years in Korea? A prospective multicenter study. Dig Dis Sci 2008; 53: 1527–31PubMedCrossRefGoogle Scholar
  13. 13.
    Hung LC, Ching JY, Sung JJ, et al. Long-term outcome of Helicobacter pylori-negative idiopathic bleeding ulcers: a prospective cohort study. Gastroenterology 2005; 128: 1845–50PubMedCrossRefGoogle Scholar
  14. 14.
    Wong GL, Wong VW, Chan Y, et al. High incidence of mortality and recurrent bleeding in patients with Helicobacter pylori-negative idiopathic bleeding ulcers. Gastroenterology 2009; 137: 525–31PubMedCrossRefGoogle Scholar
  15. 15.
    Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494–502PubMedCrossRefGoogle Scholar
  16. 16.
    ACTIVE Investigators, Connolly SJ, Pogue J, et al. Effect of clopidogrel added to aspirin in patients with atrial fi-brillation. N Engl J Med 2009; 360: 2066–78PubMedCrossRefGoogle Scholar
  17. 17.
    Chey WD, Wong Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007 Aug; 102 (8): 1808–25PubMedCrossRefGoogle Scholar
  18. 18.
    Katelaris PH, Forbes GM, Talley NJ, et al. A randomized comparison of quadruple and triple therapies for Helicobacter pylori eradication: the QUADRATE study. Gastroenterology 2002; 123: 1763–9PubMedCrossRefGoogle Scholar
  19. 19.
    Gene E, Calvet X, Azagra R, et al. Triple vs. quadruple therapy for treating Helicobacter pylori infection: a meta-analysis. Aliment Pharmacol Ther 2003; 17: 1137–43CrossRefGoogle Scholar
  20. 20.
    Vakil N, Lanza F, Schwatrz H, et al. Seven-day therapy for Helicobacter pylori in the United States. Aliment Pharmacol Ther 2004; 20: 99–107PubMedCrossRefGoogle Scholar
  21. 21.
    Cardenas VM, Graham DY, el-Zimaity HM, et al. Rabeprazole containing triple therapy to eradicate Helicobacter pylori infection on the Texas-Mexican border. Aliment Pharmacol Ther 2006; 23: 295–301PubMedCrossRefGoogle Scholar
  22. 22.
    Calvet X, Garcia N, Lopez T, et al. A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther 2000; 14: 603–9PubMedCrossRefGoogle Scholar
  23. 23.
    Fuccio L, Minardi ME, Zagari RM, et al. Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication. Ann Intern Med 2007; 147: 553–62PubMedCrossRefGoogle Scholar
  24. 24.
    Gene E, Calvet X, Azagra R, et al. Triple vs. quadruple therapy for treating Helicobacter pylori infection: an updated meta-analysis. Aliment Pharmacol Ther 2003; 18: 543–4Google Scholar
  25. 25.
    Glupczynski Y, Megraud F, Lopez-Brea M, et al. European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. Eur J Clin Microbiol Infect Dis 2001; 20: 820–3PubMedCrossRefGoogle Scholar
  26. 26.
    Meyer JM, Silliman NP, Wang W, et al. Risk factors for Helicobacter pylori resistance in the United States: the Surveillance of H. pylori Antimicrobial Resistance Partnership (SHARP) study, 1993–1999. Ann Intern Med 2002; 136: 13–24Google Scholar
  27. 27.
    Duck WM, Sobel J, Pruckler JM, et al. Antimicrobial re-sistance incidence and risk factors among Helicobacter pylori-infected persons, United States. Emerg Infect Dis 2004; 10: 1088–94PubMedCrossRefGoogle Scholar
  28. 28.
    Tankovic J, Lamarque D, Lascols C, et al. Impact of Heli-cobacter pylori resistance to clarithromycin on the efficacy of the omeprazole-amoxicillin-clarithromycin therapy. Aliment Pharmacol Ther 2001; 15: 707–13PubMedCrossRefGoogle Scholar
  29. 29.
    Ducons JA, Santolaria S, Guirao R, et al. Impact of clari-thromycin resistance on the effectiveness of a regimen for Helicobacter pylori: a prospective study of 1-week lansoprazole, amoxycillin and clarithromycin in active peptic ulcer. Aliment Pharmacol Ther 1999; 13: 775–80PubMedCrossRefGoogle Scholar
  30. 30.
    Lee JH, Shin JH, Roe IH, et al. Impact of clarithromycin resistance on eradication of Helicobacter pylori in infected adults. Antimicrob Agents Chemother 2005; 49: 1600–3PubMedCrossRefGoogle Scholar
  31. 31.
    Megraud F, Lamouliatte H. Review article: the treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther 2003; 17: 1333–43PubMedCrossRefGoogle Scholar
  32. 32.
    Gisbert JP, Pajares JM. Helicobacter pylori “rescue” regimen when proton pump inhibitor-based triple therapies fail. Aliment Pharmacol Ther 2002; 16: 1047–57PubMedCrossRefGoogle Scholar
  33. 33.
    Gisbert JP, Morena F. Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure. Aliment Pharmacol Ther 2006; 23: 35–44PubMedCrossRefGoogle Scholar
  34. 34.
    Saad R, Schoenfeld P, Hyungjin MK, et al. Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis. Am J Gastroenterol 2006; 3: 488–96CrossRefGoogle Scholar
  35. 35.
    Qasim A, Sebastian S, Thornton O, et al. Rifabutin- and furazolidone-based Helicobacter pylori eradication therapies after failure of standard first- and second-line eradication attempts in dyspepsia patients. Aliment Pharmacol Ther 2005; 21: 91–6PubMedCrossRefGoogle Scholar
  36. 36.
    Nagahara A, Miwa H, Yamada T, et al. Five-day proton pump inhibitor-based quadruple therapy regimen is more effective than 7-day triple therapy regimen for Helicobacter pylori infection. Aliment Pharmacol Ther 2001; 15: 417–21PubMedCrossRefGoogle Scholar
  37. 37.
    Treiber G, Wittig J, Ammon S, et al. Clinical outcome and influencing factors of a new short-term quadruple therapy for Helicobacter pylori eradication: a randomized controlled trial (MACLOR study). Arch Intern Med 2002; 162: 153–60PubMedCrossRefGoogle Scholar
  38. 38.
    Wu DC, Hsu PI, Wu JY, et al. Sequential and concomitant therapy with 4 drugs are equally effective for eradication of H. pylori infection. Clin Gastroenterol Hepatol 2010; 8: 36–41CrossRefGoogle Scholar
  39. 39.
    Ueki N, Miyake K, Kusunoki M, et al. Impact of quadruple regimen of clarithromycin added to metronidazole-containing triple therapy against Helicobacter pylori infection following clarithromycin-containing triple-therapy failure. Helicobacter 2009; 14: 91–9PubMedCrossRefGoogle Scholar
  40. 40.
    Zullo A, Gatta L, De Francesco V, et al. High rate of Heli-cobacter pylori eradication with sequential therapy in elderly patients with peptic ulcer: a prospective controlled study. Aliment Pharmacol Ther 2005; 21: 1419–24PubMedCrossRefGoogle Scholar
  41. 41.
    Scaccianoce G, Hassan C, Panarese A, et al. Helicobacter pylori eradication with either 7-day or 10-day triple therapies, and with a 10-day sequential regimen. Can J Gastroenterol 2006; 20: 113–7PubMedGoogle Scholar
  42. 42.
    Vaira D, Zullo A, Vakil N, et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med 2007; 146: 556–63PubMedCrossRefGoogle Scholar
  43. 43.
    Francavilla R, Lionetti E, Castellaneta SP, et al. Improved efficacy of 10-day sequential treatment for Helicobacter pylori eradication in children: a randomized trial. Gastroenterology 2005; 129: 1414–9PubMedCrossRefGoogle Scholar
  44. 44.
    Choi WH, Park DI, Oh SJ, et al. Effectiveness of 10 day-sequential therapy for Helicobacter pylori eradication in Korea. Korean J Gastroenterol 2008; 51: 280–4PubMedGoogle Scholar
  45. 45.
    Sanchez-Delgado J, Calvet X, Bujanda L, et al. Ten-day sequential treatment for Helicobacter pylori eradication in clinical practice. Am J Gastroenterol 2008; 103: 2220–3PubMedCrossRefGoogle Scholar
  46. 46.
    Greenberg ER, Anderson GL, Morgan DR, et al. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomized trial. Lancet 2011; 378: 507–11PubMedCrossRefGoogle Scholar
  47. 47.
    Laine L. Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin North Am 1996; 6: 489–504Google Scholar
  48. 48.
    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: 1247–55Google Scholar
  49. 49.
    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: 1520–8PubMedCrossRefGoogle Scholar
  50. 50.
    Lanza FL, Chan FK, Quigley EM, et al. Guidelines for prevention of NSAID-related ulcer complications. Am J Gastroenterol 2009; 104 (3): 728–38PubMedCrossRefGoogle Scholar
  51. 51.
    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: 257–63PubMedCrossRefGoogle Scholar
  52. 52.
    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: 735–40PubMedCrossRefGoogle Scholar
  53. 53.
    Shorr RJ, Ray WA, Daugherty JR, et al. 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: 1665–70PubMedCrossRefGoogle Scholar
  54. 54.
    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: 241–9PubMedCrossRefGoogle Scholar
  55. 55.
    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 anti-inflammatory drug use. Am J Gastroenterol 2005; 100: 1685–93PubMedCrossRefGoogle Scholar
  56. 56.
    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: 1411–8PubMedCrossRefGoogle Scholar
  57. 57.
    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: 9–13PubMedCrossRefGoogle Scholar
  58. 58.
    Goldstein JL, Johanson JF, Hawkey CJ, et al. Clinical trial: healing of NSAID-associated gastric ulcers in patients continuing NSAID therapy. A randomized study comparing ranitidine with esomeprazole. Aliment Pharmacol Ther 2007; 26: 1101–11CrossRefGoogle Scholar
  59. 59.
    Rostom A, Dube C, Wells G, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002; (4): CD002296Google Scholar
  60. 60.
    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: iii-iv; 1-164Google Scholar
  61. 61.
    Rostom A, Muir K, Dube’ C, et al. Gastrointestinal safety of cyclooxygenase-2 inhibitors: a Cochrane Collaboration systematic review. Clin Gastroenterol Hepatol 2007; 5: 818–28PubMedCrossRefGoogle Scholar
  62. 62.
    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: 967–73PubMedCrossRefGoogle Scholar
  63. 63.
    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: 228–1732PubMedCrossRefGoogle Scholar
  64. 64.
    Targownik LE, Metge CJ, Leung S, et al. The relative effi-cacies of gastro-protective strategies in chronic users of nonsteroidal anti-inflammatory drugs. Gastroenterology 2008; 134: 937–44PubMedCrossRefGoogle Scholar
  65. 65.
    Graham DY, Agrawal NM, Roth SH. Prevention of NSAID-induced gastric ulcer with misoprostol: multicenter, double-blind placebo-controlled trial. Lancet 1988; 2: 1277–80PubMedCrossRefGoogle Scholar
  66. 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: 344–50PubMedCrossRefGoogle Scholar
  67. 67.
    Graham DY, Agrawal NM, Campbell DR, et al. Ulcer pre-vention in long-term users of nonsteroidal anti-inflammatory drugs: results of a double-blind, randomized, multicenter, active- and placebo-controlled study of misoprostol vs. lanso-prazole. Arch Intern Med 2002; 162: 160–75Google Scholar
  68. 68.
    Brown TJ, Hooper L, Elliott RA, et al. A comparison of the cost-effectiveness of five strategies for the prevention of non-steroidal anti-inflammatory drug-induced gastrointestinal toxicity: a systematic review with economic modeling. Health Technol Assess 2006; 10: iii–iv, xi–xiii, 1-183Google Scholar
  69. 69.
    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: 1038–43Google Scholar
  70. 70.
    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: 1621–6PubMedCrossRefGoogle Scholar
  71. 71.
    Kearney PM, Baigent C, Godwin J, et al. Do selective cyclooxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomized trials. BMJ 2006; 332: 1302–8PubMedCrossRefGoogle Scholar
  72. 72.
    McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclo-oxygenase 2. JAMA 2006; 296: 1633–44PubMedCrossRefGoogle Scholar
  73. 73.
    Solomon SD, Wittes J, Finn PV, et al. Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis. Circulation 2008; 117: 2104–13PubMedCrossRefGoogle Scholar
  74. 74.
    Chan FK, Abraham NS, Scheiman JM, et al. First Inter-national Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Antiplatelet Agents. Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Antiplatelet Agents. Am J Gastroenterol 2008; 103: 2908–18Google Scholar
  75. 75.
    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: 779–86PubMedCrossRefGoogle Scholar
  76. 76.
    Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. Lancet 2009; 374: 1449–61PubMedCrossRefGoogle Scholar
  77. 77.
    Moukarbel GV, Signorovitch JE, Pfeffer MA, et al. Gastro-intestinal bleeding in high risk survivors of myocardial in-farction: the VALIANT Trial. Eur Heart J 2009; 30: 2226–32PubMedCrossRefGoogle Scholar
  78. 78.
    Lai Lam SK, Chu KM, et al. Lansoprazole for the pre-vention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 2002; 346: 2033–8CrossRefGoogle Scholar
  79. 79.
    Chan FKL, Ching J, Suen B-Y, et al. Effect of H. pylori eradication on the long-term incidence of recurrent ulcer bleeding in high-risk aspirin users: a 10-year prospective cohort study. Gastroenterology 2011; 140 (5): S173-4Google Scholar
  80. 80.
    Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: summary article. A report of the American College of Cardiology/American Heart Association task force on practice guidelines. J Am Coll Cardiol 2002; 40: 1366–74CrossRefGoogle Scholar
  81. 81.
    Chan FK, Ching JY, Hung LC, et al. Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. N Engl J Med 2005; 352: 238–44PubMedCrossRefGoogle Scholar
  82. 82.
    Lai Chu KM, Hui WM, et al. Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications. Clin Gastroenterol Hepatol 2006; 4: 860–5CrossRefGoogle Scholar
  83. 83.
    Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol 2008; 52: 1502–17PubMedCrossRefGoogle Scholar
  84. 84.
    Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med 2010; 363: 1909–17PubMedCrossRefGoogle Scholar
  85. 85.
    Gilard M, Arnaud Cornily JC, et al. Influence of ome-prazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole Clopidogrel Aspirin) study. J Am Coll Cardiol 2008; 51: 256–60PubMedCrossRefGoogle Scholar
  86. 86.
    Li XQ, Andersson TB, Ahlstrom M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004; 32: 821–7PubMedCrossRefGoogle Scholar
  87. 87.
    Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009; 180: 713–8PubMedGoogle Scholar
  88. 88.
    Ho PM, Maddox TM, Wang L, et al. Risk of adverse out-comes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301: 937–44PubMedCrossRefGoogle Scholar
  89. 89.
    Kwok CS, Loke YK. Meta-analysis: the effects of proton pump inhibitors on cardiovascular events and mortality in patients receiving clopidogrel. Aliment Pharmacol Ther 2010; 31: 810–23PubMedGoogle Scholar
  90. 90.
    Becker RC, Scheiman J, Dauerman HL et al. Management of platelet-directed pharmacotherapy in patients with atherosclerotic coronary artery disease undergoing elective endoscopic gastrointestinal procedures. J Am Coll Cardiol 2009; 54: 2261–76PubMedCrossRefGoogle Scholar
  91. 91.
    Chan FK. Anti-platelet therapy and managing ulcer risk. J Gastroenterol Hepatol 2012; 27: 195–9PubMedCrossRefGoogle Scholar
  92. 92.
    Ciociola AA, McSorley DJ, Turner K, et al. Helicobacter pylori infection rates in duodenal ulcer patients in the United States may be lower than previously estimated. Am J Gastroenterol 1999; 94: 1834–40PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2012

Authors and Affiliations

  1. 1.Institute of Digestive DiseaseThe Chinese University of Hong Kong, Prince of Wales HospitalShatin, New TerritoriesHong Kong

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