Abstract
Despite the major advances in the treatment of peptic ulcer disease, its complication in the elderly has increased. This is because of the increasing use of non-steroidal anti-inflammatory drugs, and the high prevalence of Helicobacter pylori infection. The presentation of peptic ulcers in the elderly patients can be subtle, and late presentation with upper gastrointestinal bleeding of peptic ulcers is not uncommon in the elderly population. The aim of this article is to review the current treatment options for upper gastrointestinal bleeding, and to discuss the place of drug therapy in both the acute and ongoing management of individual patients. Its focus will be on the benefits and risks of each option in the elderly. There is significant evidence to suggest that anti-secretory medications are useful in the treatment of peptic ulcers and associated complications in the elderly. Although a large number of studies have reported potential adverse effects of proton pump inhibitors, this evidence comes from retrospective observational studies, and such reports should be regarded with caution, and randomized controlled studies are required to confirm or refute these results. Nonetheless, it will be important to practice the appropriate use of acid suppression therapy, and identify which patients will gain maximum benefit from proton pump inhibitor therapy.
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References
Bardhan KD, Cust G, Hinchliffe RF, et al. Changing pattern of admissions and operations for duodenal ulcer. Br J Surg. 1989;76:230–6.
Higham J, Kang JY, Majeed A. Recent trends in admissions and mortality due to peptic ulcer in England: increasing frequency of haemorrhage among older subjects. Gut. 2002;50:460–4.
Newton JL. Improving the gastrointestinal tolerability of aspirin in older people. Clin Interv Aging. 2006;1:33–9.
Cryer B, Lee E, Feldman M. Factors influencing gastroduodenal mucosal prostaglandin concentrations: roles of smoking and aging. Ann Intern Med. 1992;116:636–40.
Goto H, Sugiyama S, Ohara A, et al. Age-associated decreases in prostaglandin contents in human gastric mucosa. Biochem Biophys Res Commun. 1992;186:1443–8.
Guslandi M, Pellegrini A, Sorghi M. Gastric mucosal defences in the elderly. Gerontology. 1999;45:206–8.
Kim SW, Parekh D, Townsend CM, Jr, et al. Effects of aging on duodenal bicarbonate secretion. Ann Surg. 1990;212:332–7 (discussion 337–8).
Brogna A, Ferrara R, Bucceri AM, et al. Influence of aging on gastrointestinal transit time: an ultrasonographic and radiologic study. Invest Radiol. 1999;34:357–9.
Rockall TA, Logan RF, Devlin HB, et al. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom: Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. BMJ. 1995;311:222–6.
Seinela L, Ahvenainen J. Peptic ulcer in the very old patients. Gerontology. 2000;46:271–5.
Kemppainen H, Raiha I, Sourander L. Clinical presentation of peptic ulcer in the elderly. Gerontology. 1997;43:283–8.
Pilotto A, Maggi S, Noale M, et al. Development and validation of a new questionnaire for the evaluation of upper gastrointestinal symptoms in the elderly population: a multicenter study. J Gerontol A Biol Sci Med Sci. 2010;65:174–8.
de Manzoni G, Catalano F, Festini M, et al. Acute hemorrhage caused by duodenal ulcer: results of endoscopic treatment of the first bleeding episode and of recurrences. Ann Ital Chir. 2002;73:387–94 (discussion 394–6).
Carbonell N, Pauwels A, Serfaty L, et al. Erythromycin infusion prior to endoscopy for acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Am J Gastroenterol. 2006;101:1211–5.
Coffin B, Pocard M, Panis Y, et al. Erythromycin improves the quality of EGD in patients with acute upper GI bleeding: a randomized controlled study. Gastrointest Endosc. 2002;56:174–9.
Frossard JL, Spahr L, Queneau PE, et al. Erythromycin intravenous bolus infusion in acute upper gastrointestinal bleeding: a randomized, controlled, double-blind trial. Gastroenterology. 2002;123:17–23.
Barkun AN, Bardou M, Martel M, et al. Prokinetics in acute upper GI bleeding: a meta-analysis. Gastrointest Endosc. 2010;72:1138–45.
Pateron D, Vicaut E, Debuc E, et al. Erythromycin infusion or gastric lavage for upper gastrointestinal bleeding: a multicenter randomized controlled trial. Ann Emerg Med. 2011;57:582–9.
Lau JY, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med. 2007;356:1631–40.
Sreedharan A, Martin J, Leontiadis GI, et al. Proton pump inhibitor treatment initiated prior to endoscopic diagnosis in upper gastrointestinal bleeding. Cochrane Database Syst Rev. 2010;(7):CD005415.
Laine L, McQuaid KR. Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol. 2009;7:33–47 (quiz 1–2).
Neumann I, Letelier LM, Rada G, et al. Comparison of different regimens of proton pump inhibitors for acute peptic ulcer bleeding. Cochrane Database Syst Rev. 2013;6:CD007999.
Tsoi KK, Hirai HW, Sung JJ. Meta-analysis: comparison of oral vs. intravenous proton pump inhibitors in patients with peptic ulcer bleeding. Aliment Pharmacol Ther. 2013;38:721–8.
Laine L, Peterson WL. Bleeding peptic ulcer. N Engl J Med. 1994;331:717–27.
Laporte JR, Carne X, Vidal X, et al. Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal anti-inflammatory drugs: Catalan Countries Study on Upper Gastrointestinal Bleeding. Lancet. 1991;337:85–9.
Visser LE, Graatsma HH, Stricker BH. Contraindicated NSAIDs are frequently prescribed to elderly patients with peptic ulcer disease. Br J Clin Pharmacol. 2002;53:183–8.
Chan FK, Hung LC, Suen BY, 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.
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, randomised trial. Lancet. 2007;369:1621–6.
Sung JJ, Chan FK, Chen M, et al. Asia-Pacific Working Group consensus on non-variceal upper gastrointestinal bleeding. Gut. 2011;60:1170–7.
Sung JJ, Lau JY, Ching JY, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Ann Intern Med. 2010;152:1–9.
Lau JY, Barkun A, Fan DM, et al. Challenges in the management of acute peptic ulcer bleeding. Lancet. 2013;381:2033–43.
Airoldi F, Colombo A, Morici N, et al. Incidence and predictors of drug-eluting stent thrombosis during and after discontinuation of thienopyridine treatment. Circulation. 2007;116:745–54.
Pilotto A, Franceschi M, Leandro G, et al. Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther. 2004;20:1091–7.
Bianchi Porro G, Lazzaroni M, Petrillo M, et al. Prevention of gastroduodenal damage with omeprazole in patients receiving continuous NSAIDs treatment: a double blind placebo controlled study. Ital J Gastroenterol Hepatol. 1998;30:43–7.
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 randomised, double blind, placebo controlled, clinical trial. Gut. 2002;51:329–35.
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.
Rostom A, Dube C, Wells G, et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev. 2002;(4):CD002296.
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;338:719–26.
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;338:727–34.
Stupnicki T, Dietrich K, Gonzalez-Carro P, et al. Efficacy and tolerability of pantoprazole compared with misoprostol for the prevention of NSAID-related gastrointestinal lesions and symptoms in rheumatic patients. Digestion. 2003;68:198–208.
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.
Yeomans N, Lanas A, Labenz J, et al. Efficacy of esomeprazole (20 mg once daily) for reducing the risk of gastroduodenal ulcers associated with continuous use of low-dose aspirin. Am J Gastroenterol. 2008;103:2465–73.
Ng FH, Wong SY, Lam KF, et al. Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions. Gastroenterology. 2010;138:82–8.
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.
Wang X, Tian HJ, Yang HK, et al. Meta-analysis: cyclooxygenase-2 inhibitors are no better than nonselective nonsteroidal anti-inflammatory drugs with proton pump inhibitors in regard to gastrointestinal adverse events in osteoarthritis and rheumatoid arthritis. Eur J Gastroenterol Hepatol. 2011;23:876–80.
Pilotto A. Helicobacter pylori-associated peptic ulcer disease in older patients: current management strategies. Drugs Aging. 2001;18:487–94.
Pilotto A, Franceschi M, Di Mario F, et al. The long-term clinical outcome of elderly patients with Helicobacter pylori-associated peptic ulcer disease. Gerontology. 1998;44:153–8.
Salles N, Megraud F. Current management of Helicobacter pylori infections in the elderly. Expert Rev Anti Infect Ther. 2007;5:845–56.
Pilotto A, Franceschi M, Leandro G, et al. Cure of Helicobacter pylori infection in elderly patients: comparison of low versus high doses of clarithromycin in combination with amoxicillin and pantoprazole. Aliment Pharmacol Ther. 2001;15:1031–6.
Pilotto A, Franceschi M, Perri F, et al. Treatment options for Helicobacter pylori infection in the elderly. Aging Health. 2006;2:661.
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;136:13–24.
Lee M, Kemp JA, Canning A, et al. A randomized controlled trial of an enhanced patient compliance program for Helicobacter pylori therapy. Arch Intern Med. 1999;159:2312–6.
Ishihara M, Ito M. Influence of aging on gastric ulcer healing activities of cimetidine and omeprazole. Eur J Pharmacol. 2002;444:209–15.
Berardi RR. A critical evaluation of proton pump inhibitors in the treatment of gastroesophageal reflux disease. Am J Manag Care. 2000;6:S491–505.
Maggio M, Corsonello A, Ceda GP, et al. Proton pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med. 2013;173:518–23.
Zink DA, Pohlman M, Barnes M, et al. Long-term use of acid suppression started inappropriately during hospitalization. Aliment Pharmacol Ther. 2005;21:1203–9.
Gupta R, Garg P, Kottoor R, et al. Overuse of acid suppression therapy in hospitalized patients. South Med J. 2010;103:207–11.
Walker KJ, Gilliland SS, Vance-Bryan K, et al. Clostridium difficile colonization in residents of long-term care facilities: prevalence and risk factors. J Am Geriatr Soc. 1993;41:940–6.
Williams C, McColl KE. Review article: proton pump inhibitors and bacterial overgrowth. Aliment Pharmacol Ther. 2006;23:3–10.
Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102:2047–56 (quiz 2057).
Janarthanan S, Ditah I, Kutait A. A meta-analysis of 16 observational studies on proton pump inhibitor use and risk of Clostridium difficile associated diarrhea. Am J Gastroenterol. 2010;105:S139.
Shukla S, Shukla A, Guha S. Use of proton pump inhibitors and risk of Clostridium difficile-associated diarrhea: a meta-analysis. Gastroenterology. 2010;138:209.
Deshpande A, Pant C, Pasupuleti V, et al. Association between proton pump inhibitor therapy and Clostridium difficile infection in a meta-analysis. Clin Gastroenterol Hepatol. 2012;10:225–33.
Thomson AB, Sauve MD, Kassam N, et al. Safety of the long-term use of proton pump inhibitors. World J Gastroenterol. 2010;16:2323–30.
Thorens J, Froehlich F, Schwizer W, et al. Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study. Gut. 1996;39:54–9.
Altman KW, Waltonen JD, Hammer ND, et al. Proton pump (H+/K+-ATPase) expression in human laryngeal seromucinous glands. Otolaryngol Head Neck Surg. 2005;133:718–24.
Johnstone J, Nerenberg K, Loeb M. Meta-analysis: proton pump inhibitor use and the risk of community-acquired pneumonia. Aliment Pharmacol Ther. 2010;31:1165–77.
Eom CS, Jeon CY, Lim JW, et al. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183:310–9.
Giuliano C, Wilhelm SM, Kale-Pradhan PB. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev Clin Pharmacol. 2012;5:337–44.
O’Connell MB, Madden DM, Murray AM, et al. Effects of proton pump inhibitors on calcium carbonate absorption in women: a randomized crossover trial. Am J Med. 2005;118:778–81.
Mizunashi K, Furukawa Y, Katano K, et al. Effect of omeprazole, an inhibitor of H+, K(+)-ATPase, on bone resorption in humans. Calcif Tissue Int. 1993;53:21–5.
Ngamruengphong S, Leontiadis GI, Radhi S, et al. Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2011;106:1209–18 (quiz 1219).
Kwok CS, Yeong JK, Loke YK. Meta-analysis: risk of fractures with acid-suppressing medication. Bone. 2011;48:768–76.
Ye X, Liu H, Wu C, et al. Proton pump inhibitors therapy and risk of hip fracture: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol. 2011;23:794–800.
Famularo G, Gasbarrone L, Minisola G. Hypomagnesemia and proton-pump inhibitors. Expert Opin Drug Saf. 2013;12:709–16.
Koop H, Bachem MG. Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy. J Clin Gastroenterol. 1992;14:288–92.
Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr. 1999;19:357–77.
Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 absorption. J Am Coll Nutr. 1994;13:584–91.
Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin (vitamin B12). Ann Intern Med. 1994;120:211–5.
Hirschowitz BI, Worthington J, Mohnen J. Vitamin B12 deficiency in hypersecretors during long-term acid suppression with proton pump inhibitors. Aliment Pharmacol Ther. 2008;27:1110–21.
Dharmarajan TS, Kanagala MR, Murakonda P, et al. Do acid-lowering agents affect vitamin B12 status in older adults? J Am Med Dir Assoc. 2008;9:162–7.
Dharmarajan TS, Norkus EP. Does long-term PPI use result in vitamin B12 deficiency in elderly individuals? Nat Clin Pract Gastroenterol Hepatol. 2008;5:604–5.
Cook DJ, Reeve BK, Guyatt GH, et al. Stress ulcer prophylaxis in critically ill patients: resolving discordant meta-analyses. JAMA. 1996;275:308–14.
Messori A, Trippoli S, Vaiani M, et al. Bleeding and pneumonia in intensive care patients given ranitidine and sucralfate for prevention of stress ulcer: meta-analysis of randomised controlled trials. BMJ. 2000;321:1103–6.
Christensen K, Doblhammer G, Rau R, et al. Ageing populations: the challenges ahead. Lancet. 2009;374:1196–208.
Ornstein SM, Nietert PJ, Jenkins RG, et al. The prevalence of chronic diseases and multimorbidity in primary care practice: a PPRNet report. J Am Board Fam Med. 2013;26:518–24.
Spinewine A, Schmader KE, Barber N, et al. Appropriate prescribing in elderly people: how well can it be measured and optimised? Lancet. 2007;370:173–84.
Sergi G, De Rui M, Sarti S, et al. Polypharmacy in the elderly: can comprehensive geriatric assessment reduce inappropriate medication use? Drugs Aging. 2011;28:509–18.
Rochon PA, Gurwitz JH. Optimising drug treatment for elderly people: the prescribing cascade. BMJ. 1997;315:1096–9.
Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. 2005;353:487–97.
Mangoni AA, Jackson SH. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004;57:6–14.
Simonson W, Feinberg JL. Medication-related problems in the elderly: defining the issues and identifying solutions. Drugs Aging. 2005;22:559–69.
Department of Health. Medicines and older people: implementing medicines-related aspects of the NSF for older people; 2001. http://www.hcsu.org.uk/index.php?option=com_docman&task=doc_download&gid=322%20. Accessed Feb 2014.
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Both Prof. Chan and Dr. Kyaw declare that they have no significant competing financial, professional, or personal interests that might have influenced the performance or presentation of the work described in this manuscript.
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Kyaw, M.H., Chan, F.K.L. Pharmacologic Options in the Management of Upper Gastrointestinal Bleeding: Focus on the Elderly. Drugs Aging 31, 349–361 (2014). https://doi.org/10.1007/s40266-014-0173-5
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DOI: https://doi.org/10.1007/s40266-014-0173-5