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Published in: European Journal of Epidemiology 1/2015

01-01-2015 | Review

Prophylactic use of aspirin: systematic review of harms and approaches to mitigation in the general population

Authors: Mangesh A. Thorat, Jack Cuzick

Published in: European Journal of Epidemiology | Issue 1/2015

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Abstract

A careful assessment of benefits and harms is required to assess suitability of aspirin as a prophylactic public health measure. However, comprehensive population-level data on harms are lacking. We collected and synthesized age and sex-specific data on harms relevant to aspirin use in average-risk individuals aged 50 years or older. We conducted systematic literature searches to identify baseline rates of gastrointestinal (GI) bleeding, peptic ulcer, major extra-cranial bleeding, and case-fatality rates due to GI bleeding or peptic ulcer in general population. The magnitude of aspirin-associated increase, the prevalence and attributable risk of Helicobacter pylori infection on these events in aspirin users was also assessed. Baseline rates of major extracranial bleeding events and GI complications increase with age; an almost threefold to fourfold increase is observed from age 50–54 to 70–74 years. Low or standard-dose aspirin use increases GI bleeding events by 60 % leading to an annual excess of 0.45 and 0.79 GI bleeding events per 1,000 women and men aged 50–54 years respectively. 5–10 % of major GI complications are fatal; a clear age dependence—higher fatality in older individuals, is seen. Eradication of H. pylori infection before aspirin use could reduce the incidence of upper GI complications by 25–30 %. GI complications are increased by about 60 % due to aspirin use but are fatal only in a very small proportion of individuals younger than 70 years of age. Major bleeding events that are comparable in severity to cancer or CVD, are infrequent. Screening and eradication of H. pylori infection could substantially lower aspirin-related GI harms.
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Literature
3.
9.
go back to reference Cuzick J, Thorat MA, Bosetti C, et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol. 2014;. doi:10.1093/annonc/mdu225. Cuzick J, Thorat MA, Bosetti C, et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol. 2014;. doi:10.​1093/​annonc/​mdu225.
11.
go back to reference Office for National Statistics. Mortality statistics: deaths registered in 2008. National Statistics London; 2009. Office for National Statistics. Mortality statistics: deaths registered in 2008. National Statistics London; 2009.
13.
go back to reference Garcia Rodriguez LA, Hernandez-Diaz S. Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Am J Epidemiol. 2004;159(1):23–31. doi:10.1093/aje/kwh005.CrossRefPubMed Garcia Rodriguez LA, Hernandez-Diaz S. Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs. Am J Epidemiol. 2004;159(1):23–31. doi:10.​1093/​aje/​kwh005.CrossRefPubMed
15.
go back to reference Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60. doi:10.1016/S0140-6736(09)60503-1.CrossRefPubMed Baigent C, Blackwell L, Collins R, et al. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373(9678):1849–60. doi:10.​1016/​S0140-6736(09)60503-1.CrossRefPubMed
17.
go back to reference Garcia Rodriguez LA, Ruigomez A, Hasselgren G, Wallander MA, Johansson S. Comparison of mortality from peptic ulcer bleed between patients with or without peptic ulcer antecedents. Epidemiology. 1998;9(4):452–6.CrossRefPubMed Garcia Rodriguez LA, Ruigomez A, Hasselgren G, Wallander MA, Johansson S. Comparison of mortality from peptic ulcer bleed between patients with or without peptic ulcer antecedents. Epidemiology. 1998;9(4):452–6.CrossRefPubMed
18.
go back to reference Hasselgren G, Blomqvist A, Eriksson S, Henningsson A, Lundell L. Short and long term course of elderly patients with peptic ulcer bleeding—analysis of factors influencing fatal outcome. Eur J Surg. 1998;164(9):685–91. doi:10.1080/110241598750005570.CrossRefPubMed Hasselgren G, Blomqvist A, Eriksson S, Henningsson A, Lundell L. Short and long term course of elderly patients with peptic ulcer bleeding—analysis of factors influencing fatal outcome. Eur J Surg. 1998;164(9):685–91. doi:10.​1080/​1102415987500055​70.CrossRefPubMed
20.
go back to reference Lanas A, Garcia-Rodriguez LA, Polo-Tomas M, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol. 2009;104(7):1633–41. doi:10.1038/ajg.2009.164.CrossRefPubMed Lanas A, Garcia-Rodriguez LA, Polo-Tomas M, et al. Time trends and impact of upper and lower gastrointestinal bleeding and perforation in clinical practice. Am J Gastroenterol. 2009;104(7):1633–41. doi:10.​1038/​ajg.​2009.​164.CrossRefPubMed
21.
go back to reference Morales Uribe CH, Sierra Sierra S, Hernandez Hernandez AM, Arango Durango AF, Lopez GA. Upper gastrointestinal bleeding: risk factors for mortality in two urban centres in Latin America. Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva. 2011;103(1):20–4. Morales Uribe CH, Sierra Sierra S, Hernandez Hernandez AM, Arango Durango AF, Lopez GA. Upper gastrointestinal bleeding: risk factors for mortality in two urban centres in Latin America. Revista espanola de enfermedades digestivas: organo oficial de la Sociedad Espanola de Patologia Digestiva. 2011;103(1):20–4.
22.
go back to reference Paspatis GA, Matrella E, Kapsoritakis A, et al. An epidemiological study of acute upper gastrointestinal bleeding in Crete, Greece. Eur J Gastroenterol Hepatol. 2000;12(11):1215–20.CrossRefPubMed Paspatis GA, Matrella E, Kapsoritakis A, et al. An epidemiological study of acute upper gastrointestinal bleeding in Crete, Greece. Eur J Gastroenterol Hepatol. 2000;12(11):1215–20.CrossRefPubMed
23.
go back to reference Hearnshaw SA, Logan RF, Lowe D, Travis SP, Murphy MF, Palmer KR. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. Gut. 2011;60(10):1327–35. doi:10.1136/gut.2010.228437.CrossRefPubMed Hearnshaw SA, Logan RF, Lowe D, Travis SP, Murphy MF, Palmer KR. Acute upper gastrointestinal bleeding in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK audit. Gut. 2011;60(10):1327–35. doi:10.​1136/​gut.​2010.​228437.CrossRefPubMed
26.
27.
29.
33.
38.
go back to reference de Abajo FJ, Gil MJ, Bryant V, Timoner J, Oliva B, Garcia-Rodriguez LA. Upper gastrointestinal bleeding associated with NSAIDs, other drugs and interactions: a nested case-control study in a new general practice database. Eur J Clin Pharmacol. 2013;69(3):691–701. doi:10.1007/s00228-012-1386-3.CrossRefPubMed de Abajo FJ, Gil MJ, Bryant V, Timoner J, Oliva B, Garcia-Rodriguez LA. Upper gastrointestinal bleeding associated with NSAIDs, other drugs and interactions: a nested case-control study in a new general practice database. Eur J Clin Pharmacol. 2013;69(3):691–701. doi:10.​1007/​s00228-012-1386-3.CrossRefPubMed
40.
41.
go back to reference 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(12):1731–8. doi:10.1136/gut.2005.080754.CrossRefPubMedCentralPubMed 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(12):1731–8. doi:10.​1136/​gut.​2005.​080754.CrossRefPubMedCentralPubMed
42.
43.
go back to reference Sapoznikov B, Vilkin A, Hershkovici M, Fishman M, Eliakim R, Niv Y. Minidose aspirin and gastrointestinal bleeding—a retrospective, case–control study in hospitalized patients. Dig Dis Sci. 2005;50(9):1621–4. doi:10.1007/s10620-005-2906-0.CrossRefPubMed Sapoznikov B, Vilkin A, Hershkovici M, Fishman M, Eliakim R, Niv Y. Minidose aspirin and gastrointestinal bleeding—a retrospective, case–control study in hospitalized patients. Dig Dis Sci. 2005;50(9):1621–4. doi:10.​1007/​s10620-005-2906-0.CrossRefPubMed
46.
go back to reference Pilotto A, Franceschi M, Leandro G, et al. The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs. Aging Clin Exp Res. 2003;15(6):494–9.CrossRefPubMed Pilotto A, Franceschi M, Leandro G, et al. The risk of upper gastrointestinal bleeding in elderly users of aspirin and other non-steroidal anti-inflammatory drugs: the role of gastroprotective drugs. Aging Clin Exp Res. 2003;15(6):494–9.CrossRefPubMed
51.
go back to reference Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840. doi:10.1136/bmj.a1840.CrossRefPubMedCentralPubMed Belch J, MacCuish A, Campbell I, et al. The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840. doi:10.​1136/​bmj.​a1840.CrossRefPubMedCentralPubMed
53.
go back to reference Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010;303(9):841–8. doi:10.1001/jama.2010.221.CrossRefPubMed Fowkes FG, Price JF, Stewart MC, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010;303(9):841–8. doi:10.​1001/​jama.​2010.​221.CrossRefPubMed
54.
go back to reference The Medical Research Council’s General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The medical research council’s general practice research framework. Lancet. 1998;351(9098):233–41. doi:10.1016/S0140-6736(97)11475-1.CrossRef The Medical Research Council’s General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. The medical research council’s general practice research framework. Lancet. 1998;351(9098):233–41. doi:10.​1016/​S0140-6736(97)11475-1.CrossRef
55.
go back to reference Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. HOT study group. Lancet. 1998;351(9118):1755–62. doi:10.1016/S0140-6736(98)04311-6.CrossRefPubMed Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the hypertension optimal treatment (HOT) randomised trial. HOT study group. Lancet. 1998;351(9118):1755–62. doi:10.​1016/​S0140-6736(98)04311-6.CrossRefPubMed
56.
57.
go back to reference Peto R, Gray R, Collins R, et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed). 1988;296(6618):313–6.CrossRef Peto R, Gray R, Collins R, et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed). 1988;296(6618):313–6.CrossRef
58.
59.
60.
61.
go back to reference Harvey RF, Spence RW, Lane JA, et al. Relationship between the birth cohort pattern of Helicobacter pylori infection and the epidemiology of duodenal ulcer. QJM Mon J Assoc Phys. 2002;95(8):519–25. Harvey RF, Spence RW, Lane JA, et al. Relationship between the birth cohort pattern of Helicobacter pylori infection and the epidemiology of duodenal ulcer. QJM Mon J Assoc Phys. 2002;95(8):519–25.
64.
66.
go back to reference Mathers C, Fat DM, Boerma JT, World Health Organization. The global burden of disease: 2004 update. Geneva: World Health Organization; 2008. Mathers C, Fat DM, Boerma JT, World Health Organization. The global burden of disease: 2004 update. Geneva: World Health Organization; 2008.
67.
go back to reference Rothwell PM, Price JF, Fowkes FG, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379(9826):1602–12. doi:10.1016/S0140-6736(11)61720-0.CrossRefPubMed Rothwell PM, Price JF, Fowkes FG, et al. Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet. 2012;379(9826):1602–12. doi:10.​1016/​S0140-6736(11)61720-0.CrossRefPubMed
69.
go back to reference Graham DY, Smith JL, Spjut HJ, Torres E. Gastric adaptation. Studies in humans during continuous aspirin administration. Gastroenterology. 1988;95(2):327–33.PubMed Graham DY, Smith JL, Spjut HJ, Torres E. Gastric adaptation. Studies in humans during continuous aspirin administration. Gastroenterology. 1988;95(2):327–33.PubMed
70.
go back to reference Graham DY, Smith JL, Dobbs SM. Gastric adaptation occurs with aspirin administration in man. Dig Dis Sci. 1983;28(1):1–6.CrossRefPubMed Graham DY, Smith JL, Dobbs SM. Gastric adaptation occurs with aspirin administration in man. Dig Dis Sci. 1983;28(1):1–6.CrossRefPubMed
71.
go back to reference Kawai T, Yamagishi T, Goto S. Circadian variations of gastrointestinal mucosal damage detected with transnasal endoscopy in apparently healthy subjects treated with low-dose aspirin (ASA) for a short period. J Atheroscler Thromb. 2009;16(3):155–63. doi:10.5551/jat.E615.CrossRefPubMed Kawai T, Yamagishi T, Goto S. Circadian variations of gastrointestinal mucosal damage detected with transnasal endoscopy in apparently healthy subjects treated with low-dose aspirin (ASA) for a short period. J Atheroscler Thromb. 2009;16(3):155–63. doi:10.​5551/​jat.​E615.CrossRefPubMed
73.
go back to reference Shiotani A, Haruma K, Nishi R, et al. Randomized, double-blind, pilot study of geranylgeranylacetone versus placebo in patients taking low-dose enteric-coated aspirin. Low-dose aspirin-induced small bowel damage. Scand J Gastroenterol. 2010;45(3):292–8. doi:10.3109/00365520903453182.CrossRefPubMed Shiotani A, Haruma K, Nishi R, et al. Randomized, double-blind, pilot study of geranylgeranylacetone versus placebo in patients taking low-dose enteric-coated aspirin. Low-dose aspirin-induced small bowel damage. Scand J Gastroenterol. 2010;45(3):292–8. doi:10.​3109/​0036552090345318​2.CrossRefPubMed
74.
go back to reference Endo H, Sakai E, Higurashi T, et al. Differences in the severity of small bowel mucosal injury based on the type of aspirin as evaluated by capsule endoscopy. Dig Liver Dis Off J Italian Soc Gastroenterol Italian Assoc Study Liver. 2012;44(10):833–8. doi:10.1016/j.dld.2012.05.016.CrossRef Endo H, Sakai E, Higurashi T, et al. Differences in the severity of small bowel mucosal injury based on the type of aspirin as evaluated by capsule endoscopy. Dig Liver Dis Off J Italian Soc Gastroenterol Italian Assoc Study Liver. 2012;44(10):833–8. doi:10.​1016/​j.​dld.​2012.​05.​016.CrossRef
76.
go back to reference Endo H, Hosono K, Inamori M, et al. Characteristics of small bowel injury in symptomatic chronic low-dose aspirin users: the experience of two medical centers in capsule endoscopy. J Gastroenterol. 2009;44(6):544–9. doi:10.1007/s00535-009-0040-z.CrossRefPubMed Endo H, Hosono K, Inamori M, et al. Characteristics of small bowel injury in symptomatic chronic low-dose aspirin users: the experience of two medical centers in capsule endoscopy. J Gastroenterol. 2009;44(6):544–9. doi:10.​1007/​s00535-009-0040-z.CrossRefPubMed
81.
go back to reference Naja F, Kreiger N, Sullivan T. Helicobacter pylori infection in Ontario: prevalence and risk factors. Canadian journal of gastroenterology. J Can de gastroenterol. 2007;21(8):501–6. Naja F, Kreiger N, Sullivan T. Helicobacter pylori infection in Ontario: prevalence and risk factors. Canadian journal of gastroenterology. J Can de gastroenterol. 2007;21(8):501–6.
82.
go back to reference Zajacova A, Dowd JB, Aiello AE. Socioeconomic and race/ethnic patterns in persistent infection burden among U.S. adults. J Gerontol Ser A Biol Sci Med Sci. 2009;64(2):272–9. doi:10.1093/gerona/gln012.CrossRef Zajacova A, Dowd JB, Aiello AE. Socioeconomic and race/ethnic patterns in persistent infection burden among U.S. adults. J Gerontol Ser A Biol Sci Med Sci. 2009;64(2):272–9. doi:10.​1093/​gerona/​gln012.CrossRef
85.
86.
go back to reference Xia P, Ma MF, Wang W. Status of Helicobacter pylori infection among migrant workers in Shijiazhuang, China. Asian Pac J Cancer Prev. 2012;13(4):1167–70.CrossRefPubMed Xia P, Ma MF, Wang W. Status of Helicobacter pylori infection among migrant workers in Shijiazhuang, China. Asian Pac J Cancer Prev. 2012;13(4):1167–70.CrossRefPubMed
87.
go back to reference Zhang DH, Zhou LY, Lin SR, et al. Recent changes in the prevalence of Helicobacter pylori infection among children and adults in high- or low-incidence regions of gastric cancer in China. Chin Med J. 2009;122(15):1759–63.PubMed Zhang DH, Zhou LY, Lin SR, et al. Recent changes in the prevalence of Helicobacter pylori infection among children and adults in high- or low-incidence regions of gastric cancer in China. Chin Med J. 2009;122(15):1759–63.PubMed
88.
go back to reference Chan FK, To KF, Wu JC, 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(9300):9–13. doi:10.1016/S0140-6736(02)07272-0.CrossRefPubMed Chan FK, To KF, Wu JC, 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(9300):9–13. doi:10.​1016/​S0140-6736(02)07272-0.CrossRefPubMed
90.
91.
go back to reference Bianchi Porro G, Parente F, Imbesi V, Montrone F, Caruso I. Role of Helicobacter pylori in ulcer healing and recurrence of gastric and duodenal ulcers in longterm NSAID users. Response to omeprazole dual therapy. Gut. 1996;39(1):22–6.CrossRefPubMedCentralPubMed Bianchi Porro G, Parente F, Imbesi V, Montrone F, Caruso I. Role of Helicobacter pylori in ulcer healing and recurrence of gastric and duodenal ulcers in longterm NSAID users. Response to omeprazole dual therapy. Gut. 1996;39(1):22–6.CrossRefPubMedCentralPubMed
93.
go back to reference Hawkey CJ, Tulassay Z, Szczepanski L, et al. Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter eradication for lesion prevention. Lancet. 1998;352(9133):1016–21. doi:10.1016/S0140-6736(98)04206-8.CrossRefPubMed Hawkey CJ, Tulassay Z, Szczepanski L, et al. Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs study. Helicobacter eradication for lesion prevention. Lancet. 1998;352(9133):1016–21. doi:10.​1016/​S0140-6736(98)04206-8.CrossRefPubMed
94.
go back to reference Roderick P, Davies R, Raftery J, et al. The cost-effectiveness of screening for Helicobacter pylori to reduce mortality and morbidity from gastric cancer and peptic ulcer disease: a discrete-event simulation model. Health Technol Assess. 2003;7(6):1–86. doi:10.3310/hta7060.CrossRefPubMed Roderick P, Davies R, Raftery J, et al. The cost-effectiveness of screening for Helicobacter pylori to reduce mortality and morbidity from gastric cancer and peptic ulcer disease: a discrete-event simulation model. Health Technol Assess. 2003;7(6):1–86. doi:10.​3310/​hta7060.CrossRefPubMed
95.
96.
Metadata
Title
Prophylactic use of aspirin: systematic review of harms and approaches to mitigation in the general population
Authors
Mangesh A. Thorat
Jack Cuzick
Publication date
01-01-2015
Publisher
Springer Netherlands
Published in
European Journal of Epidemiology / Issue 1/2015
Print ISSN: 0393-2990
Electronic ISSN: 1573-7284
DOI
https://doi.org/10.1007/s10654-014-9971-7

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