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

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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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Abbreviations

ACS:

American Cancer Society

ATT:

Antithrombotic Trialists

BDT:

British Doctors’ Trial

BHF:

British Heart Foundation

CRUK:

Cancer Research UK

CVD:

Cardiovascular disease

HPFS:

Health Professionals Follow-up Study

HTA:

Health Technology Assessment

GI:

Gastrointestinal

ISCaP:

International Society of Cancer Prevention

LGIB:

Lower gastrointestinal bleeding

NANSAIDs:

Non-aspirin NSAIDs

NHS:

Nurses’ Health Study

ONS:

Office of National Statistics

PHS:

Physicians’ Health Study

SAH:

Sub-arachnoid haemorrhage

UGIB:

Upper gastrointestinal bleeding

UGIC:

Upper gastrointestinal complications

USPSTF:

U.S. Preventive Services Task Force

WHS:

Women’s Health Study

1,000-PY:

1,000 Person years

References

  1. Mahdi JG, Mahdi AJ, Mahdi AJ, Bowen ID. The historical analysis of aspirin discovery, its relation to the willow tree and antiproliferative and anticancer potential. Cell Prolif. 2006;39(2):147–55. doi:10.1111/j.1365-2184.2006.00377.x.

    Article  CAS  PubMed  Google Scholar 

  2. Sneader W. The discovery of aspirin: a reappraisal. BMJ. 2000;321(7276):1591–4. doi:10.1136/bmj.321.7276.1591.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Miner J, Hoffhines A. The discovery of aspirin’s antithrombotic effects. Tex Heart Inst J. 2007;34(2):179–86.

    PubMed Central  PubMed  Google Scholar 

  4. Cuzick J, Otto F, Baron JA, et al. Aspirin and non-steroidal anti-inflammatory drugs for cancer prevention: an international consensus statement. Lancet Oncol. 2009;10(5):501–7. doi:10.1016/S1470-2045(09)70035-X.

    Article  CAS  PubMed  Google Scholar 

  5. Thorat MA, Cuzick J. Role of aspirin in cancer prevention. Curr Oncol Rep. 2013;15(6):533–40. doi:10.1007/s11912-013-0351-3.

    Article  CAS  PubMed  Google Scholar 

  6. Hunter DJ, Reddy KS. Noncommunicable diseases. N Engl J Med. 2013;369(14):1336–43. doi:10.1056/NEJMra1109345.

    Article  CAS  PubMed  Google Scholar 

  7. Patrono C, Garcia Rodriguez LA, Landolfi R, Baigent C. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005;353(22):2373–83. doi:10.1056/NEJMra052717.

    Article  CAS  PubMed  Google Scholar 

  8. Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med. 2002;347(15):1175–86. doi:10.1056/NEJMra020542.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Google Scholar 

  10. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339:b2535. doi:10.1136/bmj.b2535.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Office for National Statistics. Mortality statistics: deaths registered in 2008. National Statistics London; 2009.

  12. Cai S, Garcia Rodriguez LA, Masso-Gonzalez EL, Hernandez-Diaz S. Uncomplicated peptic ulcer in the UK: trends from 1997 to 2005. Aliment Pharmacol Ther. 2009;30(10):1039–48. doi:10.1111/j.1365-2036.2009.04131.x.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  PubMed  Google Scholar 

  14. Hippisley-Cox J, Coupland C, Logan R. Risk of adverse gastrointestinal outcomes in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ. 2005;331(7528):1310–6. doi:10.1136/bmj.331.7528.1310.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. Button LA, Roberts SE, Evans PA, et al. Hospitalized incidence and case fatality for upper gastrointestinal bleeding from 1999 to 2007: a record linkage study. Aliment Pharmacol Ther. 2010;33(1):64–76. doi:10.1111/j.1365-2036.2010.04495.x.

    Article  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. Kang JY, Elders A, Majeed A, Maxwell JD, Bardhan KD. Recent trends in hospital admissions and mortality rates for peptic ulcer in Scotland 1982–2002. Aliment Pharmacol Ther. 2006;24(1):65–79. doi:10.1111/j.1365-2036.2006.02960.x.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  PubMed  Google Scholar 

  21. 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.

    CAS  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. 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.

    Article  PubMed  Google Scholar 

  24. Mose H, Larsen M, Riis A, Johnsen SP, Thomsen RW, Sorensen HT. Thirty-day mortality after peptic ulcer bleeding in hospitalized patients receiving low-dose aspirin at time of admission. Am J Geriatr Pharmacother. 2006;4(3):244–50. doi:10.1016/j.amjopharm.2006.09.006.

    Article  PubMed  Google Scholar 

  25. Straube S, Tramer MR, Moore RA, Derry S, McQuay HJ. Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. BMC Gastroenterol. 2009;9:41. doi:10.1186/1471-230X-9-41.

    Article  PubMed Central  PubMed  Google Scholar 

  26. 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 antiinflammatory drug use. Am J Gastroenterol. 2005;100(8):1685–93. doi:10.1111/j.1572-0241.2005.41833.x.

    Article  CAS  PubMed  Google Scholar 

  27. Berger JS, Lala A, Krantz MJ, Baker GS, Hiatt WR. Aspirin for the prevention of cardiovascular events in patients without clinical cardiovascular disease: a meta-analysis of randomized trials. Am Heart J. 2011;162(1):115–24. doi:10.1016/j.ahj.2011.04.006.

    Article  CAS  PubMed  Google Scholar 

  28. Derry S, Loke YK. Risk of gastrointestinal haemorrhage with long term use of aspirin: meta-analysis. BMJ. 2000;321(7270):1183–7. doi:10.1136/bmj.321.7270.1183.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Hart RG, Halperin JL, McBride R, Benavente O, Man-Son-Hing M, Kronmal RA. Aspirin for the primary prevention of stroke and other major vascular events: meta-analysis and hypotheses. Arch Neurol. 2000;57(3):326–32. doi:10.1001/archneur.57.3.326.

    Article  CAS  PubMed  Google Scholar 

  30. Lanas A, Wu P, Medin J, Mills EJ. Low doses of acetylsalicylic acid increase risk of gastrointestinal bleeding in a meta-analysis. Clin Gastroenterol Hepatol. 2011;9(9):762–8. doi:10.1016/j.cgh.2011.05.020.

    Article  CAS  PubMed  Google Scholar 

  31. McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med. 2006;119(8):624–38. doi:10.1016/j.amjmed.2005.10.039.

    Article  CAS  PubMed  Google Scholar 

  32. Raju N, Sobieraj-Teague M, Hirsh J, O’Donnell M, Eikelboom J. Effect of aspirin on mortality in the primary prevention of cardiovascular disease. Am J Med. 2011;124(7):621–9. doi:10.1016/j.amjmed.2011.01.018.

    Article  CAS  PubMed  Google Scholar 

  33. Sanmuganathan PS, Ghahramani P, Jackson PR, Wallis EJ, Ramsay LE. Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials. Heart. 2001;85(3):265–71. doi:10.1136/heart.85.3.265.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Serebruany VL, Steinhubl SR, Berger PB, et al. Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials. Am J Cardiol. 2005;95(10):1218–22. doi:10.1016/j.amjcard.2005.01.049.

    Article  CAS  PubMed  Google Scholar 

  35. Seshasai SR, Wijesuriya S, Sivakumaran R, et al. Effect of aspirin on vascular and nonvascular outcomes: meta-analysis of randomized controlled trials. Arch Intern Med. 2012;172(3):209–16. doi:10.1001/archinternmed.2011.628.

    Article  CAS  PubMed  Google Scholar 

  36. Connolly BJ, Pearce LA, Kurth T, Kase CS, Hart RG. Aspirin therapy and risk of subdural hematoma: meta-analysis of randomized clinical trials. J Stroke Cerebrovasc Dis. 2013;22(4):444–8. doi:10.1016/j.jstrokecerebrovasdis.2013.01.007.

    Article  PubMed  Google Scholar 

  37. Huang ES, Strate LL, Ho WW, Lee SS, Chan AT. Long-term use of aspirin and the risk of gastrointestinal bleeding. Am J Med. 2011;124(5):426–33. doi:10.1016/j.amjmed.2010.12.022.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. 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.

    Article  CAS  PubMed  Google Scholar 

  39. Garcia Rodriguez LA, Lin KJ, Hernandez-Diaz S, Johansson S. Risk of upper gastrointestinal bleeding with low-dose acetylsalicylic acid alone and in combination with clopidogrel and other medications. Circulation. 2011;123(10):1108–15. doi:10.1161/CIRCULATIONAHA.110.973008.

    Article  CAS  PubMed  Google Scholar 

  40. Sakamoto C, Sugano K, Ota S, et al. Case-control study on the association of upper gastrointestinal bleeding and nonsteroidal anti-inflammatory drugs in Japan. Eur J Clin Pharmacol. 2006;62(9):765–72. doi:10.1007/s00228-006-0171-6.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Ibanez L, Vidal X, Vendrell L, Moretti U, Laporte JR, Spanish-Italian Collaborative Group for the Epidemiology of Gastrointestinal B. Upper gastrointestinal bleeding associated with antiplatelet drugs. Aliment Pharmacol Ther. 2006;23(2):235–42. doi:10.1111/j.1365-2036.2006.02759.x.

    Article  CAS  PubMed  Google Scholar 

  43. 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.

    Article  CAS  PubMed  Google Scholar 

  44. de Abajo FJ, Garcia Rodriguez LA. Risk of upper gastrointestinal bleeding and perforation associated with low-dose aspirin as plain and enteric-coated formulations. BMC Clin Pharmacol. 2001;1:1. doi:10.1186/1472-6904-1-1.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Lanas A, Bajador E, Serrano P, et al. Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med. 2000;343(12):834–9. doi:10.1056/NEJM200009213431202.

    Article  CAS  PubMed  Google Scholar 

  46. 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.

    Article  CAS  PubMed  Google Scholar 

  47. Schmidt M, Johansen MB, Lash TL, Christiansen CF, Christensen S, Sorensen HT. Antiplatelet drugs and risk of subarachnoid hemorrhage: a population-based case-control study. J Thromb Haemost. 2010;8(7):1468–74. doi:10.1111/j.1538-7836.2010.03856.x.

    Article  CAS  PubMed  Google Scholar 

  48. De Berardis G, Lucisano G, D’Ettorre A, et al. Association of aspirin use with major bleeding in patients with and without diabetes. JAMA. 2012;307(21):2286–94. doi:10.1001/jama.2012.5034.

    Article  PubMed  Google Scholar 

  49. Huang ES, Strate LL, Ho WW, Lee SS, Chan AT. A prospective study of aspirin use and the risk of gastrointestinal bleeding in men. PLoS ONE. 2010;5(12):e15721. doi:10.1371/journal.pone.0015721.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Sorensen HT, Mellemkjaer L, Blot WJ, et al. Risk of upper gastrointestinal bleeding associated with use of low-dose aspirin. Am J Gastroenterol. 2000;95(9):2218–24. doi:10.1111/j.1572-0241.2000.02248.x.

    Article  CAS  PubMed  Google Scholar 

  51. 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.

    Article  PubMed Central  PubMed  Google Scholar 

  52. de Gaetano G. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative group of the primary prevention project. Lancet. 2001;357(9250):89–95. doi:10.1016/S0140-6736(00)03539-X.

    Article  PubMed  Google Scholar 

  53. 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.

    Article  CAS  PubMed  Google Scholar 

  54. 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.

    Article  Google Scholar 

  55. 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.

    Article  CAS  PubMed  Google Scholar 

  56. Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134–41. doi:10.1001/jama.2008.623.

    Article  CAS  PubMed  Google Scholar 

  57. 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.

    Article  CAS  Google Scholar 

  58. Ridker PM, Cook NR, Lee IM, et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med. 2005;352(13):1293–304. doi:10.1056/NEJMoa050613.

    Article  CAS  PubMed  Google Scholar 

  59. 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(3):129–35. doi:10.1056/NEJM198907203210301.

    Article  Google Scholar 

  60. Vyse AJ, Gay NJ, Hesketh LM, et al. The burden of Helicobacter pylori infection in England and Wales. Epidemiol Infect. 2002;128(3):411–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  61. 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.

    CAS  Google Scholar 

  62. Jackson L, Britton J, Lewis SA, et al. A population-based epidemiologic study of Helicobacter pylori infection and its association with systemic inflammation. Helicobacter. 2009;14(5):108–13. doi:10.1111/j.1523-5378.2009.00711.x.

    Article  PubMed  Google Scholar 

  63. 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. doi:10.1016/S0140-6736(02)07273-2.

    Article  CAS  PubMed  Google Scholar 

  64. Papatheodoridis GV, Sougioultzis S, Archimandritis AJ. Effects of Helicobacter pylori and nonsteroidal anti-inflammatory drugs on peptic ulcer disease: a systematic review. Clin Gastroenterol Hepatol. 2006;4(2):130–42. doi:10.1016/j.cgh.2005.10.006.

    Article  PubMed  Google Scholar 

  65. Fletcher EH, Johnston DE, Fisher CR, Koerner RJ, Newton JL, Gray CS. Systematic review: Helicobacter pylori and the risk of upper gastrointestinal bleeding risk in patients taking aspirin. Aliment Pharmacol Ther. 2010;32(7):831–9. doi:10.1111/j.1365-2036.2010.04415.x.

    Article  CAS  PubMed  Google Scholar 

  66. Mathers C, Fat DM, Boerma JT, World Health Organization. The global burden of disease: 2004 update. Geneva: World Health Organization; 2008.

    Google Scholar 

  67. 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.

    Article  CAS  PubMed  Google Scholar 

  68. Garcia Rodriguez LA, Hernandez-Diaz S, de Abajo FJ. Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies. Br J Clin Pharmacol. 2001;52(5):563–71. doi:10.1046/j.0306-5251.2001.01476.x.

    Article  CAS  PubMed  Google Scholar 

  69. Graham DY, Smith JL, Spjut HJ, Torres E. Gastric adaptation. Studies in humans during continuous aspirin administration. Gastroenterology. 1988;95(2):327–33.

    CAS  PubMed  Google Scholar 

  70. Graham DY, Smith JL, Dobbs SM. Gastric adaptation occurs with aspirin administration in man. Dig Dis Sci. 1983;28(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  71. 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.

    Article  CAS  PubMed  Google Scholar 

  72. Watanabe T, Sugimori S, Kameda N, et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol: a pilot study. Clin Gastroenterol Hepatol. 2008;6(11):1279–82. doi:10.1016/j.cgh.2008.06.021.

    Article  PubMed  Google Scholar 

  73. 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.

    Article  CAS  PubMed  Google Scholar 

  74. 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.

    Article  CAS  Google Scholar 

  75. Matsumura T, Arai M, Sazuka S, et al. Negative capsule endoscopy for obscure gastrointestinal bleeding is closely associated with the use of low-dose aspirin. Scand J Gastroenterol. 2011;46(5):621–6. doi:10.3109/00365521.2010.545833.

    Article  CAS  PubMed  Google Scholar 

  76. 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.

    Article  CAS  PubMed  Google Scholar 

  77. Rahme E, Roussy JP, Woolcott J, Nedjar H, Barkun A. Mortality and readmission rates after hospitalization for upper and lower gastrointestinal events in Quebec, Canada. J Clin Gastroenterol. 2013;47(7):586–92. doi:10.1097/MCG.0b013e318282a1d7.

    Article  CAS  PubMed  Google Scholar 

  78. Hernandez-Diaz S, Garcia Rodriguez LA. Cardioprotective aspirin users and their excess risk of upper gastrointestinal complications. BMC Med. 2006;4:22. doi:10.1186/1741-7015-4-22.

    Article  PubMed Central  PubMed  Google Scholar 

  79. U.S. Preventive Services Task Force (USPSTF). Aspirin for the prevention of cardiovascular disease: U.S. Preventive Services task force recommendation statement. Ann Intern Med. 2009;150(6):396–404. doi:10.7326/0003-4819-150-6-200903170-00008.

    Article  Google Scholar 

  80. Wolff T, Miller T, Ko S. Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. preventive services task force. Ann Intern Med. 2009;150(6):405–10. doi:10.7326/0003-4819-150-6-200903170-00009.

    Article  PubMed  Google Scholar 

  81. 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.

    Google Scholar 

  82. 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.

    Article  Google Scholar 

  83. Gao L, Weck MN, Stegmaier C, Rothenbacher D, Brenner H. Alcohol consumption, serum gamma-glutamyltransferase, and Helicobacter pylori infection in a population-based study among 9733 older adults. Ann Epidemiol. 2010;20(2):122–8. doi:10.1016/j.annepidem.2009.11.009.

    Article  PubMed  Google Scholar 

  84. Schottker B, Adamu MA, Weck MN, Muller H, Brenner H. Helicobacter pylori infection, chronic atrophic gastritis and major cardiovascular events: a population-based cohort study. Atherosclerosis. 2012;220(2):569–74. doi:10.1016/j.atherosclerosis.2011.11.029.

    Article  PubMed  Google Scholar 

  85. Bode G, Rothenbacher D, Brenner H. Helicobacter pylori colonization and diarrhoeal illness: results of a population-based cross-sectional study in adults. Eur J Epidemiol. 2001;17(9):823–7. doi:10.1023/A:1015618112695.

    Article  CAS  PubMed  Google Scholar 

  86. 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.

    Article  PubMed  Google Scholar 

  87. 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  Google Scholar 

  88. 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.

    Article  CAS  PubMed  Google Scholar 

  89. Chan FK, Sung JJ, Chung SC, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet. 1997;350(9083):975–9. doi:10.1016/S0140-6736(97)04523-6.

    Article  CAS  PubMed  Google Scholar 

  90. 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(13):967–73. doi:10.1056/NEJM200103293441304.

    Article  CAS  PubMed  Google Scholar 

  91. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  92. Chan FK, Sung JJ, Suen R, et al. Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study. Aliment Pharmacol Ther. 1998;12(12):1201–5. doi:10.1046/j.1365-2036.1998.00434.x.

    Article  CAS  PubMed  Google Scholar 

  93. 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.

    Article  CAS  PubMed  Google Scholar 

  94. 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.

    Article  CAS  PubMed  Google Scholar 

  95. Saini SD, Schoenfeld P, Fendrick AM, Scheiman J. Cost-effectiveness of proton pump inhibitor cotherapy in patients taking long-term, low-dose aspirin for secondary cardiovascular prevention. Arch Intern Med. 2008;168(15):1684–90. doi:10.1001/archinte.168.15.1684.

    Article  PubMed  Google Scholar 

  96. Lanas A. Prevention of aspirin-induced gastroduodenal damage: H. pylori infection eradication versus proton pump inhibitors or both. Dig Liver Dis. 2004;36(10):655–7. doi:10.1016/j.dld.2004.06.010.

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Acknowledgments

This study was a part of broader review of prophylactic use of aspirin. The review was sponsored by International Society of Cancer Prevention (ISCaP), Cancer Research UK (CRUK), British Heart Foundation (BHF) and American Cancer Society (ACS) and received funding from CRUK, BHF and ACS. Sponsors and funding sources had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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JC: Member of the Bayer advisory board. MAT: None.

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Authors and Affiliations

  1. Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, EC1M 6BQ, UK

    Mangesh A. Thorat & Jack Cuzick

  2. Division of Surgery and Interventional Science, Whittington Hospital, Magdala Avenue, London, N19 5NF, UK

    Mangesh A. Thorat

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  1. Mangesh A. Thorat
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  2. Jack Cuzick
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Correspondence to Mangesh A. Thorat.

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Thorat, M.A., Cuzick, J. Prophylactic use of aspirin: systematic review of harms and approaches to mitigation in the general population. Eur J Epidemiol 30, 5–18 (2015). https://doi.org/10.1007/s10654-014-9971-7

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  • DOI: https://doi.org/10.1007/s10654-014-9971-7

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