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Is There Enough Evidence for Aspirin in High-Risk Groups?

  • Prevention and Early Detection (N Arber, Section Editor)
  • Published:
Current Colorectal Cancer Reports

Abstract

There is convincing evidence of a reduction in vascular disease by aspirin, and highly persuasive evidence of a reduction in cancer, in particular colorectal cancer. Aspirin also increases the risk of gastrointestinal and cerebral bleeding. However, overviews of randomised trial data suggests that gastrointestinal bleeding attributable to aspirin is not the most serious, because there is no evidence of any increase in deaths from bleeding. The involvement of inadequately treated hypertension in cerebral bleeding attributable to aspirin is uncertain. Aspirin is widely approved for vascular risk reduction but no regulatory body has yet approved its use for reduction of cancer risk. Nevertheless, the risk–benefit balance of aspirin should be evaluated in relation to both vascular disease and cancer reduction together. Aspirin prophylaxis would seem to be of particular value as a complement to colorectal cancer screening.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ahmedin Jemal A, Ward E, Hao Y, Thun M. Trends in the leading causes of death in the United States, 1970–2002. J Am Med Ass. 2005;294(10):1255–9.

    Article  Google Scholar 

  2. •• Arber N. Cyclooxygenase-2 inhibition in colorectal cancer prevention. Cancer Epidemiol Biomarkers Prev. 2008;17(8):1852–7. Gives an excellent account of the biological mechanisms involved.

    Article  PubMed  CAS  Google Scholar 

  3. Duncan RE, El-Sohemy A, Archer MC. Statins and cancer. Epidemiology. 2007;18(4):520.

    Article  PubMed  Google Scholar 

  4. Vinogradova Y, Hippisley-Cox J, Coupland C, Logan RF. Risk of colorectal cancer in patients prescribed statins, nonsteroidal anti-inflammatory drugs, and cyclooxygenase-2 inhibitors: nested case–control study. Gastroenterology. 2007;133(2):393–402.

    Article  PubMed  Google Scholar 

  5. Dale KM, Coleman CI, Henyan NH, KLluger J, White M. Statins and cancer risk: a meta-analysis. J Am Med Ass. 2006;295(1):74–80.

    Article  CAS  Google Scholar 

  6. McKee RR. Choosing health? First choose your philosophy. Lancet. 2005;365(9457):369–71.

    PubMed  Google Scholar 

  7. Lenaghan J, New B, Mitchell E. Setting priorities: is there a role for Citizens’ juries? Brit Med J. 1006;312(7046):1591–3.

    Article  Google Scholar 

  8. • Elwood PC, Longley M. My health—whose responsibility: a jury decides. J Epidemiol Community Health. 2002;64(9):761–4. An attempt to obtain informed opinions from representative members of the general public.

    Article  Google Scholar 

  9. Coulter A, Entwistle, Gilbert D. Sharing decisions with patients: is the information good enough? Brit Med J. 1999;318(7179):318.

    Article  PubMed  CAS  Google Scholar 

  10. Hennekens CH, Buring JE, Sandercock P, et al. Aspirin and other antiplatelet agents in the secondary and primary prevention of cardiovascular disease. Circulation. 1989;80(4):749–56.

    Article  PubMed  CAS  Google Scholar 

  11. Antithrombotic Trialists’ Collaboration. Collective meta-analysis of randomised trial of antiplatelet therapy for prevention of death, myocardial infarction and stroke in high risk patients. Brit Med J. 2002;324(7329):71–86.

    Article  Google Scholar 

  12. 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.

    Article  PubMed  Google Scholar 

  13. Raju NMC, Magdalana Sobieraj-Teague MBBS, et al. Effect of aspirin on mortality in the primary prevention of cardiovascular disease. Am J Med. 2011;124(7):621–9.

    Article  PubMed  CAS  Google Scholar 

  14. Kurth T. Aspirin and cancer prevention. Brit Med J. 2012;344:e2480.

    Article  PubMed  Google Scholar 

  15. Chan AT, Cook NR. Are we ready to recommend aspirin for cancer prevention? Lancet. 2012;379(9826):1569–71.

    Article  PubMed  Google Scholar 

  16. Rothwell PM, Fowkes FGR, Belch JFF, et al. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet. 2011;377(9759):31–41.

    Article  PubMed  CAS  Google Scholar 

  17. Kent DM, Shah ND. Personalising evidence-based primary prevention with aspirin: individualised risks and patient preference. Circ Cardiovasc Qual Outcomes. 2011;4(3):260–2.

    Article  PubMed  Google Scholar 

  18. Bosetti C, Gallus S, La Vecchia C. Aspirin and cancer risk: an update to 2001. Eur J Cancer Prev. 2002;11(6):535–42.

    Article  PubMed  CAS  Google Scholar 

  19. Elwood PC, Gallacher AM, Duthie GG, et al. Aspirin, salicylates and cancer. Lancet. 2009;373(9671):1301–9.

    Article  PubMed  CAS  Google Scholar 

  20. Avivi D, Moshkowitz M, Detering E, Arber N. The role of low-dose aspirin in the prevention of colorectal cancer. Expert Opin Ther Targets. 2012;16 Suppl 1:551–62.

    Google Scholar 

  21. Algra AM, Rothwell PM. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet. 2012;13(5):518–27.

    Article  CAS  Google Scholar 

  22. •• Rothwell PM, Wilson M, Elwin C-E, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. Lancet. 2010;376(9754):741–50. The first of a series of long-term follow-up studies of randomised trials to test aspirin prophylaxis in cancer.

    Article  Google Scholar 

  23. Rothwell PM, Price JF, Fowkes FGR, 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 trials. Lancet. 2012;379(9826):1602–12.

    Article  PubMed  CAS  Google Scholar 

  24. Rothwell PM, Wilson M, Price JF, et al. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826):1591–601.

    Article  PubMed  CAS  Google Scholar 

  25. •• Burn J, Gerdes A-M, Macrae F, et al. Long-term effect of aspirin on cancer in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised trial. Lancet. 2010;377(9809):2081–7. An ad-hoc randomised trial of aspirin in the prevention of cancer for patients at very high risk of colorectal cancer.

    Google Scholar 

  26. Mills EJ, Wu P, Alberton M, et al. Low-dose aspirin and cancer mortality: a meta-analysis of randomised trials. Am J Med. 2012;125:560–7.

    Article  PubMed  CAS  Google Scholar 

  27. Jacobs EJ, Newton CC, Gaostur SM, et al. Daily aspirin use and cancer mortality in a large US cohort. J Nat Cancer Inst. 2012;104(16):1208–17.

    Article  PubMed  CAS  Google Scholar 

  28. • Gasic GJ, Gasic TB, Murphy S. Anti-metastatic effect of aspirin. Lancet. 1972;300(7783):932–33. One of the earliest reports which gave evidence on aspirin and cancer.

    Article  Google Scholar 

  29. Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. J Am Med Ass. 2009;302(6):649–59.

    Article  CAS  Google Scholar 

  30. Holmes MD, Chen WY, Li L, Hertzmark E, Spiegleman D, Hankinson SE. Aspirin intake and survival after breast cancer. J Clin Oncology. 2010;28(9):1467–72.

    Article  CAS  Google Scholar 

  31. Liu J-F, Jamieson GG, Wu T-C, Zhu G-J, Drew PA. A preliminary study on the postoperative survival of patients given aspirin after resection for squamous cell carcinoma of the esophagus or adenocarcinoma of the cardia. Ann Surg Oncology. 2009;16(5):1397–402.

    Article  Google Scholar 

  32. Fontaine E, McShane J, Page R, et al. Aspirin and non-small cell lung cancer resections: effect on long-term survival. Eur J Cardiothorac Surg. 2010;38(1):21–6.

    Article  PubMed  Google Scholar 

  33. Liao X, Lochhead P, Nishihara R, et al. Aspirin use, tumor PIK3CA mutation and colorectal-cancer survival. New Rng J Med. 2012;367(17):1596–606.

    Article  CAS  Google Scholar 

  34. Griffin MR, Ray WA, Schaffner W. Non-steroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons. Ann Int Med. 1988;109(5):359–63.

    PubMed  CAS  Google Scholar 

  35. Tramer MR, Moore RA, Reynolds DJM, McQuay HJ. Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use. Pain. 2000;85:169–82.

    Article  PubMed  CAS  Google Scholar 

  36. Patrono C, Garcia Rodriguez LA, Landolfi R, et al. Low-dose aspirin for the prevention of atherosclerosis. N Eng J Med. 2005;353(22):2373–83.

    Article  CAS  Google Scholar 

  37. McQuaid KR, Laine L. Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomised controlled trials. Am J Med. 2006;119(8):624–38. A thorough evaluation of the GI bleeding risks of aspirin.

    Article  PubMed  CAS  Google Scholar 

  38. de Berardis G, Lucisane G, D’ettorre A, et al. Association of aspirin use with major bleeding in patients with and without diabetes. J Am Med Ass. 2012;307(21):2786–94.

    Google Scholar 

  39. Morgan G. Aspirin for the primary prevention of vascular events? Public Health. 2009;123(12):787–8.

    Article  PubMed  CAS  Google Scholar 

  40. Lanas A, Perez-Aisa MA, Feu F, et al. A nationwide study of mortality associated with hospital admission due to severe GI events and those associated with NSAID use. Am J Gastroenterology. 2005;100(8):1685–93.

    Article  CAS  Google Scholar 

  41. Abraham NS. National mortality following upper gastrointestinal or cardiovascular events in older veterans with recent NSAID drug use. Aliment Pharmacol Ther. 2008;28(1):97–106.

    Article  PubMed  CAS  Google Scholar 

  42. Garcia Rodriguez LA, Hermandez S, de Abajo J. Association between aspirin and upper gastrointestinal complications: systematic review of epidemiologic studies. Br J Clin Pharmacol. 2001;52(5):563–71.

    Article  PubMed  CAS  Google Scholar 

  43. •• Biondi-Zoccail GGL, Loyrionte M, Agostoni P, et al. Systematic review and meta-analysis on the hazards of discontinuing or not adhering to aspirin among 50,279 patients at risk for coronary artery disease. Eur Heart J. 2006;27(22):2667–74. An overview of rebound in vascular risk after aspirin is withdrawn.

    Article  Google Scholar 

  44. •• Sung JJ, Ching JY, Wu LC, et al. Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomised trial. Ann Int Med. 2010;152(1):1–9. A courageous test of recommencing aspirin by subjects who had had GI bleeding.

    PubMed  Google Scholar 

  45. Gorlick PB, Weisman SM. Risk of haemorrhagic stroke with aspirin use: an update. Stroke. 2005;36(8):1801–7.

    Article  Google Scholar 

  46. 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) trial. HOT study group. Lancet. 1998;351(9118):1755–62.

    Article  PubMed  CAS  Google Scholar 

  47. Lip GYH, Felmeden DC, Dwivedi G. Antiplatelet agents and anticoagulants for hypertension. Cochrane Database Syst Rev. 2011;(12):CD003186.

  48. Joint British Societies’ Guidelines on Prevention of Cardiovascular Disease in Clinical Practice. Heart. 2005;91(Suppl 5):v1–52.

    Google Scholar 

  49. O’Brien JR. Effect of salicylates on human platelets. Lancet. 1968;1(7557):1431.

    Article  PubMed  Google Scholar 

  50. Sostres C, Lanas A. Gastrointestinal effects of aspirin. Nat Rev Gastroenterol Hepatol. 2011;8(7):385–94.

    Article  PubMed  CAS  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.

    Article  PubMed  Google Scholar 

  52. EDTRS Investigators. Aspirin effects on mortality and morbidity in patients with diabetes mellitus. J Am Med Assoc. 1992;268(10):1292–300.

    Article  Google Scholar 

  53. Rocca B, Santilli F, Pitocco D, et al. The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes. J Thromb Haemost. 2012;10(7):1220–30.

    Article  PubMed  CAS  Google Scholar 

  54. Chan AT, Manson JE, Feskanich D, et al. Long-term aspirin use and mortality in women. Arch Intern Med. 2007;167(6):562–72.

    Article  PubMed  Google Scholar 

  55. Herderschee D, Hijdra A, Algra A, et al. Silent stroke in patients with transient ischaemic attack or minor ischaemic stroke. The Dutch TIA Trial Study Group. Stroke. 1992;23(9):1220–4.

    Article  PubMed  CAS  Google Scholar 

  56. Ebrahim S, Casas JP. Statins for all by the age of 50 years? Lancet. 2012;380(9841):545–7.

    Article  PubMed  Google Scholar 

  57. Amarenco P, Bogousslavsky J, Callahan 3rd A, et al. High dose atorvastatin after stroke or transient ischaemic attack. N Engl J Med. 2006;355(6):549–59.

    Article  PubMed  CAS  Google Scholar 

  58. Atkin WS, Edwards R, Ines K-H, et al. Once only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010;375(9726):1624–33.

    Article  PubMed  Google Scholar 

  59. •• Logan RFA, Patnick J, Nickerson C et al. Outcomes of the bowel cancer screening programme (BCSP) in England after the first 1 million tests. Gut 2012 Oct 8. A critical evaluation of the risks, the benefits, and the incidental findings in colorectal screening.

  60. Liberman D. Progress and challenges in colorectal cancer screening and surveillance. Gastroenterology. 2010;138(6):2115–26.

    Article  Google Scholar 

  61. Sing H, Penfold RB, de Coster C, et al. Colonoscopy and its complications across a Canadian regional health authority. Gastrointest Endosc. 2009;69(3Pt2):665–71.

    Article  Google Scholar 

  62. Warren JL, Klabunde CN, Mariotto AB, et al. Adverse effects after outpatient colonoscopy in the Medicare population. Ann Intern Med. 2009;150(12):849–57. W152.

    PubMed  Google Scholar 

  63. Rutter CM, Johnson E, Miglioretti DL, et al. Adverse events after screening and follow-up colonoscopy. Cancer Causes Control. 2012;23(2):289–96.

    Article  PubMed  Google Scholar 

  64. Hassan C, Rex DK, Cooper GS, et al. Primary prevention of colorectal cancer with low-dose aspirin in combination with endoscopy: a cost-effective analysis. Gut. 2012;61(8):1172–9.

    Article  PubMed  Google Scholar 

  65. Brenner H, Tao S, Haug U. Low-dose aspirin use and performance of immunochemical fecal occult blood tests. J Am Med Ass. 2010;304(22):2513–20.

    Article  CAS  Google Scholar 

  66. Yuhara H, Steinmaus C, Cohen SE, et al. Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer? Am J Gastroenterol. 2011;106(11):1911–21.

    Article  PubMed  Google Scholar 

  67. Elwood P, Morgan G, Brown G, Pickering J. Aspirin for everyone over 50? Brit Med J. 2005;330975050:1440–1.

    Article  Google Scholar 

  68. Vandvick PO, Lincoff M, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2 Suppl):e637S–685.

    Article  Google Scholar 

  69. Baigent C. Aspirin for all over 50? Against. Brit Med J. 2005;330(7505):1442–3.

    Article  PubMed  Google Scholar 

  70. Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastrenterol. 2006;101(2):385–98.

    Article  Google Scholar 

  71. Frazier AL, Colditz GA, Fuchs CS, et al. Cost effectiveness of screening for colorectal cancer in the general population. J Am Med Ass. 2000;284(15):1954–61.

    Article  CAS  Google Scholar 

  72. Williams AR, Balasooriya BA, Day DW. Polyps and cancer of the large bowel: a necropsy study in Liverpool. Gut. 1982;23(10):835–42.

    Article  PubMed  CAS  Google Scholar 

  73. Driver JA, Gazino JM, Gelber RP, et al. Development of a risk score for colorectal cancer in men. Am J Med. 2007;120(3):257–63.

    Article  PubMed  Google Scholar 

  74. Yeoh K-G, Ho Y-Y, Chiu H-M, et al. The Asia–Pacific colorectal screening score: a validated tool that stratifies risk for colorectal advanced neoplasi in asymptomatic Asian subjects. Gut. 2011;60(9):1236–41.

    Article  PubMed  Google Scholar 

  75. Hennekens CH, Baigent C. Aspirin in primary prevention – good news and bad news. Nat Rev Cardiol. 2012;58(1):303–4.

    CAS  Google Scholar 

  76. Elwood PC, White J, Fone D, et al. Aspirin taking in the community: a cross-sectional survey. Brit J Cardiol. 2012;18(5/6):238–0.

    Google Scholar 

  77. Ajani UA, Ford ES, Greenland KJ. Aspirin use among US adults: behavioural risk factor surveillance system. Am J Prev Med. 2006;30(1):74–7.

    Article  PubMed  Google Scholar 

  78. Blatt 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. Circulation. 2008;118(18):1894–909.

    Article  Google Scholar 

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  1. Cochrane Institute of Primary Care and Public Health, Cardiff University, University Hospital of Wales, Cardiff, CF14 4XN, UK

    Peter C. Elwood & Mohammed Mustafa

  2. Cochrane Institute of Primary Care and Public Health, Cardiff University, Cardiff, CF14 5YS, UK

    Maribel Almonte

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  1. Peter C. Elwood
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  2. Maribel Almonte
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Correspondence to Peter C. Elwood.

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Elwood, P.C., Almonte, M. & Mustafa, M. Is There Enough Evidence for Aspirin in High-Risk Groups?. Curr Colorectal Cancer Rep 9, 9–16 (2013). https://doi.org/10.1007/s11888-012-0149-y

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