Aspirin is widely used internationally for a variety of indications, with the most prominent one being that of cardiovascular disease. However, aspirin has also been proposed as a treatment option in a diverse range of conditions such as diabetes mellitus, cancer prevention, and obstetrics. In our overview, we critically appraise the current evidence from recent systematic reviews and meta-analyses covering the benefits of aspirin across these conditions. We also look at evidence that some patients may not derive benefit due to the concept of aspirin resistance. Aspirin is also associated with the potential for significant harm, principally from haemorrhagic adverse events. We critically appraise the threat of haemorrhagic complications, and weigh up these risks against that of any potential benefit.
References
[1]
Antiplatelet Trialists’ Collaboration. Collaborative overview of randomised trials of antiplatelet therapy I: prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ？1994, 308, 81–106. 8298418
[2]
Antithromboic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ？2002, 324, 71–86, doi:10.1136/bmj.324.7329.71. 11786451
[3]
Antithromboic Trialists’ Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet？2009, 373, 1849–1860, doi:10.1016/S0140-6736(09)60503-1. 19482214
[4]
US Preventive Services Task Force. Aspirin for the prevention of cardiovascular disease: US Preventive Service Task Force Recommendation Statement. Ann. Intern. Med.？2009, 150, 396–404. 19293072
[5]
Pearson, T.A.; Blair, S.N.; Daniels, S.R.; Eckel, R.H.; Fair, J.M.; Fortmann, S.P.; Franklin, B.A.; Goldstein, L.B.; Greenland, P.; Grundy, S.M.; et al. AHA Guidelines for primary prevention of cardiovascular disease and stroke 2002 update. Circulation？2002, 106, 388–391. 12119259
[6]
JBS 2: Joint British Societies’ guidelines on prevention of cardiovascular disease in clinical practice. Heart？2005, 91 (Suppl. 5), v1–v52, doi:10.1136/hrt.2005.079988. 16365341
[7]
Kuliczkowski, W.; Halawa, B.; Korolko, B.; Mazurek, W. Aspirin resistance in ischemic heart disease. Kariol. Pol.？2005, 62, 14–19.
[8]
Angiolillo, D.J.; Fernandez-Ortiz, A.; Bernardo, E.; Ramirez, D.; Sabate, M.; Jimenez-Quevedo, P.; Hernandez, R.; Moreno, R.; Escaned, J.; Alfonso, F.; Ba？uelos, C.; Costa, M.A.; Bass, T.A.; Macaya, C. Influence of aspirin resistance on platelet function profiles in patients on long-term aspirin and clopidogrel after percutaneous coronary intervention. Am. J. Cardiol.？2006, 97, 38–43, doi:10.1016/j.amjcard.2005.07.106. 16377281
[9]
Hegason, C.M.; Bolin, K.M.; Hoff, J.A.; Winkler, S.R.; Manget, A.; Tortorice, K.L.; Brace, L.D. Development of aspirin resistance in persons with previous ischaemic stroke. Stroke？1994, 25, 2331–2336, doi:10.1161/01.STR.25.12.2331. 7974569
[10]
Kawasaki, T.; Ozeki, Y.; Igawa, T.; Kambayashi, J.-I. Increased platelet sensitivity to collagen in individuals resistant to low dose aspirin. Stroke？2000, 31, 591–596, doi:10.1161/01.STR.31.3.591. 10700490
[11]
Macchi, L.; Christianes, L.; Brabant, S.; Sorel, N.; Allal, J.; Mauco, G.; Brizard, A. Resistance to aspirin is associated with platelet sensitivity to adenosine diphosphate. Thromb. Res.？2002, 107, 45–49, doi:10.1016/S0049-3848(02)00210-4. 12413588
[12]
Zimmerman, N.; Wenk, A.; Kim, U.; Kienzel, P.; Weber, A.A.; Gams, E.; Schror, K.; Hohlfeld, T. Functional and biochemical evaluation of platelet aspirin resistance after coronary artery bypass surgery. Circulation？2003, 108, 542–547, doi:10.1161/01.CIR.0000081770.51929.5A. 12874188
[13]
Krasopoulos, G.; Brister, S.J.; Beattie, W.S.; Elliot, R.F.; Buchanan, M.R. Aspirin “resistance” and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ？2008, 336, 195–198, doi:10.1136/bmj.39430.529549.BE. 18202034
[14]
Patrono, C.; Garcia Rodriguez, L.A.; Landolfi, R.; Baigent, C. Low-dose aspirin for the prevention of atherothrombosis. N. Engl. J. Med.？2005, 353, 2373–2383, doi:10.1056/NEJMra052717. 16319386
[15]
Buchanan, M.R. Biological basis and clinical implications of acetylsalicylic acid resistance. Can. J. Cardiol.？2006, 22, 149–151, doi:10.1016/S0828-282X(06)70255-0. 16485051
[16]
Eikelboon, J.W.; Hirsh, J.; Weitz, J.I.; Johnson, M.; Yi, Q.; Yusef, S. Aspirin-resistant thromboxane biosynthesis and risk of myocardial infarction, stroke or cardiovascular death in patients at high risk for cardiovascular events. Circulation？2002, 105, 1650–1655, doi:10.1161/01.CIR.0000013777.21160.07. 11940542
[17]
Patrono, C. Aspirin resistance: definition, mechanisms and clinical read-outs. J. Thrombo. Haemost.？2003, 1, 1710–1713, doi:10.1046/j.1538-7836.2003.00284.x.
[18]
Hennekens, C.H.; Schor, K.; Weisman, S.; Fitzgerald, G.A. Semantic complexity and aspirin resistance. Circulation？2004, 110, 1706–1708, doi:10.1161/01.CIR.0000142056.69970.DB. 15381661
[19]
Cattaneo, M. Aspirin and clopidogrel: efficacy, safety, and the issues of drug resistance. Arterioscler. Throm. Vasc. Biol.？2004, 24, 1980–1987, doi:10.1161/01.ATV.0000145980.39477.a9.
[20]
Duley, L.; Hendeson-Smart, D.J.; Knight, M.; King, J. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst. Rev.？2003, 1, CD004659.
[21]
Sibai, B.M.; Cartis, S.; Thom, E.; Klebanoff, M.; McNellis, D.; Rocco, L.; Paul, R.H.; Romero, R.; Witter, F.; Rosen, M.; et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. N. Engl. J. Med.？1993, 329, 1213–1218, doi:10.1056/NEJM199310213291701. 8413387
[22]
CLASP (Collaborative Low-dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a randomised trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364 pregnant women. Lancet？1994, 343, 619–629. 7906809
[23]
Golding, J. A randomised trial of low dose aspirin for primipara in pregnancy. Br. J. Obstet. Gynaecol.？1998, 105, 293–299, doi:10.1111/j.1471-0528.1998.tb10089.x. 9532989
[24]
Rotchell, Y.E.; Cruikshank, J.K.; Gay, M.P.; Griffiths, J.; Stewart, A.; Farrell, B.; Ayers, S.; Hennis, A.; Grant, A.; Duley, L.; Collins, R. Barbados Low Dose Aspirin Study in Pregnancy (BLASP): a randomised trial for the prevention of pre-eclampsia and its complications. Br. J. Obstet. Gynaecol.？1998, 105, 286–292, doi:10.1111/j.1471-0528.1998.tb10088.x. 9532988
[25]
Cartitis, S.; Sibai, B.M.; Hauth, J.; Lindheimer, M.D.; Klebanoff, M.; Thom, E.; van Dorsten, P.; Landon, M.; Paul, R.; Miodovnik, M.; Meis, P.; Thurnau, G. Low-dose aspirin to prevent preeclampsia in women at high risk. N. Engl. J. Med.？1998, 338, 701–705, doi:10.1056/NEJM199803123381101. 9494145
[26]
Lindheimer, M.D. Unraveling the mysteries of preeclampsia. Am. J. Obstet. Gynecol.？2005, 193, 3–4, doi:10.1016/j.ajog.2005.03.017. 16021050
[27]
Baron, J.A. Epidemiology of non-steroidal anti-inflammatory drugs and cancer. Prog. Exp. Tumor Res.？2003, 37, 1–24, doi:10.1159/000071364. 12795046
[28]
Flossman, E.; Rothwell, P.M. Effect of aspirin on long-term risk of colorectal cancer: consistent evidence from randomised and observational studies. Lancet？2007, 369, 1603–1613, doi:10.1016/S0140-6736(07)60747-8. 17499602
[29]
Chan, A.T.; Giovannuci, E.L.; Meyerhardt, J.A.; Schernhammer, E.S.; Curhan, G.C.; Wu, K.; Fuches, C.S. Aspirin dose and duration of use and risk of colorectal cancer in mean. Gastroenterology？2008, 134, 21–28, doi:10.1053/j.gastro.2007.09.035. 18005960
[30]
Chan, A.T.; Giovannuci, E.L.; Meyerhardt, J.A.; Schernhammer, E.S.; Curhan, G.C.; Fuches, C.S. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA？2005, 294, 914–923, doi:10.1001/jama.294.8.914. 16118381
[31]
Sandler, R.S.; Halabi, S.; Baron, J.A.; Budinger, S.; Paskett, E.; Keresztes, R.; Petrelli, N.; Pipas, J.M.; Karp, D.D.; Loprinzi, C.L.; Steinbach, G.; Schilsky, R. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. New Engl. J. Med.？2003, 348, 883–890, doi:10.1056/NEJMoa021633. 12621132
[32]
Logan, R.F.A.; Grainge, M.J.; Shepherd, V.C.; Armitage, N.C.; Muir, K.R. Aspirin and folic acid for the prevention of recurrent colorectal adenomas. Gastroenterology？2008, 134, 29–38, doi:10.1053/j.gastro.2007.10.014. 18022173
[33]
Benamouzig, R.; Deyra, J.; Martin, A.; Girard, B.; Jullian, E.; Piednoir, B.; Couturier, D.; Coste, T.; Little, J.; Chaussade, S. Daily soluble aspirin and prevention of colorectal adenomas recurrence: one-year results of the APACC trial. Gastroenterology？2003, 125, 328–336, doi:10.1016/S0016-5085(03)00887-4. 12891533
[34]
Khuder, S.A.; Mutgi, A.B. Breast cancer and NSAID use: A meta-analysis. Br. J. Cancer？2001, 84, 1188–1192, doi:10.1054/bjoc.2000.1709. 11336469
[35]
Gonzalez-Perez, A.; Garcia Rodriguez, L.A.; Lopez-Ridaura, R. Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. BMC Cancer？2003, 3, 28, doi:10.1186/1471-2407-3-28. 14588079
[36]
Coogan, P.F.; Rao, S.R.; Rosenberg, L.; Palmer, J.R.; Strom, B.L.; Zauber, A.G.; Stolley, P.D.; Shapiro, S. The relationship of nonsteroidal anti-inflammatory drug use to the risk of breast cancer. Prev. Med.？1999, 24, 107–109.
[37]
Egan, K.M.; Stampfer, M.J.; Giovannucci, E.; Rosner, B.A.; Colditz, G.A. Prospective study of regular aspirin use and the risk of breast cancer. J. Natl. Cancer Inst.？1996, 88, 988–933, doi:10.1093/jnci/88.14.988. 8667430
[38]
Harris, R.E.; Namboodiri, K.K.; Farrar, W.B. Nonsteroidal anti-inflammatory drugs and breast cancer. Epidemiology？1996, 7, 203–205, doi:10.1097/00001648-199603000-00017. 8834563
[39]
Neugut, A.I.; Rosenberg, D.J.; Ahsan, H.; Jacobson, J.S.; Wahid, N.; Hagan, M.; Rahman, M.I.; Khan, Z.R.; Chen, L.; Pablos-Mendez, A.; Shea, S. Association between coronary heart disease and cancers of the breast, prostate and colon. Cancer Epidemiol. Biomarkers Prev.？1998, 7, 869–873. 9796631
[40]
Harris, R.E.; Kasbari, S.; Farrar, W.B. Prospective study of non-steroidal anti-inflammatory drugs and breast cancer. Oncol. Rep.？1999, 6, 71–73. 9864404
[41]
Sharpe, C.R.; Collet, J.P.; McNutt, M.; Belzile, E.; Boivin, J.F.; Hanley, J.A. Nested case-control study of the effects of non-steroidal anti-inflammatory drugs on breast cancer risk and stage. Br. J. Cancer？2000, 83, 112–120, doi:10.1054/bjoc.2000.1119. 10883678
[42]
Langman, M.J.; Cheng, K.K.; Gilman, E.A.; Lancashire, R.J. Effect of anti-inflammatory drugs on overall risk of common cancer: Case-control study in general practice research database. Br. Med. J.？2000, 320, 1642–1646, doi:10.1136/bmj.320.7250.1642.
[43]
Meier, C.R.; Schmitz, S.; Jick, H. Association between acetaminophen or nonsteroidal anti-inflammatory drugs and risk of developing ovarian, breast, or colon cancer. Pharmacotherapy？2002, 22, 303–309, doi:10.1592/phco.22.5.303.33189. 11898889
[44]
Cotterchio, M.; Kreiger, N.; Sloan, M.; Steingart, A. Nonsteroidal anti-inflammatory drug use and breast cancer risk. Cancer Epidemiol. Biomarkers Prev.？2001, 10, 1213–1217. 11700271
[45]
Johnson, T.W.; Anderson, K.E.; Lazovich, D.; Folsom, A.R. Association of aspirin and non-steroidal anti-inflammatory drugs use with breast cancer. Cancer Epidemiol. Biomarkers Prev.？2002, 11, 1586–1591. 12496048
[46]
He, J.; Whelton, P.K.; Vu, B.; Klag, M.J. Aspirin and risk of hemorrhagic stroke: a meta-analysis of randomized controlled trials. JAMA？1998, 280, 1930–1935, doi:10.1001/jama.280.22.1930. 9851479
[47]
Derry, S.; Loke, Y.K. Risk of gastrointestinal haemorrhage with long term use of aspirin: a meta-analysis. BMJ？2000, 321, 1183–1187, doi:10.1136/bmj.321.7270.1183. 11073508
[48]
Bojar, R.M. Manual of Perioperative Care in Adult Cardiac Surgery; Blackwell: Malden, Oxford, UK, 2005.
[49]
Kallis, P.; Tooze, J.A.; Talbot, S.; Cowans, D.; Bevan, D.H.; Treasure, T. Pre-operative aspirin decreases platelet aggregation and increase post-operative blood loss-a prospective randomised, placebo controlled, double-blind clinical trial in 1000 patients with chronic stable angina. Eur. J. Cardio-Thorac. Surg.？1994, 8, 404–409, doi:10.1016/1010-7940(94)90081-7.
[50]
Morawski, W.; Sanak, M.; Cisowski, M.; Szczeklik, M.; Szczeklik, W.; Dropinski, J.; Waclawczyk, T.; Ulczok, R.; Bochenek, A. Prediction of the excess perioperative bleeding in patients undergoing coronary artery bypass grafting: role of aspirin and platelet glycoprotein IIa polymorphism. J. Thorac. Cardiovasc. Surg.？2005, 130, 791–796, doi:10.1016/j.jtcvs.2005.02.041. 16153930
[51]
Sethi, G.K.; Copeland, J.G.; Goldman, S.; Moritz, T.; Zadina, K.; Henderson, W.G. Implications of preoperative administration of aspirin in patients undergoing coronary artery bypass grating. Department of Veterans Affairs Cooperative Study on Antiplatelet Therapy. J. Am. Coll. Cardiol.？1990, 15, 15–20, doi:10.1016/0735-1097(90)90168-O. 2404046
[52]
Reich, D.L.; Patel, G.C.; Vela-Cantos, F.; Bodian, C.; Lansman, S. Aspirin dose not increase homologous blood requirements in elective coronary bypass surgery. Anesth. Analg.？1994, 79, 4–8, doi:10.1213/00000539-199407000-00002. 8010451
[53]
Veylsteke, A.; Oduro, A.; Cardan, E.; Latimer, R.D. Effect of aspirin in coronary artery bypass grafting. J. Cardiothorac. Vasc. Anaesth.？1997, 11, 831–834, doi:10.1016/S1053-0770(97)90115-4.
[54]
Dacey, L.J.; Munoz, J.J.; Johnson, E.R.; Leavitt, B.J.; Maloney, C.T.; Morton, J.R.; Olmstead, E.M.; Birkmeyer, J.D.; O’Connor, G.T. Effect of preoperative aspirin use on mortality in coronary artery bypass grafting patients. Ann. Thorac. Surg.？2000, 70, 1986–1990, doi:10.1016/S0003-4975(00)02133-0. 11156107
De Berardis, G.; Sacco, M.; Strippoli, G.F.M.; Pellegrini, F.; Graziano, G.; Tognoni, G.; Nicolucci, A. Aspirin for the primary prevention of cardiovascular events in people with diabetes: meta-analysis of randomised controlled trials. BMJ？2009, 339, b4531. 19897665
[57]
Berger, J.S.; Krantz, M.J.; Kittelson, J.M.; Hiatt, W.R. Aspirin for the prevention of cardiovascular events in patients with peripheral artery disease: a meta-analysis or randomized trials. JAMA？2009, 301, 1909–1919, doi:10.1001/jama.2009.623. 19436018
[58]
Askie, L.M.; Duley, L.; Henderson-Smart, D.J.; Stewart, L.A. of the PAIRS Collaborative Group. Antiplatelet agents for prevention of pre-eclampsia: meta-analysis of individual patient data. Lancet？2007, 369, 1791–1798. 17512048
[59]
Bujold, E.; Morency, A.-M.; Roberge, S.; Lacasse, Y.; Forest, J.-C.; Giguere, Y. Acetylsalicylic acid for the prevention of preeclampsia and intra-uterine growth restriction in women with abnormal uterine artery Doppler: a systematic review and meta-analysis. J. Obstet. Gynaecol. Can.？2009, 31, 818–826. 19941706
[60]
Cole, B.F.; Logan, R.F.; Halabi, S.; Benamouzig, R.; Sandler, R.S.; Grainge, M.J.; Chaussade, S.; Baron, J.A. Aspirin for the chemoprevention of colorectal adenomas: a meta-analysis of the randomized trials. J. Natl. Cancer. Inst.？2009, 101, 256–266, doi:10.1093/jnci/djn485. 19211452
[61]
Mangiapane, S.; Blettner, M.; Schlattmann, P. Aspirin use and breast cancer risk: a meta-analysis and meta-regression of observational studies from 2001 to 2005. Pharmacoepidemiol. Drug Saf.？2008, 17, 115–124, doi:10.1002/pds.1503. 17955496
[62]
Alghamdi, A.A.; Moussa, F.; Fremes, S.E. Does the use of preoperative aspirin increase the risk of bleeding in patients undergoing coronary artery bypass grafting surgery? Systematic review and meta-analysis. J. Card. Surg.？2007, 22, 247–256, doi:10.1111/j.1540-8191.2007.00402.x. 17488432
[63]
Lewis, K.G.; Dufresne, R.G., Jr. A meta-analysis of complications attributed to anticoagulation among patients following cutaneous surgery. Dermatol. Surg.？2008, 34, 160–165. 18093204
[64]
Syed, S.; Adams, B.B.; Liao, W.; Pipitone, M.; Gloster, H. A prospective assessment of bleeding and international normalized ratio in warfarin-anticoagulated patients having cutaneous surgery. J. Am. Acad. Dermtol.？2004, 51, 955–957, doi:10.1016/j.jaad.2004.07.058.
[65]
Kargi, E.; Babuccu, O.; Hosnuter, M.; Babuccu, B.; Altinyazar, C. Complications of minor cutaneous surgery in patients under anticoagulant treatment. Aesthet. Plast. Surg.？2002, 26, 483–485, doi:10.1007/s00266-002-2055-1.
[66]
Alcalay, J. Cutaneous surgery in patients receiving warfarin therapy. Dermatol. Surg.？2001, 27, 756–758, doi:10.1046/j.1524-4725.2001.01056.x. 11493301
[67]
Alam, M.; Goldberg, L.H. Serious adverse vascular events associated with perioperative interruptions of antiplatelet and anticoagulant therapy. Dermatol. Surg.？2002, 28, 992–998. discussion 998, doi:10.1046/j.1524-4725.2002.02085.x. 12460291
[68]
Walker, J.; Robinson, J.; Stewart, J.; Jacob, S. Does enteric-coated aspirin result in a lower incidence of gastrointestinal complications compared to normal aspirin? Interact Cardiovasc Thorac Surg.？2007, 6, 519–522, doi:10.1510/icvts.2007.155788. 17669925
[69]
Straube, S.; Tramèr, M.R.; Moore, R.A.; Derry, S.; McQuay, H.J. Mortality with upper gastrointestinal bleeding and perforation: effects of time and NSAID use. BMC Gastroenterol.？2009, 5, 9–41.
