Is Aspirin Still the Cornerstone of Antiplatelet Therapy in Patients With Coronary Artery Disease? An Historical and Practical Narrative Review

Document Type: Review Article

Authors

1 Division of Cardiology, A.O.U San Luigi Gonzaga, Orbassano, Torino, Italy

2 Interventional Cardiology Unit, Infermi Hospital, Rivoli and San Luigi Gonzaga University Hospital, Orbassano, Italy

3 Dipartimento di Scienze Mediche, Divisione di Cardiologia, Città della Salute e della Scienza, Turin, Italy

Abstract

Aspirin is an irreversible and non-selective inhibitor of cyclo-oxygenase. It represents the cornerstone of antiplatelet therapy and is used in secondary prevention of cardiovascular disease. Disagreement over the optimal maintenance dosage still exists; in America and Europe the most used doses of aspirin are 81 mg and 100 mg daily, respectively. There is also debate on the formulation and route of administration of the loading dose. The latest studies advise chewable and non-enteric coated aspirin; intravenous administration represents an alternative for unconscious or shocked patients. Aspirin hypersensitivity is characterized by the onset of respiratory, mucocutaneous, and systemic symptoms. It is marginally considered, but its prevalence is significant. International cardiologic guidelines only report the possibility of desensitizing intolerant patients or, alternatively, administering one single antiplatelet agent. Desensitization can induce a temporary tolerance to the drug and consists of the administration of sequential and incremental doses of aspirin. Rapid desensitization protocols have proven to be safe and effective in the vast majority of cases, and they should be included in the management of these patients. New studies are being carried out comparing aspirin with other antiplatelet agents, and the results will be available shortly.

Keywords


  1. Vane JR, Botting RM. The mechanism of action of aspirin. Thromb Res. 2003;110(5-6):255-258. doi: 10.1016/S0049-3848(03)00379-7.
  2. Vane JR, Botting RM. Aspirin and Other Salicylates. London: Chapman & Hall Medical; 1992.
  3. Gilroy DW. The role of aspirin-triggered lipoxins in the mechanism of action of aspirin. Prostaglandins Leukot Essent Fatty Acids. 2005;73(3-4):203-10. doi:10.1016/j.plefa.2005.05.007.
  4. Katzung BG. Basic & Clinical Pharmacology. 10th ed. New York: McGraw-Hill Professional; 2006.
  5. Baigent C, Collins R, Appleby P, Parish S, Sleight P, Peto R. ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither. The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. BMJ. 1998;316(7141):1337-1343. doi:10.1136/bmj.316.7141.1337.
  6. Mehta SR, Tanguay JF, Eikelboom JW, et al. Double-dose versus standard-dose clopidogrel and high-dose versus lowdose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010;376(9748):1233-1243. doi:10.1016/S0140-6736(10)61088-4.
  7. 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. Antiplatelet Trialists’ Collaboration. BMJ. 1994;308(6921):81-106. doi:10.1136/bmj.308.6921.81.
  8. Dalen JE. Aspirin to prevent heart attack and stroke: what’s the right dose? Am J Med. 2006;119(3):198-202. doi:10.1016/j.amjmed.2005.11.013.
  9. DiNicolantonio JJ, Norgard NB, Meier P, et al. Optimal aspirin dose in acute coronary syndromes: an emerging consensus. Future Cardiol. 2014;10(2):291-300. doi:10.2217/fca.14.7.
  10. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization: The Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J. 2014;35(37):2541-2619. doi:10.1093/eurheartj/ehu278.
  11. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol. 2011;58(24):e44-e122. doi:10.1016/j.jacc.2011.08.007.
  12. Bem D, Dretzke J, Stevens S, et al. Investigating the effectiveness of different aspirin dosing regimens and the timing of aspirin intake in primary and secondary prevention of cardiovascular disease: protocol for a systematic review. Syst Rev. 2015;4:88. doi:10.1186/s13643-015-0078-3.
  13. Biondi-Zoccai G, Lotrionte M, Agostoni P, et al. Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes. Int J Cardiol. 2011;150(3):325-331. doi:10.1016/j.ijcard.2010.08.035.
  14. D’Ascenzo F, Barbero U, Bisi M, et al. The prognostic impact of high on-treatment platelet reactivity with aspirin or ADP receptor antagonists: systematic review and meta-analysis. Biomed Res Int. 2014;2014:610296. doi:10.1155/2014/610296.
  15. D’Ascenzo F, Taha S, Moretti C, et al. Meta-analysis of randomized controlled trials and adjusted observational results of use of clopidogrel, aspirin, and oral anticoagulants in patients undergoing percutaneous coronary intervention. Am J Cardiol. 2015;115(9):1185-1193. doi:10.1016/j.amjcard.2015.02.003.
  16. Bollati M, Gaita F, Anselmino M. Antiplatelet combinations for prevention of atherothrombotic events. Vasc Health Risk Manag. 2011;7:23-30. doi:10.2147/VHRM.S12271.
  17. D’Ascenzo F, Colombo F, Barbero U, et al. Discontinuation of dual antiplatelet therapy over 12 months after acute coronary syndromes increases risk for adverse events in patients treated with percutaneous coronary intervention: systematic review and meta-analysis. J Interv Cardiol. 2014;27(3):233-241. doi:10.1111/joic.12107.
  18. Grosser T, Fries S, Lawson JA, Kapoor SC, Grant GR, FitzGerald GA. Drug resistance and pseudoresistance: an unintended consequence of enteric coating aspirin. Circulation. 2013;127(3):377-385. doi:10.1161/CIRCULATIONAHA.112.117283.
  19. 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. 2012;44(10):833-838. doi:10.1016/j.dld.2012.05.016.
  20. Hobl EL, Schmid RW, Stimpfl T, Ebner J, Jilma B. Absorption kinetics of low-dose chewable aspirin--implications for acute coronary syndromes. Eur J Clin Invest. 2015;45(1):13-17. doi:10.1111/eci.12373.
  21. Nordt SP, Clark RF, Castillo EM, Guss DA. Comparison of three aspirin formulations in human volunteers. West J Emerg Med. 2011;12(4):381-385. doi:10.5811/westjem.2011.4.2222.
  22. Vivas D, Martin A, Bernardo E, et al. Impact of intravenous lysine acetylsalicylate versus oral aspirin on prasugrel-inhibited platelets: results of a prospective, randomized, crossover study (the ECCLIPSE Trial). Circ Cardiovasc Interv. 2015;8(5). doi:10.1161/CIRCINTERVENTIONS.114.002281.
  23. Ganjehei L, Becker RC. Aspirin dosing in cardiovascular disease prevention and management: an update. J Thromb Thrombolysis. 2015;40(4):499-511. doi:10.1007/s11239-015-1267-6.
  24. National Institute for Health and Clinical Excellence. Clopidogrel and modified release dipyridamole in the prevention of occlusive vascular events. Published 2005.
  25. Bianco M, Bernardi A, D’Ascenzo F, et al. Efficacy and safety of available protocols for aspirin hypersensitivity for patients undergoing percutaneous coronary intervention: a survey and systematic review. Circ Cardiovasc Interv. 2016;9(1):e002896. doi:10.1161/CIRCINTERVENTIONS.115.002896.
  26. Castells M. Desensitization for drug allergy. Curr Opin Allergy Clin Immunol. 2006;6(6):476-481. doi:10.1097/ACI.0b013e3280108716.
  27. Lambrakis P, Rushworth GF, Adamson J, Leslie SJ. Aspirin hypersensitivity and desensitization protocols: implications for cardiac patients. Ther Adv Drug Saf. 2011;2(6):263-270. doi:10.1177/2042098611422558.
  28. Silberman S, Neukirch-Stoop C, Steg PG. Rapid desensitization procedure for patients with aspirin hypersensitivity undergoing coronary stenting. Am J Cardiol. 2005;95(4):509-510. doi:10.1016/j.amjcard.2004.10.022.
  29. Jenneck C, Juergens U, Buecheler M, Novak N. Pathogenesis, diagnosis, and treatment of aspirin intolerance. Ann Allergy Asthma Immunol. 2007;99(1):13-21. doi:10.1016/S1081-1206(10)60615-1.
  30. Gollapudi RR, Teirstein PS, Stevenson DD, Simon RA. Aspirin sensitivity: implications for patients with coronary artery disease. JAMA. 2004;292(24):3017-3023. doi:10.1001/jama.292.24.3017.
  31. Ramanuja S, Breall JA, Kalaria VG. Approach to “aspirin allergy” in cardiovascular patients. Circulation. 2004;110(1):e1-e4. doi:10.1161/01.CIR.0000134306.28561.2A.
  32. Stevenson DD, Szczeklik A. Clinical and pathologic perspectives on aspirin sensitivity and asthma. J Allergy Clin Immunol. 2006;118(4):773-786. doi:10.1016/j.jaci.2006.07.024.
  33. Solensky R. Drug desensitization. Immunol Allergy Clin North Am. 2004;24(3):425-443. doi:10.1016/j.iac.2004.03.008.
  34. De Luca G, Verdoia M, Binda G, Schaffer A, Suryapranata H, Marino P. Aspirin desensitization in patients undergoing planned or urgent coronary stent implantation. A single-center experience. Int J Cardiol. 2013;167(2):561-563. doi:10.1016/j.ijcard.2012.01.063.
  35. Cortellini G, Testi S, Severino M, et al. Aspirin challenge/desensitisation before coronary stenting in subjects with history of hypersensitivity. A pragmatic approach. Eur Ann Allergy Clin Immunol. 2012;44(4):160-162.
  36. Lee JK, Tsui KL, Cheung CY, et al. Aspirin desensitisation for Chinese patients with coronary artery disease. Hong Kong Med J. 2013;19(3):207-213. doi:10.12809/hkmj133914.
  37. Rossini R, Angiolillo DJ, Musumeci G, et al. Aspirin desensitization in patients undergoing percutaneous coronary interventions with stent implantation. Am J Cardiol. 2008;101(6):786-789. doi:10.1016/j.amjcard.2007.10.045.
  38. Silberman S, Neukirch-Stoop C, Steg PG. Rapid desensitization procedure for patients with aspirin hypersensitivity undergoing coronary stenting. Am J Cardiol. 2005;95(4):509-510. doi:10.1016/j.amjcard.2004.10.022.
  39. Veas PN, Martinez G, Jalil MJ, Martinez SA, Castro GP. [Rapid aspirin desensitization in patients with a history of aspirin hypersensitivity requiring coronary angioplasty. Report of four cases]. Rev Med Chil. 2013;141(2):255-259. doi:10.4067/S0034-98872013000200016.
  40. Christou A, Kafkas N, Marinakos A, Katsanos S, Papanikitas K, Patsilinakos S. Rapid desensitisation of patients with aspirin allergy who undergo coronary angioplasty. Hellenic J Cardiol. 2011;52(4):307-310.
  41. Dalmau G, Gaig P, Gazquez V, Merce J. Rapid desensitization to acetylsalicylic acid in acute coronary syndrome patients with NSAID intolerance. Rev Esp Cardiol. 2009;62(2):224-225. doi:10.1016/S0300-8932(09)70167-8.
  42. Wong JT, Nagy CS, Krinzman SJ, Maclean JA, Bloch KJ. Rapid oral challenge-desensitization for patients with aspirinrelated urticaria-angioedema. J Allergy Clin Immunol. 2000;105(5):997-1001. doi:10.1067/mai.2000.104571.
  43. McMullan KL, Wedner HJ. Safety of aspirin desensitization in patients with reported aspirin allergy and cardiovascular disease. Clin Cardiol. 2013;36(1):25-30. doi:10.1002/clc.22054.
  44. Cordoba-Soriano JG, Corbi-Pascual M, Lopez-Neyra I, Navarro-Cuartero J, Hidalgo-Olivares V, Barrionuevo-Sanchez MI, et al. Early aspirin desensitization in unstable patients with acute coronary syndrome: Short and long-term efficacy and safety. Eur Heart J Acute Cardiovasc Care. 2016;5(7):41-50. doi:10.1177/2048872615618509.
  45. D’Ascenzo F, Moretti C, Bianco M, et al. Meta-analysis of the duration of dual antiplatelet therapy in patients treated with second-generation drug-eluting stents. Am J Cardiol. 2016;117(11):1714-1723. doi:10.1016/j.amjcard.2016.03.005.
  46. Rossini R, Iorio A, Pozzi R, et al. Aspirin desensitization in patients with coronary artery disease: results of the multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease). Circ Cardiovasc Interv. 2017;10(2). doi:10.1161/CIRCINTERVENTIONS.116.004368.
  47. Sweetman SC. Martindale: The Complete Drug Reference. 36th ed. London: Pharmaceutical Press; 2009.
  48. Lang DM. Do beta-blockers really enhance the risk of anaphylaxis during immunotherapy? Curr Allergy Asthma Rep. 2008;8(1):37-44. doi:10.1007/s11882-008-0008-8.
  49. TenBrook JA Jr, Wolf MP, Hoffman SN, et al. Should beta-blockers be given to patients with heart disease and peanut-induced anaphylaxis? A decision analysis. J Allergy Clin Immunol. 2004;113(5):977-982. doi:10.1016/j.jaci.2004.02.043.
  50. Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions--guidelines for healthcare providers. Resuscitation. 2008;77(2):157-169. doi:10.1016/j.resuscitation.2008.02.001.
  51. AstraZeneca UK Ltd. Zestril tablets: summary of product characteristics. http://www.medicines.ie/medicine/4387/SPC/Zestril+Tablets/. Published 2010.
  52. Varbella F, Musumeci G, Marchese A, Tarantini G. Ottimizzazione della terapia antiaggregante nelle sindromi coronariche acute. Edizioni Minerva Medica; 2011:1-10.
  53. Bibbins-Domingo K. Aspirin use for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016;164(12):836-845. doi:10.7326/M16-0577.
  54. Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 2012;9(5):259-267. doi:10.1038/nrclinonc.2011.199.
  55. Elwood PC, Morgan G, Pickering JE, et al. Aspirin in the treatment of cancer: reductions in metastatic spread and in mortality: a systematic review and meta-analyses of published studies. PLoS One. 2016;11(4):e0152402. doi:10.1371/journal.pone.0152402.
  56. Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826):1591-1601. doi:10.1016/S0140-6736(12)60209-8.
  57. 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.
  58. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381(9872):1107-15. doi:10.1016/S0140-6736(12)62177-1.
  59. Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(3):267-315. doi:10.1093/eurheartj/ehv320.
  60. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348(9038):1329-139. doi:10.1016/S0140-6736(96)09457-3.
  61. Johnston SC, Amarenco P, Albers GW, et al. Ticagrelor versus aspirin in acute stroke or transient ischemic attack. N Engl J Med. 2016;375(1):35-43. doi:10.1056/NEJMoa1603060.