Aspirin resistance: causes, clinical significance, correction

Authors

  • G.F. Gendeleka Odesa National Medical University, Odesa, Ukraine https://orcid.org/0000-0002-5879-9279
  • A.N. Gendeleka Municipal Non-Profit Enterprise “Primary Health Care Centre 5”, Odesa, Ukraine

DOI:

https://doi.org/10.22141/2224-0721.18.2.2022.1157

Keywords:

aspirin, antiplatelet treatment, aspirin resistance, acetylsalicylic acid, platelet aggregation

Abstract

Aspirin is the most frequently prescribed antiplatelet agent today. It exerts its antiplatelet effect by irreversible inactivation of the platelet cyclooxygenase-1, resulting in an irreversible inhibition of thromboxane-A2 formation. The clinical benefit of antiplatelet therapy with acetylsalicylic acid (ASA) in high risk patients has been convincingly demonstrated through the results of multiple placebo-controlled trials. Nevertheless, a large number of patients treated with aspirin suffers an adverse cardiovascular event. This observation led to the concept of ”aspirin resistance“. The mechanisms of aspirin resistance remain to be determined, although different theories are being discussed. Several tests are used to assess resistance to ASA in vitro. Depending on which assay is used and which population is tested, the prevalence of aspirin resistance varies between 5 % and 60 %. So far, it was not possible to define a clear gold standard for detecting aspirin resistance, which considers both, biochemical data and clinical events, and correlates them in a reproducible way. The clinical implications of aspirin resistance are well-documented through a lot of studies, which conclude that resistance to aspirin in vitro is associated with a significant increased risk for adverse cardiovascular events in cardiovascular patients. Insufficient or excessive antiplatelet effect of acetylsalicylacid may be due not only to changes in the synthesized cyclooxygenase-1, but also to changes in its amount. Literature data on the association of various polymorphic markers of candidate genes with the effectiveness of antiplatelet therapy of ASA are few and contradictory. Therefore, it is currently impossible to identify genetic predictors of the effectiveness of ASA as well as any antiplatelet agent. Continuation of research in this area in the future will predict the patient’s response to a drug and, therefore, individualize the approach to the choice and dosage of antiplatelet drugs, which will reduce the incidence of adverse reactions.

Downloads

Download data is not yet available.

References

Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov. 2003;2(1):15-28. doi: 10.1038/nrd985.

Mehta JL, Mohandas B. Aspirin resistance: Fact or fiction? A point of view. World J Cardiol. 2010;2(9):280-8. doi: 10.4330/wjc.v2.i9.280.

Kim KE, Woo KS, Goh RY, Quan ML, Cha KS, Kim MH, Han JY. Comparison of laboratory detection methods of aspirin resistance in coronary artery disease patients. Int J Lab Hematol. 2010;32(1 Pt 2):50-5. doi: 10.1111/j.1751-553X.2008.01119.x.

Du G, Lin Q, Wang J. A brief review on the mechanisms of aspirin resistance. Int J Cardiol. 2016;220:21-6. doi: 10.1016/j.ijcard.2016.06.104.

Floyd CN, Ferro A. Mechanisms of aspirin resistance. Pharmacol Ther. 2014;141(1):69-78. doi: 10.1016/j.pharmthera.2013.08.005.

Friend M, Vucenik I, Miller M. Research pointers: Platelet responsiveness to aspirin in patients with hyperlipidaemia. BMJ. 2003;326(7380):82-3. doi: 10.1136/bmj.326.7380.82.

Macchi L, Sorel N, Christiaens L. Aspirin resistance: definitions, mechanisms, prevalence, and clinical significance. Curr Pharm Des. 2006;12(2):251-8. doi: 10.2174/138161206775193064.

Rolando B, Lazzarato L, Donnola M, et al. Water-soluble nitric-oxide-releasing acetylsalicylic acid (ASA) prodrugs. Chem Med Chem. 2013;8(7):1199-209. doi: 10.1002/cmdc.201300105.

Alsop RJ, Barrett MA, Zheng S, Dies H, Rheinstädter MC. Acetylsalicylic acid (ASA) increases the solubility of cholesterol when incorporated in lipid membranes. Soft Matter. 2014;10(24):4275-86. doi: 10.1039/c4sm00372a.

Nokhodchi A, Ghafourian T, Nashed N, et al. Solubility Study of Acetylsalicylic Acid in Ethanol + Water Mixtures: Measurement, Mathematical Modeling, and Stability Discussion. AAPS Pharm Sci Tech. 2021;23(1):42. doi: 10.1208/s12249-021-02192-7.

Peltonen L, Liljeroth P, Heikkilä T, Kontturi K, Hirvonen J. Dissolution testing of acetylsalicylic acid by a channel flow method-correlation to USP basket and intrinsic dissolution methods. Eur J Pharm Sci. 2003;19(5):395-401. doi: 10.1016/s0928-0987(03)00140-4.

Suwalsky M, Belmar J, Villena F, Gallardo MJ, Jemiola-Rzeminska M, Strzalka K. Acetylsalicylic acid (aspirin) and salicylic acid interaction with the human erythrocyte membrane bilayer induce in vitro changes in the morphology of erythrocytes. Arch Biochem Biophys. 2013;539(1):9-19. doi: 10.1016/j.abb.2013.09.006.

Zimmermann P, Curtis N. The effect of aspirin on antibiotic susceptibility. Expert Opin Ther Targets. 2018 Nov;22(11):967-972. doi: 10.1080/14728222.2018.1527314.

Di Bella S, Luzzati R, Principe L, et al. Aspirin and Infection: A Narrative Review. Biomedicines. 2022;10(2):263. doi: 10.3390/biomedicines10020263.

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 Jan 22;127(3):377-85. doi: 10.1161/CIRCULATIONAHA.112.117283.

Cotter G, Shemesh E, Zehavi M, et al. Lack of aspirin effect: aspirin resistance or resistance to taking aspirin? Am Heart J. 2004;147(2):293-300. doi: 10.1016/j.ahj.2003.07.011.

Ohmori T, Yatomi Y, Nonaka T, et al. Aspirin resistance detected with aggregometry cannot be explained by cyclooxygenase activity: involvement of other signaling pathway(s) in cardiovascular events of aspirin-treated patients. J Thromb Haemost. 2006;4(6):1271-8. doi: 10.1111/j.1538-7836.2006.01958.x.

Undas A, Placzkiewicz-Jankowska E, Zieliński L, Tracz W. Lack of aspirin-induced decrease in thrombin formation in subjects resistant to aspirin. Thromb Haemost. 2007 Jun;97(6):1056-8.

Dawson J, Quinn T, Rafferty M, et al. Aspirin resistance and compliance with therapy. Cardiovasc Ther. 2011;29(5):301-7. doi: 10.1111/j.1755-5922.2010.00188.x.

Grinstein J, Cannon CP. Aspirin resistance: current status and role of tailored therapy. Clin Cardiol. 2012;35(11):673-81. doi: 10.1002/clc.22031.

Anfossi G, Russo I, Trovati M. Platelet resistance to the anti-aggregating agents in the insulin resistant states. Curr Diabetes Rev. 2006 Nov;2(4):409-30. doi: 10.2174/1573399810602040409.

ASCEND Study Collaborative Group, Bowman L, Mafham M, Wallendszus K, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018;379(16):1529-1539. doi: 10.1056/NEJMoa1804988.

Halushka MK, Walker LP, Halushka PV. Genetic variation in cyclooxygenase 1: effects on response to aspirin. Clin Pharmacol Ther. 2003 Jan;73(1):122-30. doi: 10.1067/mcp.2003.1.

Macchi L, Sorel N, Christiaens L. Aspirin resistance: definitions, mechanisms, prevalence, and clinical significance. Curr Pharm Des. 2006;12(2):251-8. doi: 10.2174/138161206775193064.

Eikelboom JW, Hankey GJ. Aspirin resistance: a new independent predictor of vascular events? J Am Coll Cardiol. 2003 Mar 19;41(6):966-8. doi: 10.1016/s0735-1097(02)03013-9.

Published

2022-04-22

How to Cite

Gendeleka, G., & Gendeleka, A. (2022). Aspirin resistance: causes, clinical significance, correction. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), 18(2), 118–123. https://doi.org/10.22141/2224-0721.18.2.2022.1157

Issue

Section

Literature Review

Most read articles by the same author(s)