To access this material please log in or register

Register Authorize

Resistance to antiplatelet agents

Bokarev I. N., Popova L. V.

Keywords: antiplatelet therapy, hemostasis, resistance

DOI: 10.18087/rhj.2012.2.1691

Antiplatelet agents inhibit the formation of blood clots in arteries and thus are widely administered to prevent atherothrombosis of different localization. The main agents of the antiaggregant group that showed their efficacy in a considerable number of clinical studies are acetylsalicylic acid and Clopidogrel. Nevertheless, deterioration of clinical results is observed in some cases, which is probably connected with insufficient inhibition of platelet function against administration of these agents, which is detected by laboratory tests. This phenomenon was named a resistance to Aspirin or Clopidogrel. There are various reasons. However, many questions concerning this phenomenon, such as its detection, criteria of laboratory diagnostics, laboratory tests, and even the possibility of this phenomenon’s influence on the clinical outcomes, are still actively discussed in the research literature.
  1. Müller I, Besta F, Schulz C et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost. 2003;89 (5):783–787.
  2. Hennekens CH, Schror K, Weisman S, FitzGerald GA. Terms and conditions: semantic complexity and aspirin resistance. Circulation. 2004;110 (12):1706–1708.
  3. Gurbel PA, Tantry US. Clopidogrel resistance? Thromb Res. 2007;120 (3):311–321.
  4. Andre P, Delaney SM, LaRocca T et al. P2Y12 regulates platelet adhesion / activation, thrombus growth, and thrombus stability in injured arteries. J Clin Invest. 2003;112 (3):398–406.
  5. Kuliczkowski W, Witkowski A, Polonski L et al. Interindividual variability in the response to oral antiplatelet drugs: a position paper of the Working Group on antiplatelet drugs resistance appointed by the Section of Cardiovascular Interventions of the Polish Cardiac Society, endorsed by the Working Group on Thrombosis of the European Society of Cardiology. Eur Heart J. 2009;30 (4):426–435.
  6. Dupont AG, Gabriel DA, Cohen MG. Antiplatelet therapies and the role of antiplatelet resistance in acute coronary syndrome. Thromb Res. 2009;124 (1):6–13.
  7. Musallam KM, Charafeddine K, Bitar A et al. Resistance to aspirin and clopidogrel therapy. Int J Lab Hematol. 2011;33 (1):1–18.
  8. Lordkipanidzé M, Pharand C, Schampaert E et al. A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J. 2007;28 (14):1702–1708.
  9. Gawaz M, Bigalke B, Fateh-Moghadam S et al. Blood platelets – clinical relevance. – Georg Thieme Verlag Stuttgart. New York – p 92.
  10. Biondi-Zoccai GG, Lotrionte M, Agostoni P et al. A 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):2667–2674.
  11. Dropinski J, Musial J, Sanak M et al. Anti-thrombotic effects of aspirin based on PLA1 / A2 glycoprotein IIIa polymorphism in patients with coronary artery disease. Thromb Res. 2007;119 (3):301–303.
  12. Montalescot G, Wiviott SD, Braunwald E et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet. 2009;373 (9665):723–731.
  13. European Association for Percutaneous Cardiovascular Interventions. 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). Eur Heart J. 2010 Oct;31 (20):2501–2555.
  14. Bhatt DL, Scheiman J, Abraham NS et al. American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2008;52 (18):1502–1517.
  15. Saw J, Steinhubl SR, Berger PB et al. Clopidogrel for the Reduction of Events During Observation Investigators. Lack of adverse clopidogrel-atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial. Circulation. 2003;108 (8):921–924.
  16. Cattaneo M. Resistance to antiplatelet drugs: molecular mrchanism and laboratory detection. J Thromb Haemost. 2007;5 (Suppl 1):230–237.
  17. Krasopoulos G, Brister SJ, Beattie WS, Buchanan MR. Aspirin «resistance» and risk of cardiovascular morbidity: systematic review and meta-analysis. BMJ. 2008;336 (7637):195–198.
  18. Boncoraglio GB, Bodini A, Brambilla C et al. Aspirin resistance determined with PFA-100 does not predict new thrombotic events in patients with stable ischemic cerebrovascular disease. Clin Neurol Neurosurg. 2009;111 (3):270–273.
  19. Lee PY, Chen WH, Ng W et al. Low-dose aspirin increases aspirin resistance in patients with coronary artery disease. Am J Med. 2005;118 (7):723–727.
  20. Mehta SR, Tanguay JF, Eikelboom JW et al, CURRENT-OASIS 7 trial investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet. 2010;376 (9748):1233–1243.
  21. Price MJ, Berger PB, Teirstein PS et al. GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011;305 (11):1097–1105.
  22. Ohman EM, Roe MT. Explaining the unexpected: insights from the PLATelet inhibition and clinical Outcomes (PLATO) trial compa­ring ticagrelor and clopidogrel. Editorial on Serebruany «Viewpoint: Paradoxical excess mortality in the PLATO trial should be independently verified» (Thromb Haemost 2011; 105.5). Thromb Haemost. 2011;105 (5):763–765.
  23. Shim CY, Yoon SJ, Park S et al. The clopidogrel resistance can be attenuated with triple antiplatelet therapy in patients undergoing drug-eluting stents implantation. Int J Cardiol. 2009;134 (3):351–355.
Bokarev I. N., Popova L. V. Resistance to antiplatelet agents. Russian Heart Journal. 2012;11(2):103-107

To access this material please log in or register

Register Authorize
Ru En