DOI: 10.25881/BPNMSC.2020.20.88.016


Salukhov V.V.1, Gulayev N.I.2, Chepel A.I.1, Zemlyanoy A.B.3, Dorokhina E.V.1

1 Military Medical Academy. S.M. Kirov of the Ministry of Defense of Russia, St. Petersburg

2 3 Central Military Clinical Hospital named after A.A. Vishnevsky Ministry of Defense of Russia, Krasnogorsk

3 Pirogov National Medical and Surgical Center, Moscow


Antiplatelet therapy in patients with coronary artery disease seems to be a complex clinical and pharmacological task due to the different sensitivity of patients to treatment and the complexity of control of therapy.

The review presents literature data on platelet resistance to antiplatelet therapy and its complications. The options for modifying antiplatelet therapy, ways of overcoming resistance and increasing its effectiveness are considered.

Keywords: IHD, antiplatelet therapy cardiovascular complications, primary prevention, acetylsalicylic acid.


1. World Health Organization [Electronic resource]: official. website / WHO. URL (In Russ).

2. Mozaffarian D, Benjamin E, Go A, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2015 Jan 27; 131(4): 29–322. doi: 10.1161/CIR.0000000000000152.

3. Naghavi M, Wang H, Lozano R, Davis A, et al. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Jan 10; 385(9963): 117–71. doi: 10.1016/S0140-6736(14)61682-2.

4. Rosstat. [Electronic resource]: official site / Rosstat. URL (In Russ).

5. Rosstat. [Electronic resource]: official site / Rosstat. URL on 22.06.2019 (In Russ).

6. Naghavi M, Wang H, Lozano R, Davis A. et al. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013. Lancet. 2015 Jan 10; 385(9963): 117–71. doi: 10.1016/S0140-6736(14)61682-2.

7. Grines CL, Bonow RO, Casey DJr, et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents. J Am Dent Assoc. 2007 May; 138(5): 652–5. doi: 10.14219/jada.archive.2007.0237.

8. Vila P, Zafar M, Badimon J. Platelet reactivity and nonresponse to dual antiplatelet therapy. Platelets. 2009 Dec; 20(8): 531–8. doi: 10.3109/09537100903261379.

9. Sulimov VA, Moroz EV. Resistance to antiplatelet drugs in patients with coronary artery disease. Cardiovascular therapy and prevention. 2012; 11(6): 71–77. (In Russ).

10. World Health Report 2007. Prevention of Cardiovascular Disease. Guidelines for assessment and management of cardiovascular risk. World Health Organization, 2007; 35.

11. Patrono C. Aspirin resistance: definition, mechanisms and clinical readouts. J Thromb Haemost. 2003 Aug; 1(8): 1710-3. doi: 10.1046/j.1538-7836.2003.00284.x.

12. Tanashyan MM, Domashenko MA, Raskurazhev AA. Aspirin resistance: clinical and molecular genetic assessment methods. Annals of Clinical and Experimental Neurology. 2016; (10): 41–46. (In Russ).

13. Michelson AD, Cattaneo M, Eikelboom JW et al. Aspirin Resistance: Aspirin resistance: position paper of the Working Group on Aspirin Resistance. J Thromb Haemost. 2005 Jun; 3(6): 1309–11. doi: 10.1111/j.1538-7836.2005.01351.x.

14. Weber AA, Przytulski B, Schanz A, et al. Towards definition of aspirin resistance: a typologycal approach. Platelets. 2002 Feb; 13(1): 37–40. doi: 10.1080/09537100120104890.

15. Averkov OV. Acetylsalicylic acid as a drug: which drug forms are preferable from the standpoint of evidence-based medicine? Cardiovascular therapy and prevention. 2010; (2): 61–68. (In Russ).

16. Martynov AI, Gorokhovskaya GN, Avetyan NG, et al. Modern view of the position of acetylsalicylic acid in the prevention of thrombosis and embolism. Russian Journal of Cardiology. 2004; 3(47): 89–95. (In Russ).

17. Zyryanov SK, Butranova OI. Clinical and pharmacological substantiation of the variability of the antiplatelet response when using different dosage forms of acetylsalicylic acid. Consilium Medicum. 2017; 19(10): 105–112. (In Russ).

18. I-Chen Wu, Hui-Min Hsieh, Ming-Tsang Wu. A short-term risk–benefit analysis of occasional and regular use of low-dose aspirin in primary prevention of vascular diseases. BMJ Open. 2015 Jan 9; 5(1): 006694. doi: 10.1136/bmjopen-2014-006694.

19. Machilskaya OV. Factors determining adherence to the treatment of patients with arterial hypertension. Cardiology and cardiovascular surgery. 2016; (3): 55–65. (In Russ).

20. Rafalsky VV, Kricova AV, Baglikov AN. Features of the clinical pharmacology of acetylsalicylic acid as an antithrombotic drug. Cardiovascular therapy and prevention. 2009; 8(7): 1–6. (In Russ).

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

22. Cipollone F, Rocca B, Patrono C. Ciclooxygenase-2 expression and inhibition in atherothrombosis. Arterioscler Thromb Vasc Biol. 2004 Feb; 24(2): 246–55. doi: 10.1161/01.ATV.0000104005.92603.f2.

23. Grosser T, Fries S, Lawson JA, et al. 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.

24. Windecker S, Kolh P, Alfonso F, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2014 Oct 1; 35(37): 2541–619. doi: 10.1093/eurheartj/ehu278.

25. Mirzaev KB, Sychev DA, Andreev DA. Genetic bases of resistance to clopidogrel: current state of the problem. Russian Journal of Cardiology. 2015; (10): 92–98. (In Russ).

26. Dahabreh IJ, Moorthy D, Lamont JL, et al Testing of CYP2C19 Variants and Platrlet Reactivity for Guiding Antiplatelet Treatment. Agency for Healthcare Research and Quality (US); 2013 Sep.Report No.: 13-EHC117-EF.

27. Miedema MD, Duprez DA, Misialek JR, et al. Use of coronary artery calcium testing to guide aspirin utilization for primary prevention. Circ Cardiovasc Qual Outcomes. 2014 May; 7(3): 453-60. doi: 10.1161/CIRCOUTCOMES.113.000690.

28. Minushkina LO. Primary prevention of cardiovascular diseases and antiplatelet therapy.Medical Council. 2017; (7): 89–93. (In Russ).

29. MacDonald TM., Wei L. Effect of ibuprofen on cardioprotecive effect of aspirin. Lancet. 2003 Feb 15; 361(9357): 573–4. doi: 10.1016/s0140-6736(03)12509-3.

30. Martsevich SYu, Suvorov AYu. Combined use of clopidogrel and proton pump inhibitors. Rational Pharmacotherapy in Cardiology. 2014; 10(6): 665–671. (In Russ).

31. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA study. J Am Coll Cardiol. 2008 Jan 22; 51(3): 256-60. doi: 10.1016/j.jacc.2007.06.064.

32. Yano H, Tsukahara K, Morita S, et al. Influence of omeprazole and famotidine on the antiplatelet effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes. Circ J. 2012; 76(11): 2673–80. doi: 10.1253/circj.cj-12-0511.

33. Pulcinelli FM, Pignatelli P, Celestini A, et al. Inhibition of platelet aggregation by aspirin progressively decreases in long-term treated patients. Am Coll Cardiol. 2004 Mar 17; 43(6): 979–84. doi: 10.1016/j.jacc.2003.08.062.

34. Law WC, Gurbel PA, Watkins PB, et al. Atorvastatin reduces the ability of clopidogrel to inhibit plateletaggregation: a new drug-drug interaction. Circulation. 2003 Jan 7; 107(1): 32–7. doi: 10.1161/

35. Serebrunay VL, Gurbel PA, Alexander JH, et al. Statins do not affect platelet inhibition with clopidogrel during coronary stenting. Atherosclerosis. 2001 Nov; 159(1): 239-41. doi: 10.1016/s0021-9150(01)00606-2.

36. Mega JL, Simon T, Anderson J, et al. CYP2С19*2 Genetic Variants and Clinical Outcomes With Clopidogrel: Meta-Analysis. Circulation. 2009; 120: 598–9.

37. Ferguson AD, Dokainish H, Lakkis N. Aspirin and clopidogrel response variability: review of the published literature. Tex Heart Inst J. 2008; 35(3): 313–20.

38. Csiszar A, Stef G, Pacher P, et al. Oxidative stress-induced isoprostane formation may contribute to aspirin resistance in platelets. Prostaglandins Leukot Essent Fatty Acids. May-Jun 2002; 66(5–6): 557–8. doi: 10.1054/plef.2002.0399.

39. Gori AM, Marcucci R, Migliorini A, et al. Incidence and clinical impact of dual nonresponsiveness to aspirin and clopidogrel in patients with drug-eluting stents. J Am Coll Cardiol. 2008 Aug 26; 52(9): 734–9. doi: 10.1016/j.jacc.2008.05.032.

40. Knight CJ, Panesar M, Wilson DJ, et al. Different effect sofcalcium antagonists, nitrates, and beta-blocker sonplatelet function.Possible importance for the treatment of unstable angina. Circulation. 1997 Jan 7; 95(1): 125–32. doi: 10.1161/01.cir.95.1.125.

41. CURRENT-OASIS 7 Investigators. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010 Sep 2; 363(10): 930–42. doi: 10.1056/NEJMoa0909475.

42. Pearson TA, Blair SN, et al. AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patient without Coronary or other Atherosclerotic Vascular Diseases. Circulation. 2002 Jul 16; 106(3): 388–91. doi: 10.1161/01.cir.0000020190.45892.75.

43. Frolova NS, Shakhnovich RM, Kaznacheeva EM, et al. Resistance to aspirin. Cardiovascular therapy and prevention. 2010; 9(6): 40–46. (In Russ).

44. Shamir R Mehta, Jean-Pierre Bassand, Susan Chrolavicius, Rafael Diaz CURRENT-OASIS 7. Dose comparisons of clopidogrel and aspirin in acute coronary syndromes. N Engl J Med. 2010 Sep 2; 363(10): 930–42. doi: 10.1056/NEJMoa0909475.

45. Matthew J Price, Peter B Berger. Standard-vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA. 2011 Mar 16; 305(11): 1097–105. doi: 10.1001/jama.2011.290.

46. Valenti R, Marcucci R, Capodanno D. Residual platelet reactivity to predict long-term clinical outcomes after clopidogrel loading in patients with acute coronary syndromes (RECLOSE 2-ACS) study. J Thromb Thrombolysis. 2015 Jul; 40(1): 76–82. doi: 10.1007/s11239-014-1159-1.

47. Udell JA, Braunwald E, et al. Prasugrel versus clopidogrel in patients with ST-segment elevation myocardial infarction according to timing of percutaneous coronary intervention: a TRITON-TIMI 38. JACC Cardiovasc Interv. 2014 Jun; 7(6): 604–12. doi: 10.1016/j.jcin.2014.01.160.

48. Dunn SP, Steinhubl SR, et al. Impact of proton pump inhibitor therapy on the efficacy of clopidogrel in the CAPRIE and CREDO trials. J Am Heart Assoc. 2013 Jan 15; 2(1): 004564. doi: 10.1161/JAHA.112.004564.

49. Valgimigli M, Bueno H, Byrne RA, et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS. Eur Heart J. 2018 Jan 14; 39(3): 213–260. doi: 10.1093/eurheartj/ehx419.

50. Yusuf S, Zhao F, Mehta SR, et al.Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. The CURE study. N Engl J Med. 2001 Aug 16; 345(7): 494–502. doi: 10.1056/NEJMoa010746.

For citation

Salukhov V.V., Gulayev N.I., Chepel A.I., Zemlyanoy A.B., Dorokhina E.V. Preventive antiplatelet therapy of ischemic heart disease complications in conditions of variability of platelet response. Bulletin of Pirogov National Medical & Surgical Center. 2020;4(15):82-90. (In Russ.)