Rational Pharmacotherapy in Cardiology

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Aim. To evaluate risk of repeated atherothrombotic events in patients survived acute coronary syndrome (ACS) and having poorly reduced platelet aggregation (proven by optical aggregometry) in response to acetylsalicylic acid (ASA) therapy.

Material and methods. 200 patients with ACS (aged 56,6±9,2 y.o.) were included in the study. Platelet functional activity during ASA therapy was evaluated with laser aggregometer. ASA resistance was defined if the summarizing index of platelet aggregation (induced with ADP, 5 mμml/l) was 50% or higher during ASA therapy. Observation period was 18±6 months. Atherothrombotic events (unstable angina, myocardial infarction, stroke, cardiovascular death) were considered.

Results. Lack ASA response rate was about 12%. Totally 22 repeated atherothrombotic events were registered: 5,6% among ASA sensitive patients and 50% - among ASA resistant patients. Repeated atherothrombotic events were registered in ASA resistance patients during first 14 days. ASA sensitive patients showed repeated atherothrombotic events in some months after ACS. The relative risk of cardiovascular event in ASA resistance patients was 8,92 (CI 95% 4,39; 17,84 р=0,05).

Conclusion. The high level of the induced platelet aggregation (proven by laser aggregometry) points to high risk of repeated atherothrombotic events in patients with ACS.

About the Authors

N. F. Puchinyan
Saratov Research Institute for Cardiology
Russian Federation
Chernyshevskogo ul. 141, Saratov, 410028

N. V. Furman
Saratov Research Institute for Cardiology
Russian Federation
Chernyshevskogo ul. 141, Saratov, 410028

A. R. Kiselev
Saratov Research Institute for Cardiology
Russian Federation
Chernyshevskogo ul. 141, Saratov, 410028

Ya. P. Dovgalevsky
Saratov Research Institute for Cardiology
Russian Federation
Chernyshevskogo ul. 141, Saratov, 410028


1. 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.

2. Antithrombotic 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(7329):71–86.

3. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 1988;2(8607):349–60.

4. Patrono C., Bachmann F., Baigent C. et al. Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology. Eur Heart J 2004;25(2):166-81.

5. MichelsonA.D., Cattaneo M,. Eikelboom J.W. et al.Aspirin resistance: position paper ofthe Working Group on Aspirin Resistance. J Thromb Haemost 2005;3(6):1309–11.

6. Kumar A., Kao J. Platelet resistance to antiplatelet drugs. Recent Pat Cardiovasc Drug Discov 2009;4(2):98-108.

7. Mason P.J., Jacobs A.K., Freedman J.E. Aspirin Resistance and Atherothrombotic Disease. J Am Coll Car￾diol 2005;46(6):986–93.

8. Wang T.H., Bhatt D.L., Topol E.J. Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 2006;27(6):647-54.

9. Serebruany V.L., Steinhubl S.R., Berger P.B. et al. Variability in plateletresponsiveness to clopidogrel among 544 individuals. J Am Coll Cardiol 2005;45(2):246-51.

10. Kuliczkowski W., WitkowskiA., 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):426-35.

11. Bhatt D.L., Topol E.J. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov 2003;2(1):15-28.

12. Lordkipanidzé M., Pharand C., Nguyen T.A. et al. Comparison of fourtests to assess inhibition of platelet function by clopidogrel in stable coronary artery disease patients. Eur Heart J 2008;29(23):2877-85.

13. Eikelboom J.W., Hirsh J., Weitz J.I. et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002;105(14):1650-5.

14. Ang L., Mahmud E. Monitoring oral antiplatelet therapy: is it justified? Ther Adv Cardiovasc Dis 2008;2(6):485-96.

15. MichelsonA.D. Plateletfunction testing in cardiovascular diseases. Circulation 2004;110(19):e489-93.

16. Ушкалова Е.А. Аспиринорезистентность: механизмы развития, методы определения и клиническое значение. Фарматека 2006;(13):35-41.

17. Gum P.A., Kottke-Marchant K., Poggio E.D. et al. Profile and prevalence of aspirin resistance in patients with cardiovascular disease. Am J Cardiol 2001;88(3):230-5.

18. Gum P.A., Kottke-Marchant K., Welsh P.A. et al. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003;41(6):961-5.

19. Grundmann K., Jaschonek K., Kleine B. et al. Aspirin non-responder status in patients with recurrent cerebral ischemic attacks. J Neurol 2003;250(1):63-6.

20. Chen W.H., Lee P.Y., Ng W. et al. Aspirin resistance is associated with a high incidence of myonecrosis after non-urgent percutaneous coronary intervention despite clopidogrel pretreatment. J Am Coll Cardiol 2004;43(6):1122-6.

21. Nguyen T.A., Diodati J.G., Pharand C. Resistance to clopidogrel: a review of the evidence. J Am Coll Cardiol 2005;45(8):1157-64.

22. Wiviott S.D., Antman E.M. Clopidogrel resistance: a new chapter in a fast-moving story. Circulation 2004;109(25):3064-7.

23. BarskyA.A.,AroraR.R.Clopidogrelresistance:mythorreality? JCardiovasc Pharmaco l Ther2006; 11(1): 47-53.

24. Michelson A.D., Frelinger A.L. 3rd, Furman M.I. Current options in platelet function testing. Am J Cardiol 2006;98(10A):4N-10N.

25. Gurbel P.A., Becker R.C., Mann K.G. et al. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 2007;50(19):1822-34.

26. Бурячковская Л.И., Учитель И.А., Сумароков А.В., и др. Проблемы оценки эффективности дезагрегантной терапии в клинической практике. Тер арх. 2009;81(5):41-7.

27. Баркаган З.С., МомотА.П. Основыдиагностики нарушений гемостаза. М.: Ньюдиамед-АО; 1999.

28. Guidelines on plateletfunction testing. The British Society forHaematology BCSH Haemostasis and Thrombosis Task Force. J Clin Pathol 1988;41(12):1322-30.

29. Берковский А.Л., Васильев С.А., Жердеева Л.В. и др. Пособие по изучению адгезивно-агрегационной активности тромбоцитов. М.: НПО РЕНАМ; 2002.

30. Айнетдинова Д.Х., Удовиченко А.Е., Сулимов В.А. Резистентность к антитромбоцитарным препаратам у больных с острым коронарным синдромом без подъема сегмента ST. Кардиология 2008;48(6):35-9.

31. Berger P.B. Resistance to antiplatelet drugs: is it real or relevant? Catheter Cardiovasc Interv 2004;62(1):43-5.

32. Bhatt D.L. Resisting the temptation to oversimplify antiplatelet resistance. JACC Cardiovasc Interv 2008;1(6):660-2.

33. Patrono C., Rocca B. Aspirin: promise and resistance in the new millennium. Arterioscler Thromb Vasc Biol 2008;28(3):s25-32.

34. Гринштейн Ю.И., Савченко А.А., Гринштейн И.Ю. и др. Особенности гемостаза, метаболической активности тромбоцитов и частота резистентности к аспирину у больных с хронической сердечной недостаточностью после аортокоронарного шунтирования. Кардиология 2008;48(6):51-6.

35. Сироткина О.В., Богданова Е.В., Боганькова Н.А. и др. Эффективность антиагрегантной тера- пии клопидогрелом у пациентов, перенесших инфаркт миокарда с подъемом сегмента ST. Кардиоваскулярная терапия и профилактика 2009;8(1):51-5.

36. Рахимова Р.А., Аляви Б.А., Кенжаев М.Л., Давлатова Л.Ш. Влияние терапии клопидогрелом на показатели клеточного звена системы гемостаза при остром коронарном синдроме. Российский кардиологический журнал 2008;(6):33-7.

37. Пучиньян Н.Ф., Довгалевский П.Я., Фурман Н.В. Резистентность к ацетилсалициловой кислоте и частота развития тромботических событий у больных стабильной стенокардией. Рациональная Фармакотерапия в Кардиологии 2007;3(4):11-4.

38. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group. Lancet 1990;336(8719):827-30.

39. Marcucci R., Gori A.M., Paniccia R. et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation 2009;119(2):237-42.

40. Волков В.И., Рябуха В.В., Запровальная О.Е. Диагностика резистентности к аспирину у больных с ишемической болезнью сердца. Украинский кардиологический журнал 2006;(3):36-40.

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