Difficulties in evaluating the efficacy of antiplatelet therapy in clinical practice


Aim. To evaluate platelet activity changes in patients with coronary artery disease (CAD) treated with aspirin, clopidogrel and combination of these drugs; to estimate the rate of resistance of CAD patients to antiplatelet treatment.
Material and methods. 199 patients with stable CAD were included in the study. Of them, 83 were given aspirin, 46 received clopidogrel, 34 - double antiplatelet therapy (both aspirin and clopidogrel). The trial also studied an additional group of 18 CAD patients on double antiplatelet therapy who had hemorrhages. The control group consisted of 25 healthy volunteers. Platelet aggregation was measured both by a mean size of aggregates (MSA) and light transmission (LTM, Born method) using BIOLA platelet aggregation analyzer. A platelet shape, leukocyte-platelet aggregates (LPA) and erythrocyte-platelet aggregates (EPA) in the whole blood were studied using scanning electron microscopy. The levels of IL-6 and sVCAM were also measured.
Results. It was found that 59.8% patients with CAD had high platelet reactivity revealed in 94.9% of cases by measuring spontaneous and induced by 0.1 mcM ADP platelet aggregation. LTM revealed increased platelet reactivity only in 10.7% patients. Resistance to aspirin correlated with the presence of LTA (r = 0.629, p = 0.0001) and the number of large "reticulated" platelets (r = 0.334, p = 0.001). Low platelet reactivity was associated with the presence of circulating EPA (r = -0.362, p = 0.008). Administration of clopidogrel did not decrease platelet reactivity to normal levels in 34.7% patients which correlated with the presence of LPA and EPA. In 83.3% patients with hemorrhages platelet aggregation, induced by 5.0 mcM, ADP was dramatically decreased.
Conclusion. Resistance to antiplatelet therapy is related to platelet heterogeneity, the presence of inflammation and state of erythrocytes. LT is capable to reveal only a part of patients resistant to antiplatelet drugs. To fully identify these patients, it is necessary to register spontaneous platelet aggregation and aggregation induced by low doses of ADP. Redundant inhibition of platelet reactivity could be the cause of hemorrhagic events.


  1. Sabatine M., Cannon C., Gibson C. et al. CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N. Engl. J. Med. 2005; 352(12): 1179-1189.
  2. Yusuf S., Zhao F., Mehta S. R. et al. Effect of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N. Engl. J. Med. 2001; 345: 494-502.
  3. Becker R., Meade T., Berger P. et al. The primary and secondary prevention of coronary heart disease: American College of Chest Physicians Evidence. Based Clinical Practice Guidelines (8-th Edition). Chest 2008; 133 (6, Suppl.): 776S-814S.
  4. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high-risk patients. Br. Med. J. 2002; 324: 71-86.
  5. Dunning J., Versteegh M., Fabbri A. et al. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur. J. Cardiothorac. Surg. 2008; 34: 73-92.
  6. Steinhubl S., Berger P., Mann J. et al. Clopidogrel for the reduction of events during observation: early and sustained dual oral antiplatelet therapy following percutaneous intervention: a randomized controlled trial. J. A. M. A. 2002; 288(19): 2411-2420.
  7. Jackson M., Glagett G. Antithrombotic therapy in peripheral arterial occlusive disease. Chest 2001; 119: 283S-299S.
  8. Serebruany V., Malinin A., Ferguson J. et al. Bleeding risks of combination vs. single antiplatelet therapy: a meta-analysis of 18 randomized trials comprising 129 314 patients. Fundament. Clin. Pharmacol. 2008; 22(3): 315-321.
  9. Ng F., Wong S., Lam K. et al. Gastrointestinal bleeding in patients receiving a combination of aspirin, clopidogrel, and enoxaparin in acute coronary syndrome. Am. J. Gastroenterol. 2008; 103(4): 865-871.
  10. Ермакова О. В., Кучерявая Н. Г., Кокурина Е. В. и др. Антиагрегантная эффективность и переносимость новой буккальной и пероральной кишечно-растворимой формы ацетилсалициловой кислоты. Профилакт. забол. и укреп. здоровья. 2008; 5: 35-39.
  11. Iso H., Hennekens C., Stampfer M. et al. Prospective study of aspirin use and risk of stroke in women. Stroke 1999; 30(9): 1764-1771.
  12. Grines C., Bonow R., Casey D. et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation 2007; 115(6): 813-818.
  13. Ferrari E., Benhamou M., Cerboni P. Coronary syndromes following aspirin withdrawal: a special risk for late stent thrombosis: J. Am. Coll. Cardiol. 2005; 45: 456-459.
  14. Ho P., Peterson E., Wang L. et al. Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. J. A. M. A. 2008; 299(5): 532-539.
  15. Meadows T., Bhatt D. Clinical aspects of platelet inhibitors and thrombus formation. Circ. Res. 2007; 100: 1261-1275.
  16. Gurbel P. The relationship of platelet reactivity to the occurrence of poststenting ischemic events: emergence of a new cardiovascular risk factor. Rev. Cardiovasc. Med. 2006; 7(suppl. 4): S20-S28.
  17. Matetzky S., Shenkman B., Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004; 109: 3171-3175.
  18. Gum P., Kottke-Marchant K., Welsh P. 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): 961-965.
  19. Angiolillo D., Bernardo E., Sabatй M. et al. Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. J. Am. Coll. Cardiol. 2007; 50(16): 1541-1547.
  20. Helgason C., Bolin K., Hoff J. et al. Development of aspirin resistance in persons with previous ischemic stroke. Stroke 1994; 25: 2331-2336.
  21. Bliden K., DiChiara J., Tantry U. et al. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate? J. Am. Coll. Cardiol. 2007; 49(6): 657-666.
  22. Michelson A., Cattaneo M., Eikelboom J. et al. Aspirin resistance: position paper of the Working Group on Aspirin Resistance. J. Thromb. Haemost. 2005; 3: l309-1311.
  23. Krasopoulos G., Brister S., Beattie W. Aspirin "resistance" and risk of cardiovascular morbidity: systematic review and meta-analysis. Br. Med. J. 2008; 336: 195-198.
  24. Geisler G., Kapp M., Gцhring-Frischholz K. et al. Residual platelet activity is increased in clopidogrel and ASA-treated patients with coronary stenting for acute coronary syndromes compared with stable coronary artery disease. Heart 2008; 94: 743-747.
  25. Bonello L., Camoin-Jau L., Argues S. et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J. Am. Coll. Cardiol. 2008; 51(14): 1404-1411.
  26. Toshima H., Sugihara H., Hamano H. et al. Spontaneous platelet aggregation in normal subject assessed by a laser light scattering method: An attempt at standardization. Platelets 2008; 19(4): 293-299.
  27. Frelinger A., Li Y., Linden M. et al. Lack of association between cyclooxygenase-1-dependent platelet function assays and adverse clinical outcomes in 700 consecutive aspirin-treated patients presenting for cardiac catheterization. J. Am. Coll. Cardiol. 2008; 51: A370.
  28. Pamukcu B., Oflaz H., Onur I. et al. Clinical relevance of aspirin resistance in patients with stable coronary artery disease: a prospective follow-up study (PROSPECTAR). Blood Coagul. Fibrinolys. 2007; 18(2): 187-192.
  29. Christiaens L., Macchi L. Monitoring of the antiplatelet drugs effect in patients with coronary artery disease: what is the real clinical impact? Curr. Vasc. Pharmacol. 2007; 5(4): 293-301.
  30. Trip R., Cats V., van Capelle F. Platelet hyperactivity and prognosis of survivors of myocardial infarction. N. Engl. J. Med. 1990; 323: 1549-1554.
  31. Kajiwara I., Ogawa H., Soejima H. et al. The prognostic value of small-sized platelet aggregates in unstable angina: detection by a novel laser-light scattering method. Thromb. Res. 2001; 101(3): 109-118.
  32. Iwase E., Tawata M., Aida K. et al. A cross-sectional evaluation of spontaneous platelet aggregation in relation to complications in patients with type II diabetes mellitus. Metabolism 1998; 47: 699-705.
  33. Breddin H., Lippold R., Bittner M. et al. Spontaneous platelet aggregation a predictive risk factor on vascular occlusions in healthy volunteers? Results of the HAPARG Study. Haemostatic parameters as risk factors in healthy volunteers. Atherosclerosis 1990; 144: 211-219.
  34. Nakonechnicov S., Gabbasov Z., Chazova I. et al. Platelet aggregation in patients with primary pulmonary hypertension. Blood Coagul. Fibrinolys. 1996; 7(2): 225-227.
  35. Скворцов А., Габбасов З., Попов Е. и др. Новый подход к исследованию агрегации тромбоцитов больных ДКМП. Тер. арх. 1989; 61(2): 95-97.
  36. Ho M., Peterson E., Wang L. et al. Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. J. A. M. A. 2008; 299(5): 532-539.



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