Rational Pharmacotherapy in Cardiology

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Antiplatelet agents are a necessary component of modern atherosclerosis therapy. The difficulties of antiplatelet treatment lie in the balance between the necessary therapeutic effect of the drug and the risk of excessive action leading to the bleeding. Possibility to control pharmacodynamics effects of antiplatelet agents is still very limited. Pharmacology of antiplatelet drugs is growing rapidly. Some of new antiplatelet drugs are on their way to clinical application — prasugrel, ticagrelor, elinogrel, inhibitors of thromboxane and thrombin receptors. Clinical pharmacology of these drugs is different. This requires a doctor's good knowledge of their identity to avoid the development of iatrogenic complications.

About the Author

A. B. Sumarokov
Institute for Cardiology named after A.L. Mjasnikov, Russian Cardiology Research and Production Complex
Russian Federation


1. Wang Shah., Bhatt D.L., Topol E.J. Aspirin and clopidogrel resistance: an emerging clinical entity. Eur Heart J 2006;27:647-654.

2. Spertus J.A., Kettelkamp R., Decker C. et al. Prevalence, Predictors, and Outcomes of Premature Discontinuation of Thienopiridine Therapy After Drug-Eluting Stent Placement. Results From the Premier Registry. Circulation 2006;113(24):2803-2809.

3. Moukarbel G.V., Signorovitch J.E., Pfeffer M.A. et al. Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial. Eur Heart J 2009;30:2226-2232.

4. Collet J.P., Hulot J.S., Pena A. et al. Cytochrome P450 2C19 polymorphism in young patients, treated with clopidogrel after myocardial infarction: a cohort study. Lancet, 2009, V 373, 309-317.

5. Simon T, Verstuyft C, Mary-Crause M, Quteinch L, Drouet E, Meneveau N, Steg PG, Ferriers J, Danchin N, Becquemont L. Genetic determinants of response to clopidogrel and cardiovascular events. N En-glJMed 2009;360:363-375.

6. Mega J.L., Close S.L., Wiwiott S.D. et al. Cytochrome P-450 polymorphism and response to clopidogrel. N EnglJMed 2009;360:354-362.

7. Sugidachi A., Asai F., Yoneda K. et al. Antiplatelet action of R-99224, an active metabolite of a novel thienopyridine-type Gi-linked P2T antagonist, CS-747. British J of Pharmacology 2001; 132: 47-54.

8. Brandt J.T., Close S.L., Iturria S.J. et al, Common polimorphism of CYP 2C19 and CYP2C29 affect the pharmacokinetics of and pharmacodynamic of response to clopidogrel but not to prasugrel. J Thromb Haemost 2007;5(12):2429-2436.

9. Matsushima N., Jakubovsky J.A., Asai F. et al. Platelet inhibitory activity and pharmacokinetic of prasugrel (CS -747) a novel thienopyridine P2Y12 inhibitor: a multiple-dose study in healthy subjects. Platelets 2006, 17(4): 218-226.

10. Jernberg T., Payne C.D., Winters K.J. et al. Prasugrel achives greater inhibition of platelet aggregation and a lower rate of non-responders compared to clopidogrel in aspirin treated patients with stable coronary artery disease. Eur Heart J 2006; 27: 1166-1173.

11. Weerakkody G.J., Jakubowski J.A., Brandt J.T. et al. Greater inhibition of platelet aggregation and reduced response variability with prasugrel versus clopidogrel: an integrated analysis. J Cardiovasc Pharmacol Ther 2007;12(3):205-12.

12. Payne C.D., Grace Y., Small D.S. et al. Encreased Active Metabolite Formation Explains the Greater Platelet Inhibition With Prasugrel Comparedti High Dose Clopidogrel. J Cardiovasc Pharmacol 2007;50(5):555-562.

13. NiitsuY., Jakubowski J.A., Sigudashi A. et al. Pharmacology of CS747 (prasugrel, LY640315), a novel, potent antiplatelet agent within vivo P2Y12 receptor antagonist activity. Semin Thromb Haemosta-sis 2005;31:184-194.

14. Wiwiott S.D., Braunvald E., McCabe C.H. et al, for the TRITON –TIMI 38 Investigators. Prasugrel versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2007;359(20):2001-2015.

15. Wiwiott S.D., Antman E.M., Winters K.J. et al, for JUMBO-TIMI 26 Investigatiors Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation 2005;111(1):3366-3373.

16. Wiwiott S.D., Trenk D., Frelinger A.L. et al, for the PRINCIPLE-TIMI 44 Investigators. Prasugrel Compared With High Loading- and Maintence-Dose Clopidogrel in Patients With Planned Percutaneous Coronary Intervention. The Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation — Thrombolysis in Myocardial Infarction 44 Trial. Circulation 2007;116:2923-2932.

17. Jakubowski J.A., Mastushima N., Asai F. et al. A multiple dose study of prasugrel (CS-747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans. Br J Clin Pharmacol 2007;63(4):421-430.

18. Wallentin L., Varenhorst C., James S. et al. Prasugrel achives greater and faster P2Y12 receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin treated patients with coronary artery disease. Eur Heart J 2008;29(1):21-31.

19. Antman E.M., Wiwiott S.D., Murphy S. et al. Early and Late Benefits of Prasugrel in Patients With Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: A TRITON –TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimazing Platelet Inhibition with Prasugrel- Thrombolysis in Myocardial Infarction ) Analysis. JACC 2008;51(21):2028-2033

20. Pride Y.B., Wiwiott S.D., Buros J.L. et al, TIMI Study Group. Effect of prasugrel versus clopidogrel on outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention without stent implantation: a Trial to assess Improvement in Therapeutic Outcomes by opti-mazing platelet inhibitioN with prasugrel (TRITON) — Thrombolysis in Myocardial Infarction (TIMI) 38 substudy. Am Heart J 2009;158(3):21-26.

21. Serebruany V.L. Platelet inhibition with prasugrel and cancer risk: potential causes and implications. Am J Med 2009;122(5):407-8.

22. Bhatt D. Prasugrel in Clinical Practice. N Engl J Med 2009;361(10):940-942

23. Weerakkody G., Jakubovsky J.A., Brandt J.T. et al. Comparison ofspeed of oncet of platelet inhibition after loading doses of clopidogrel versus prasugrel in healthy volunteers and correlation with responder status. Am J Cardiol 2007;100(2):331-336.

24. Serebruany V.L., Midei M.G., Meilman H. et al. Platelet inhibition with prasugrel (CS-747) compared with clopidogrel in patients undergoing coronary stenting: the subset from the JUMBO study. Post-grad Med J 2006;82(3):404-410.

25. Michelson A.D., Frelinger A.L., Braunwald E. et al, for the TRITON- TIMI 38 Investigators. Pharmacodynamic assessment of platelet inhibition by prasugrel vs. Clopidogrel in the TRITON- TIMI 38 trial. Eur Heart J 2009;30:1753- 1763.

26. Wiviott S.D., Trenk D., Frelinger A.L. et al, for the PRINCIPLE –TIMI 44 Investigators. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: the Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 2007;116(25):2923-2932.

27. Rehme J.L., Eckstein J.A., Farid N.A. et al. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent with cytochrome P450. Drug Metab Dispos 2006; 34: 600-607.

28. Montalescot G., Sideris G., Cohen R. et al. Prasugrel compared with high dose clopidogrel in acute coronary syndrom. The randomized, double blind ACAPULCO study. Thromb Haemostas 2010;103(1):210-223.

29. Harker L.A., Boissel J.P., Pilgrim A.J., Gent M. Comparative safety and tolerability of clopidogrel and aspirin: results from CAPRIE. CAPRIE Steering Committee and Investigators. Clopidogrel versus aspirin in patients at risk of ischaemic events. Drug Saf 1999;21(4):325-35.

30. Ruland S. Safety of clopidogrel and aspirin for stroke prevention: implications of the CHARISMA trial. Drug Saf 2008;31(6):449-58.

31. Ho M.P., Peterson E.D., Wang L et al. Incidence of Death and Acute Myocardial Infarction Associated With Stopping Clopidogrel After Acute Coronary Syndrome. JAMA 2008; 299(5):532-539.

32. McFadden E.P., Stabile E., Regar E. et al. Late thrombosis in Drug-Eluting Coronary Stents discontinuation of antiplatelet therapy. Lancet 2004; 364: 1519-1521.

33. Schulz S., Schuster T., Mehili J. et al. Stent thrombosis after drug-eluting stent implantation: incidence, timing, and relation to discontinuation of clopidogrel therapy over a 4-year period. Eur Heart J 2009;30(32):2714-2721.

34. Grines C.L., Bonow R.O., Casey D.E. Jr. 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 College of Physicians. Circulation 2007;115:813-818.

35. Serebruany V.L., Midei M.G., Melman H. et al. Rebound platelet activation after termination of prasugrel and aspirin therapy due to confirmed non-compliance in patient enrolled in the JUMBO Trial. Intern J Clin Practice 2008;60(7):863-866.

36. Sibbing D., Stegger J., Braun S. et al. A Double-Blind, Randomized Study on Prevention and Exestence of a Rebound Phenomenon of Platelets After Cessation of Clopidogrel Treatment. JACC 2010;55(6):558-565.

37. Angiolillo D.J., Bernardo E., Sabate M et al. Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. JACC 2007;50(19):1541-1547.

38. Erlinge D., Varenhorst C., Braun O.O. et al. Patients With Poor Responsiveness to thienopyridine treatment or With Diabetes Have Lower Levels of Circulating Active Metabolite, but Their Platelets Respond Normally to Active Metabolite Added Ex Vivo. JACC 2008;52(24): 1968-1977.

39. Chin C.T., Roe M.T., Fox K.A. et al. Study design and rationale of a comparison of prasugrel and clopidogrel in medically managed patients with unstable angina/non-ST-segment elevation myocardial infarction: the TaRgeted platelet Inhibition to cLarify the Optimal strateGy to medicallY manage Acute Coronary Syndromes (TRILOGY ACS) trial. Am Heart J 2010;160(1):16-22.e1

40. Wiwiott S.D., Braunwald E., Angiolillo D.J. et al, for the TRITON-TIMI38 Investigators. GreaterClini-cal Benefit of More Intencive Oral Antiplatelet Therapy With Prasugrel in Patients With Diabetes Mellitus in the Trial to Assess Improvement in Therapeutic Outcomes by Optimazing Platelet Inhibition With Prasugrel — Thrombolysis in Myocardial Infarction 38. Circulation 2008;118:1626-1636.

For citation:

Sumarokov A.B. NEW ANTIPLATELET DRUGS (PART 1). Rational Pharmacotherapy in Cardiology. 2011;7(1):82-88. (In Russ.)

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