Rational Pharmacotherapy in Cardiology

Advanced search


Full Text:


Antiplatelet agents are a necessary component of modern therapy of atherosclerosis. The difficulties of the antiplatelet treatment lie in balance between the necessary therapeutic effect and the risk of excessive action, leads to the bleeding. The ability to monitor antiplatelet pharmacodynamics is still very limited. Pharmacology of antiplatelet drug has been developing rapidly. New antiplatelet drugs are on their way to clinical application — prasugrel, ticagrelor , elinogrel, thromboxane receptor inhibitors, thrombin receptors inhibitors. Clinical pharmacology of these drugs is different. Practitioner should know their specifics 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. Leonardi S., Rao S.V., Harrington R.A. et al. Rationale and design of the randomized, double-blind trial testing INtraveNous and Oral administration of elinogrel, a selective and reversible P2Y(12)-receptor inhibitor , versus clopidogrel to eVAluate Tolerability and Efficacy in nonurgent Percutaneous Coronary Interventions patients (INNOVATE-PCI). Am Heart J 2010;160(1):65-72.

2. Berger J.S., Roe M..T, Gibson C.M. et al. Safety and feasibility of adjuvanctive antiplatelet therapy with elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the Early Rapid ReversAL of platelet thrombosis with intravenous Elinogrel before PCI to optimaze reperfusion in acute Myocardial Infarction (ERASE MI) pilot trial. Am Heart J 2009; 158(6): 998-1004.

3. Husted S., Emanuelsson H., Heptinstall S. et al. Pharmacodynamiks, pharmacokinetics, andsafaty of the oral reversible P2Y12 antagonist AZD 6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 2006;27(11):1038-1047.

4. Gurbel P ., Blinden K.P ., Butler K. et al. Randomized Double-Blind Assesment of the ONSET and OFF-SET of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Stable Coronary Artery Disease. The ONSET/ OFFSET Study. Circulation 2009; 120: 2577-2585.

5. Kastrati A., Ndrepera G. Cangrelor — A Champion Lost in Translation? N Engl J Med 2009; 361(24): 2382-2384

6. Dovlatova N.L., Jakubovsky J.A., Sugidashi A., Heptinstall S. The reversible P2Y12 antagonist cangrelor influences the ability of the active metabolites of clopidogrel and prasugrel to produce irreversible inhibition of platelet function. J Thromb Haemost 2008;6(7): 1153-1159.

7. Oestereich J.H. Elinogrel, a reversible P2Y12receptor antagonist for the treatment of acute coronary syndrome and prevention of secondary thrombotic events. Curr Opin Invest Drugs 2010; 11(3): 340-348.

8. Bhatt D.L., Lincoff A.M., Gibson C.M. et al. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009;361(24):2330-41

9. Gurbel P .A., Bliden K.P ., Antonino M.J. et al. The effect of elinogrel on high platelet reactivity during dual antiplatelet therapy and the relation to cyp 2c19*2 genotype: first experiancein patients. J Thromb Haemost 2009; 8(1): 43-53.

10. Butler K., T eng R. Pharmakokinetics, pharmakodinamics and safety and tolerability of multiple ascending doses of tikagrelor in healthy volunteers. Br J Clin Pharmacol 2010; 70(1): 65-77.

11. Husted S., Emanuelsson H., Heptinstail S. et al, Pharmakodinamics, pharmakokinetics and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a dou- ble-blind comparison to clopidogrel with aspirin. Eur Heart J 2006; 27(11): 1038-1047.

12. Gurbel P ., Bliden K.P ., Butler K. et al. Randomized Double-Blind Assesment of the ONCET and OFF-SET of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in Patients With Stable Coronary Artery Disease. The ONCET / OFFSET Study. Circulation 2009; 120: 2577-2585.

13. Cannon C.P ., Harrington R.A., James S. et al, for PLATO investigators. Comparison of ticagrelor with clopidogrel in patients with a planned invasive stategy for acute coronary syndromes (PLATO): a ran- domized double-blind study. Lancet 2010; 375: 283-293.

14. Cannon C.P ., Husted S., Harrington R.A. et al, for the DISPERSE-2 Investigators. Safety , Tolerability , and Initial Efficacy of AZD6140, the first Reversible Oral Adenosine Diphosphate Receptor Antagonist, Compared With Clopidogrel, in PatientsWith Non-ST-Segment Elevation Acute Coronary Syndrome. Primary Results of the Disperse-2Trial. N Engl J Med 2009; 50(19): 1844-1851.

15. Storey R.F ., Blinden K., Patil S.B. et al. The Effect ofTicagrelor on Cardiopulmonary Function in Patients With Stable Coronary Artery Disease. Circulation 2009; 120 Suppl: S1145.

16. Serebruany V.L., Stebbing J., Atar D. Dyspnoe after antiplatelet agents: the AZD6140 controversy. Int J Clin Pract 2007; 61(3): 529-533.

17. Wallentin L., Becker R.C., Budaj A. et al, for the Plato Investigators. Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. N Engl J Med 2009;361(11): 1045-1057.

18. Stone GW. Ticagrelor in ACS: redefining a new standart of care? Lancet 2010;375(9711): 263-266.

19. Gurbel P .A., Bliden K., Butler K. et al. Response to Tikagrelor in Clopidogrel Nonresponders and Re- sponders and Effect of Swithching Therapies: The RESPOND Study . Circulation 2010; 121: 1188-1199.

20. Serebruany V .L. The TRITON versus PLATO trials: Differences beyond platelet inhibition. Thromb Haemost 2010; 103(2): 1-3.

21. Gaussem P ., Reny J.L., Thalamus C. et al. The specific thromboxan receptor antagonist S18886: phar- macokinetic pharmacodynamic studies. J Thromb Haemost 2005;3: 1437-1445.

22. Viles-Gonsales J.F ., Fuster V., Corti R. et al. Atherosclerosis regression and ATP receptor inhibition: effect of S18886 on plaque size and composition — a magnetic resonance imaging study. Eur Heart J 2005; 26(15):1557-1561.

23. Belhaussen L., Pelle G., Dubois-Rande J.-L. et al. Improved endothelial function by thromboxan A2 receptor antagonist S18886 in patients with coronary artery disease treated with aspirin. JACC 2003;41: 1198-1204.

24. Sebekova K., Eifert T., Klassen A. et al. Renal Effect of S18886 (Terutroban), a TP Receptor Antagonist, in an Experimental Model of Type 2 Diabetes. Diabetes 2007; 56(4): 968-974.

25. Sollier B.D.C., Crassard I., Simoneau G. et al. Effect of the thromboxane prostaglandine receptor antagonist terutroban on arterial thrombogenesis after repeated administration in patients treated for the prevention of ischemic stroke. Cerebrovasc Dis 2009; 28(5): 505-513.

26. Henerici M.G. Rationale and Desain of the Prevention and Cardiovascular Events of Ischemic Origin with Terutroban in Patients with a History of Ischemic Stroke or Transient Ischemic Stroke or Transient Ischemic Attack (PERFORM ) Study. Cerebrovasc Disease 2009; Suppl 3: 28-32.

27. Strukova S.M. Blood coagulation-dependent inflammation. Coagulation- dependen inflammation and inflammation — dependent thrombosis. Front Biosci 2006; 11: 59-80.

28. Coughlin S.R. Protease activated receptors in haemostasis, thrombosis and vascular biology. J Thromb Haemost 2005;3: 1800-1814.

29. Chintala M., Shimuzu K., Ogawa M. et al. Basic and translational research on protease-activated re- ceptors: antagonism of the protease-activated receptor 1 for thrombin, a novel approach to antiplatelet therapy for atherosthrombotic disease. J Pharmacol Sci 2008;108(4): 433-438.

30. Kosoglou T., Reyderman L., Robert R. et al. Pharmacodynamics and pharmacokinetics of novel protease-activated receptor (PAR-1) antagonist SCH530348. Circulation 2005; 112 (Suppl): I-32.

31. Becker R.C., Moliterno D.J., Jennings L.K. et al, for the TRA-PCI Investigators. Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary interventions: a randomized, double-blind, placebo-controlled phase II study. Lancet 2009;373(9667): 919-928.

32. Siller-Matula J.M., Krumphuber J., Jilma B. Pharmacokinetic, pharmacodynamic and clinical profile of novel antiplatelet drugs targeting vascular diseases. Br J Pharmacol 2010; 159(3): 502-517.

33. Serebruany V.L., Kogushi M., Dastros–Pitei D. et al. The in-vitro effects oe E5555, a protease-activated receptor (PAR)-1 antagonist, on platelet biomarkers in healthy volunters and patients with coronary artery disease. Thromb Haemost 2009; 102(1): 111-119.

34. Angiolillo D.J., Capodano D., Goto S. Platelet thrombin receptor antagonism and thrombosis. Eur Heart J 2010;31:17-28.

For citation:

Sumarokov A.B. NEW ANTIPLATELET DRUGS. PART 2. Rational Pharmacotherapy in Cardiology. 2011;7(5):637-643. (In Russ.)

Views: 315

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)