#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

New players on the antiplatelet therapy chequerboard – what can we expect?


Authors: J. Bultas;  D. Karetová
Authors‘ workplace: Ústav farmakologie, 3. LF UK Praha, II. interní klinika kardiologie a angiologie, 1. LF UK Praha
Published in: Kardiol Rev Int Med 2010, 12(1): 38-45

Overview

Antithrombotic therapy plays an important role in the prophylaxis of cardiovascular diseases. Over the recent years, we have been witnessing an arrival of new antiplatelet therapies. A number of new antibody‑based molecules inhibiting thrombocyte adhesion are at the stage of clinical evaluation. Similarly, we see the new platelet P2Y12 receptor antagonists (prasugrel, ticagrelor, cangrelor, elinogrel), thromboxane receptor antagonists (terutroban) or PAR 1‑type thrombin receptor antagonists (SCH 530348). Some from within this array of drugs, e. g. prasugrel, have now been released for clinical use, while others have just entered the clinical testing stage.

Key words:
antiplatelet agents – P2Y12 receptor antagonists – PAR 1‑type receptor antagonists – TXA2 receptor antagonists – prasugrel – ticagrelor – cangrelor – SCH 530348 – terutroban


Sources

1. ClinicalTrials.gov. [http:/ / clinicaltrials.gov/ ].

2. Van Bockstaele F, Holz JB, Revets H. The development of nanobodies for therapeutic applications. Curr Opin Investig Drugs 2009; 10: 1212– 1224.

3. De Meyer SF, Vanhoorelbeke K, Ulrichts H et al. Development of monoclonal antibodies that inhibit platelet adhesion or aggregation as potential anti‑thrombotic drugs. Cardiovasc Hematol Disord Drug Targets 2006; 6: 191– 207.

4. Gilbert JC, DeFeo- Fraulini T, Hutabarat RM et al. First- in‑human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers. Circulation 2007; 116: 2678– 2686.

5. Mega JL, Close SL, Wiviott SD et al. Cytochrome P- 450 Polymorphisms and Response to Clopidogrel. N Engl J Med 2009; 360: 411– 413.

6. Simon T, Verstuyft C, Mary- Krause M. French Registry of Acute ST‑Elevation and Non- ST‑Elevation Myocardial Infarction (FAST‑MI) Investigators. Genetic Determinants of Response to Clopidogrel and Cardiovascular Events. N Engl J Med 2009; 360: 363– 375.

7. Montalescot G, Wiviott SD, Braunwald E. TRITON- TIMI 38 investigators. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST‑elevation myocardial infarction (TRITON- TIMI 38): double‑blind, randomised controlled trial. Lancet 2009; 373: 723– 731.

8. HOTLINE I, PLATO favours ticagrelor over clopidogrel in ACS. Eur Heart J 2009; 30: 2541.

9. Bhatt DL, Lincoff AM, Gibson CM. CHAMPION PLATFORM Investigators. Intravenous platelet blockade with cangrelor during PCI. N Engl J Med 2009; 361: 2330– 2341.

10. Hildemann SK, Bode C. Improving antiplatelet therapy for atherothrombotic disease: preclinical results with SCH 530348, the first oral thrombin receptor antagonist selective for PAR- 1. Hamostaseologie 2009; 29: 349– 355.

11. Oestreich J. SCH- 530348, a thrombin receptor (PAR- 1) antagonist for the prevention and treatment of atherothrombosis. Curr Opin Investig Drugs 2009; 10: 988– 996.

12. Morrow DA, Scirica BM, Fox KA et al. TRA 2(o) P- TIMI 50 Investigators. Evaluation of a novel antiplatelet agent for secondary prevention in patients with a history of atherosclerotic disease: design and rationale for the Thrombin‑Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic Events (TRA 2 degrees P)- TIMI 50 trial. Am Heart J 2009; 158: 335– 341.e3.

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

14. Anninos H, Andrikopoulos G, Pastromas S et al. Triflusal: an old drug in modern antiplatelet therapy. Review of its action, use, safety and effectiveness. Hellenic J Cardiol 2009; 50: 199– 207.

15. Suh JW, Andrikopoulos G, Pastromas S et al. Comparison of triple antiplatelet therapy including triflusal and conventional dual therapy in patients who underwent drug‑eluting stent implantation. Int Heart J 2009; 50: 701– 709.

16. Chamorro A. TP receptor antagonism: a new concept in atherothrombosis and stroke prevention. Cerebrovasc Dis 2009; 27 (Suppl 3): 20– 27.

17. Kirsten R, Erdeg B, Moxter D et al. Platelet aggregation after naftidrofuryl application in vitro and ex vivo. Int J Clin Pharmacol Ther 1995; 33: 81– 84.

18. Zeymer U, Zahn R. Glycoprotein IIb/ IIIa antagonists: new developments. Hamostaseologie 2009; 29: 334– 337.

19. Hallén J, Atar D, Serebruany V. Effects of FX06 In Vitro on Platelet, Coagulation, and Fibrinolytic Biomarkers in Volunteers and Patients With Documented Coronary Artery Disease. Am J Ther 2009 [Epub ahead of print].

20. Ho PM, Maddox TM, Wang L et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009; 301: 937–944.

21. Stanek EJ, Aubert RE, Flockhart DA et al. A National Study of the Effect of Individual Proton Pump Inhibitors on Cardiovascular Outcomes in Patients Treated with Clopiodogrel Following Coronary Stenting: The Clopidogrel Medco Outcomes Study [http://www.scai. org/pdf/20090506Medcoabstract.pdf] (Abstract).

22. Juurlink DN, Gomes T, Ko DT et al. A populationbased study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ 2009; 180: 713–718.

23. Gupta E, Bansal D, Sotos J et al. Risk of Adverse Clinical Outcomes with Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Percutaneous Coronary Intervention. Dig Dis Sci 2009 [Epub ahead of print].

Labels
Paediatric cardiology Internal medicine Cardiac surgery Cardiology
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#