Advances in Antiplatelet Therapy: Agents in Clinical Development

American Journal of Cardiology

Volumn 103, Issue 3 SUPPL., 2009, Pages 40A-51A

  Angiolillo, Dominick J ^a   Bhatt, Deepak L ^b   Gurbel, Paul A ^c   Jennings, Lisa K ^d  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c SINAI CENTER FOR THROMBOSIS RESEARCH   (United States)

^d UNIVERSITY OF MEMPHIS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ANTITHROMBOCYTIC AGENT; CANGRELOR; CLOPIDOGREL; DRUG METABOLITE; PLACEBO; PRASUGREL; R 138727; R 95913; SCH 530348; THIOLACTONE; TICAGRELOR; TICLOPIDINE; UNCLASSIFIED DRUG;

ACUTE CORONARY SYNDROME; ARTICLE; BLEEDING; CLINICAL TRIAL; CORONARY ARTERY DISEASE; DRUG ABSORPTION; DRUG ACTIVITY; DRUG BINDING; DRUG HALF LIFE; DRUG INHIBITION; DRUG MECHANISM; DRUG METABOLISM; DRUG STRUCTURE; DRUG TREATMENT FAILURE; DYSPNEA; HEART INFARCTION; HUMAN; ISCHEMIA; LOADING DRUG DOSE; NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; PRIORITY JOURNAL; REVASCULARIZATION; SIDE EFFECT; THROMBOCYTE AGGREGATION;

EID: 58249143713     PISSN: 00029149     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.amjcard.2008.11.023     Document Type: Article

References (38)

1. Savi P., Pereillo J.M., Uzabiaga M.F., Combalbert J., Picard C., Maffrand J.P., Pascal M., and Herbert J.M. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 84 (2000) 891-896
2. Yusuf S., Zhao F., Mehta S.R., Chrolavicius S., Tognoni G., and Fox K.K. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345 (2001) 494-502
3. Angiolillo D.J., Fernandez-Ortiz A., Bernardo E., Ramirez C., Barrera-Ramirez C., Sabate M., Hernandez R., Moreno R., Escaned J., Alfonso F., et al. Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting. Thromb Res 115 (2005) 101-108
4. Angiolillo D.J., Fernandez-Ortiz A., Bernardo E., Alfonso F., Macaya C., Bass T.A., and Costa M.A. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 49 (2007) 1505-1516
5. Gurbel P.A., Bliden K.P., Hiatt B.L., and O'Connor C.M. Clopidogrel for coronary stenting: response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 107 (2003) 2908-2913
6. Gurbel P.A., and Bliden K.P. Durability of platelet inhibition by clopidogrel. Am J Cardiol 91 (2003) 1123-1125
7. Müller I., Besta F., Schulz C., Massberg S., Schönig A., and Gawaz M. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 89 (2003) 783-787
8. Sugidachi A., Asai F., Ogawa T., Inoue T., and Koike H. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol 129 (2000) 1439-1446
9. 12 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 29 (2008) 21-30
10. Weerakkody G.J., Jakubowski J.A., Brandt J.T., Farid N.A., Payne C.D., Zhu J., Warner M.R., Naganuma H., and Winters K.J. Comparison of speed of onset of platelet inhibition after loading doses of clopidogrel versus prasugrel in healthy volunteers and correlation with responder status. Am J Cardiol 100 (2007) 331-336
11. Rehmel J.L., Eckstein J.A., Farid N.A., Heim J.B., Kasper S.C., Kurihara A., Wrighton S.A., and Ring B.J. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab Dispos 34 (2006) 600-607
12. Farid N.A., Smith R.L., Gillespie T.A., Rash T.J., Blair P.E., Kurihara A., and Goldberg M.J. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos 35 (2007) 1096-1104
13. Niitsu Y., Jakubowski J.A., Sugidachi A., and Asai F. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost 31 (2005) 184-194
14. Brandt J.T., Payne C.D., Wiviott S.D., Weerakkody G., Farid N.A., Small D.S., Jakubowski J.A., Nakanuma H., and Winters K.J. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am Heart J 153 (2007) e9-e16
15. Sugidachi A., Ogawa T., Kurihara A., Hagihara K., Jakubowski J.A., Hashimoto M., Niitsu Y., and Asai F. The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel's active metabolite. J Thromb Haemost 5 (2007) 1545-1551
16. Jernberg T., Payne C.D., Winters K.J., Darstein C., Brandt J.T., Jakubowski J.A., Naganuma H., Siegbahn A., and Wallentin L. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur Heart J 27 (2006) 1166-1173
17. Wiviott S.D., Trenk D., Frelinger A.L., O'Donoghue M., Neumann F.J., Michelson A.D., Angiolillo D.J., Hod H., Montalescot G., Miller D.L., et al. 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 116 (2007) 2923-2932
18. 12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation 111 (2005) 3366-3373
19. Wiviott S.D., Antman E.M., Gibson C.M., Montalescot G., Riesmeyer J., Weerakkody G., Winters K.L., Warmke J.W., McCabe C.H., and Braunwald E. Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet Inhibition with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). Am Heart J 152 (2006) 627-635
20. Wiviott S.D., Braunwald E., McCabe C.H., Montalescot G., Ruzyllo W., Gottlieb S., Neumann F.J., Ardissino D., De Servi S., Murphy S.A., et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 357 (2007) 2001-2015
21. Wiviott S.D., Braunwald E., McCabe C.H., Horvath I., Keltai M., Herrman J.P., van de Werf F., Downey W.E., Scirica B.M., Murphy S.A., and Antman E.M. Intensive oral antiplatelet therapy for reduction of ischaemic events including stent thrombosis in patients with acute coronary syndromes treated with percutaneous coronary intervention and stenting in the TRITON-TIMI 38 trial: a subanalysis of a randomised trial. Lancet 371 (2008) 1353-1363
22. Ingall A.H., Dixon J., Bailey A., Coombs M.E., Cox D., McInally J.I., Hunt S.F., Kindon N.D., Teobald B.J., Willis P.A., et al. Antagonists of the platelet P2T receptor: a novel approach to antithrombotic therapy. J Med Chem 42 (1999) 213-220
23. 12 receptor by AR-C69931MX sustains coronary artery recanalization and improves the myocardial tissue perfusion in a canine thrombosis model. Arterioscler Thromb Vasc Biol 23 (2003) 357-362
24. Storey R.F., Judge H.M., Wilcox R.G., and Heptinstall S. Inhibition of ADP-induced P-selectin expression and platelet-leukocyte conjugate formation by clopidogrel and the P2Y12 receptor antagonist AR-C69931MX but not aspirin. Thromb Haemost 88 (2002) 488-494
25. Storey R.F., Sanderson H.M., White A.E., May J.A., Cameron K.E., and Heptinstall S. The central role of the P(2T) receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity. Br J Haematol 110 (2000) 925-934
26. Storey R.F., Wilcox R.G., and Heptinstall S. Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease. Platelets 13 (2002) 407-413
27. Meadows T.A., and Bhatt D.L. Clinical aspects of platelet inhibitors and thrombus formation. Circ Res 100 (2007) 1261-1275
28. Steinhubl S.R., Oh J.J., Oestreich J.H., Ferraris S., Nessel C.C., Schwabe K.D., Charnigo R., and Akers W.S. Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect. Thromb Res 121 (2007) 527-534
29. van Giezen J.J., and Humphries R.G. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Hemost 31 (2005) 195-204
30. 12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J 27 (2006) 1038-1047
31. Cannon C.P., Husted S., Harrington R.A., Scirica B.M., Emanuelsson H., Peters G., and Storey R.F. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. J Am Coll Cardiol 50 (2007) 1844-1851
32. Kahn M.L., Nakanishi-Matsui M., Shapiro M.J., Ishihara H., and Coughlin S.R. Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin. J Clin Invest 103 (1999) 879-887
33. Holinstat M., Voss B., Bilodeau M.L., and Hamm H.E. Protease-activated receptors differentially regulate human platelet activation through a phosphatidic acid-dependent pathway. Mol Pharmacol 71 (2007) 686-694
34. Wu C.C., and Teng C.M. Comparison of the effects of PAR1 antagonists, PAR4 antagonists, and their combinations on thrombin-induced human platelet activation. Eur J Pharmacol 546 (2006) 142-147
35. Keuren J.F., Wielders S.J., Ulrichts H., Hackeng T., Heemskerk J.W., Deckmyn H., and Bevers E.M. Synergistic effect of thrombin on collagen-induced platelet procoagulant activity is mediated through protease-activated receptor-1. Arterioscler Thromb Vasc Biol 25 (2005) 1499-1505
36. Colognato R., Slupsky J.R., Jendrach M., Burysek L., Syrovets T., and Simmet T. Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cells. Blood 102 (2003) 2645-2652
37. Moliterno D.J., Becker R.C., Jennings L.K., Berman G., Yang B., Strony J., Veltry E., Harrington R.A., and TRA-PCI Study Investigators. Results of a multinational randomized, double-blind, placebo-controlled study of a novel thrombin receptor antagonist (SCH 530348) in percutaneous coronary intervention. [Abstract]. Last update: 2007. http://www.spectrumscience.com/assets/files/acc07/i2%20LBCT%20Sat%2012%2 0pm/Moliterno%20Abstract.pdf Accessed June 27, 2007.
38. Jennings L.K., Earhart A., and Becker R.C. Thrombin receptor antagonist (TRA; SCH530348) is a selective, potent inhibitor of PAR1 activity with predictable pharmacokinetics. [abstract]. Circulation 116 (2007) 674