European Journal of Internal Medicine
Volume 20, Issue 8 , Pages 733-738 , December 2009

New antiplatelet agents: Why they are needed

  • Massimo Franchini

      Affiliations

    • Immunohematology and Transfusion Center, Department of Pathology and Laboratory Medicine, University Hospital of Parma, Italy
  • ,
  • Pier Mannuccio Mannucci

      Affiliations

    • Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milan, Italy
    • Corresponding Author InformationCorresponding author. Via Pace, 9, 20122 Milan, Italy. Tel.: +39 025 5035422; fax: +39 025 0320723.

Received 5 June 2009 ,Revised 28 July 2009 ,Accepted 9 September 2009.

References 

  1. Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, et al. American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics—2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2007;115:e69–e171
  2. Langer HF, Gawaz M. Platelet–vessel wall interactions in atherosclerotic disease. Thromb Haemost. 2008;99:480–486
  3. Angiolillo DJ, Bhatt DL, Gurbel PA, Jennings LK. Advances in antiplatelet therapy: agents in clinical development. Am J Cardiol. 2009;103:40A–51A(suppl)
  4. Xiang Y-Z, Kang LY, Gao XM, Shang HC, Zhang JH, Zhang BL. Strategies for antiplatelet targets and agents. Thromb Res. 2008;123:35–49
  5. Antithrombotic Trialists' Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71–86
  6. ESPRIT Study GroupHalkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006;20(367):1665–1673
  7. Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Méneveau N, Steg PG, et al. 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
  8. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354–362
  9. Rich JD, Wiviott SD. New antiplatelet therapies for acute coronary syndromes. Curr Cardiol Rep. 2007;9:303–311
  10. Chen L, Bracey AW, Radovancevic R, Cooper JR, Collard CD, Vaughn WK, et al. Clopidogrel and bleeding in patients undergoing elective coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2004;128:425–431
  11. Sugidachi A, Asai F, Ogawa T, Inoue T, Koike H. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol. 2000;129:1439–1446
  12. Riley AB, Tafreshi MJ, Haber SL. Prasugrel: a novel antiplatelet agent. Am J Health Syst Pharm. 2008;65:1019–1028
  13. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic and clinical outcome. Circulation. 2009;119:2553–2560
  14. Angiolillo DJ, Guzman LA. Clinical overview of promising nonthienopyridine antiplatelet agents. Am Heart J. 2008;156(Suppl. 2):S23–S28
  15. Serebruany V, Shalito I, Kopyleva O. Prasugrel development — claims and achievements. Thromb Haemost. 2009;101:14–22
  16. Brandt JT, Payne CD, Wiviott SD, Weerakkody G, Farid NA, Small DS, et al. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am Heart J. 2007;153(66):e9–e16
  17. Payne CD, Li YG, Small DS, Ernest CS, Farid NA, Jakubowski JA, et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol. 2007;50:555–562
  18. Jakubowski JA, Matsushima N, Asai F, Naganuma H, Brandt JT, Hirota T, 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;63:421–430
  19. Jernberg T, Payne CD, Winters KJ, Darstein C, Brandt JT, Jakubowski JA, et al. 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. 2006;27:1166–1173
  20. Wiviott SD, Antman EM, Winters KJ, Weerakkody G, Murphy SA, Behounek BD, et al. JUMBO-TIMI 26 Investigators 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;111:3366–3373
  21. Wiviott SD, Trenk D, Frelinger AL, O'Donoghue M, Neumann FJ, Michelson AD, et al. 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;116:2923–2932
  22. Wiviott SD, Antman EM, Gibson CM, Montalescot G, Riesmeyer J, Weerakkody G, et al. TRITON-TIMI 38 Investigators 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. 2006;152:627–635
  23. Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. TRITON-TIMI 38 Investigators Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–2015
  24. Wiviott SD, Braunwald E, McCabe CH, Horvath I, Keltai M, Herrman JP, et al. TRITON-TIMI 38 Investigators 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. 2008;371:1353–1363
  25. Fugate SE, Cudd LA. Cangrelor for treatment of coronary thrombosis. Ann Pharmacol. 2006;40:925–930
  26. Greenbaum AB, Grines CL, Bittl JA, Becker RC, Kereiakes DJ, Gilchrist IC, et al. Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial. Am Heart J. 2006;151:e1–e10
  27. Sabatine MS. Novel antiplatelet strategies in acute coronary syndromes. Clev Clin J Med. 2009;76:S8–S15
  28. Van Giezen JJ, Humphries RG. Preclinical and clinical studies with selective reversible direct P2Y12 antagonists. Semin Thromb Haemost. 2005;31:195–204
  29. Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J. 2006;27:1038–1047
  30. Cannon CP, Husted S, Harrington RA, Scirica BM, Emanuelsson H, Peters G, et al. DISPERSE-2 Investigators 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. 2007;50:1844–1851
  31. Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov. 2003;2:15–28
  32. Becker RC, Moliterno DJ, Jennings LK, Pieper KS, Pei J, Niederman A, et al. TRA-PCI Investigators Safety and tolerability of SCH 530348 in patients undergoing non-urgent percutaneous coronary intervention: a randomised, double-blind, placebo-controlled phase II study. Lancet. 2009;373:919–928
  33. Chamorro A. TP receptor antagonism: a new concept in atherothrombosis and stroke prevention. Cerebrovasc Dis. 2009;27:20–27
  34. Cayatte AJ, Du Y, Oliver-Krasinski J, Lavielle G, Verbeuren TJ, Cohen RA. The thromboxane receptor antagonist S18886 but not aspirin inhibits atherogenesis in apo E-deficient mice: evidence that eicosanoids other than thromboxane contribute to atherosclerosis. Arterioscler Thromb Vasc Biol. 2000;20:1724–1728

PII: S0953-6205(09)00182-4

doi: 10.1016/j.ejim.2009.09.005

European Journal of Internal Medicine
Volume 20, Issue 8 , Pages 733-738 , December 2009