New antiplatelet drugs: Beyond aspirin and clopidogrel

International Journal of Clinical Practice

Volumn 63, Issue 5, 2009, Pages 776-789

  Siddique, A ^a   Butt, M ^a   Shantsila, E ^a   Lip, G Y H ^a  

^a UNIVERSITY DEPARTMENT OF MEDICINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ABCIXIMAB; ACETYLSALICYLIC ACID; ACETYLSALICYLIC ACID 3 (NITROXYMETHYL)PHENYL ESTER; ALPHA TOCOPHEROL; ANTITHROMBOCYTIC AGENT; ARC 1779; CANGRELOR; CLOPIDOGREL; DIPYRIDAMOLE; E 555; EFIENT; HEPARIN; HIRULOG; NITRATE; PLACEBO; PRASUGREL; SCH 530348; STREPTOKINASE; TERUTROBAN; TICAGRELOR; TICLOPIDINE; UNCLASSIFIED DRUG;

BLEEDING; BONE MARROW TOXICITY; BRONCHOSPASM; CLINICAL PRACTICE; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; CORONARY ARTERY THROMBOSIS; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG WITHDRAWAL; DYSPNEA; FLUID RETENTION; HEART INFARCTION; HUMAN; ISCHEMIC HEART DISEASE; LOADING DRUG DOSE; LOW DRUG DOSE; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIDE EFFECT; SINGLE DRUG DOSE; THROMBOCYTOPENIC PURPURA; THROMBOGENESIS; UNSPECIFIED SIDE EFFECT;

ADENOSINE; ADENOSINE MONOPHOSPHATE; ASPIRIN; CLINICAL TRIALS AS TOPIC; CORONARY ARTERY DISEASE; DRUG DESIGN; HUMANS; IMINES; LACTONES; NAPHTHALENES; PIPERAZINES; PLATELET AGGREGATION INHIBITORS; PROPIONIC ACIDS; PYRIDINES; RECEPTORS, PURINERGIC P2; THIOPHENES; TICLOPIDINE;

EID: 64349107420     PISSN: 13685031     EISSN: 17421241     Source Type: Journal    
DOI: 10.1111/j.1742-1241.2009.02058.x     Document Type: Review

References (90)

1. Gasparyan AY, Watson T, Lip GY. The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol 2008 51 : 1829 43.
2. Matsagas M, Jagroop IA, Geroulakos G, Mikhailidis DP. The effect of a loading dose (300 mg) of clopidogrel on platelet function in patients with peripheral arterial disease. Clin Appl Thromb Hemost 2003 9 : 115 20.
3. 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.
4. Chew DP, Bhatt DL, Sapp S, Topol EJ. Increased mortality with oral platelet glycoprotein IIb-IIIa antagonists: a meta-analysis of phase III multicenter randomized trials. Circulation 2001 103 : 201 6.
5. Steering Committee of the Physicians' Health Study Research Group. Final report on the aspirin component of the ongoing Physicians' Health Study. N Engl J Med 1989 321 : 129 35.
6. Hansson L, Zanchetti A, Carruthers SG et al. Effects of intensive bloodpressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998 351 : 1755 62.
7. The Medical Research Council's General Practice Research Framework. Thrombosis prevention trial: randomised trial of low-intensity oral anticoagulation with warfarin and low-dose aspirin in the primary prevention of ischaemic heart disease in men at increased risk. Lancet 1998 351 : 233 41.
8. Collaborative Group of the Primary Prevention Project. Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Lancet 2001 357 : 89 95.
9. Peto R, Gray R, Collins R et al. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed) 1988 296 : 313 6.
10. Ridker PM, Cook NR, Lee IM et al. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. N Engl J Med 2005 352 : 1293 304.
11. Ogawa H, Nakayama M, Morimoto T et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA 2008 300 : 2134 41.
12. Belch J, MacCuish A, Campbell I et al. The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 2008 337 : a1840.
13. Gent M, Blakely JA, Easton JD et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989 1 : 1215 20.
14. Steinhubl SR, Tan WA, Foody JM, Topol EJ. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of Platelet IIb-IIIa Inhibitor for Stenting. JAMA 1999 281 : 806 10.
15. CAPRIE Steering Committee. A randomised, blinded, trial of Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE). Lancet 1996 348 : 1329 39.
16. Hirsch J, Bhatt DL. Comparative benefits of clopidogrel and aspirin in high-risk patient populations. Arch Intern Med 2004 164 : 2106 10.
17. Mehta SR, Yusuf S, Peters RJ et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001 358 : 527 33.
18. Sabatine MS, Cannon CP, Gibson CM et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005 294 : 1224 32.
19. Chen ZM, Jiang LX, Chen YP et al. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005 366 : 1607 21.
20. Gum PA, Kottke-Marchant K, Welsh PA, White J, Topol EJ. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease. J Am Coll Cardiol 2003 41 : 961 5.
21. Matetzky S, Shenkman B, Guetta V et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation 2004 109 : 3171 5.
22. Eikelboom JW, Hirsh J, Weitz JI, Johnston M, Yi Q, Yusuf S. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002 105 : 1650 5.
23. Weber AA, Zimmermann KC, Meyer-Kirchrath J, Schrör K. Cyclooxygenase-2 in human platelets as a possible factor in aspirin resistance. Lancet 1999 353 : 900.
24. Collet JP, Hulot JS, Pena A et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet 2009 373 : 309 17.
25. Muller I, Seyfarth M, Rudiger S et al. Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 2001 85 : 92 3.
26. De Schryver EL, Algra A, van Gijn J. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. Cochrane Database Syst Rev. 2003 1 : CD001820.
27. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study, 2: Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996 143 : 1 13.
28. Sacco RL, Diener HC, Yusuf S et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008 359 : 1238 51.
29. Brener SJ, Barr LA, Burchenal JE et al. Randomized, placebo-controlled trial of platelet glycoprotein IIb-IIIa blockade with primary angioplasty for acute myocardial infarction. ReoPro and Primary PTCA Organization and Randomized Trial (RAPPORT) Investigators. Circulation 1998 98 : 734 41.
30. Montalescot G, Barragan P, Wittenberg O et al. Abciximab before direct angioplasty and stenting in myocardial infarction regarding acute and long-term follow-up. Platelet glycoprotein IIb-IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001 344 : 1895 903.
31. The EPIC Investigatiors. Use of a monoclonal antibody directed against the platelet glycoprotein IIb-IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994 330 : 956 61.
32. Hostetter JC, Bhatt DL. The expanding role of antiplatelet agents in coronary artery disease. A current review of aspirin, glycoprotein IIb-IIIa inhibitors, and the thienopyridines. Minerva Cardioangiol 2003 51 : 31 46.
33. Moliterno DJ, Yakubov SJ, DiBattiste PM et al. Outcomes at 6 months for the direct comparison of tirofiban and abciximab during percutaneous coronary revascularisation with stent placement: the TARGET follow-up study. Lancet 2002 360 : 355 60.
34. 2+ on GP IIb-IIIa interactions with integrilin: enhanced GP IIb-IIIa binding and inhibition of platelet aggregation by reductions in the concentration of ionized calcium in plasma anticoagulated with citrate. Circulation 1997 96 : 1488 94.
35. Batchelor WB, Tolleson TR, Huang Y et al. Randomized COMparison of platelet inhibition with abciximab, tiRofiban and eptifibatide during percutaneous coronary intervention in acute coronary syndromes: the COMPARE trial. Comparison of Measurements of Platelet aggregation with Aggrastat, Reopro, and Eptifibatide. Circulation 2002 106 : 1470 6.
36. The EPISTENT Investigators. Complementary clinical benefits of coronary-artery stenting and blockade of platelet glycoprotein IIb-IIIa receptors. N Engl J Med 1999 341 : 319 27.
37. The PURSUIT Trial Investigators. Inhibition of platelet glycoprotein IIb-IIIa with eptifibatide in patients with acute coronary syndromes. N Engl J Med 1998 339 : 436 43.
38. The PRISM-PLUS Study Investigators. Inhibition of the platelet glycoprotein IIb-IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. N Engl J Med 1998 338 : 1488 97 [published correction appears in N Engl J Med. 1998; 339: 415].
39. Stone GW, Witzenbichler B, Guagliumi G et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008 358 : 2218 30.
40. Brandt JT, Payne CD, Wiviott SD 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.
41. Wiviott SD, Antman EM, Winters KJ et al. 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 73.
42. 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 47.
43. Storey RF, Husted S, Harrington RA et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 2007 50 : 1852 6.
44. Farid NA, Payne CD, Ernest CS II. et al. Prasugrel, a new thienopyridine antiplatelet drug, weakly inhibits cytochrome P450 2B6 in humans. J Clin Pharmacol 2008 48 : 53 9.
45. Weerakkody GJ, Jakubowski JA, Brandt JT et al. 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 2007 100 : 331 6.
46. Matsushima N, Jakubowski JA, Asai F et al. Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: a multiple-dose study in healthy humans. Platelets 2006 17 : 218 26.
47. Asai F, Jakubowski JA, Naganuma H et al. Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: a single ascending dose study in healthy humans. Platelets 2006 17 : 209 17.
48. Jakubowski JA, Payne CD, Brandt JT et al. The platelet inhibitory effects and pharmacokinetics of prasugrel after administration of loading and maintenance doses in healthy subjects. J Cardiovasc Pharmacol 2006 47 : 377 84.
49. Payne CD, Jakubowski JA, Brandt JT et al. Pharmacokinetics and pharmacodynamics of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 receptor antagonist, in healthy subjects. Eur Heart J 2005 26 : 583 4.
50. Jakubowski JA, Matsushima N, Asai F et al. A multiple dose study of prasugrel (CS-747), a novel thienopyridine P2Y(12) inhibitor, compared with clopidogrel in healthy humans. Br J Clin Pharmacol 2007 63 : 421 30.
51. Weerakkody GJ, Jakubowski JA, Brandt JT, Payne CD, Naganuma H, Winters KJ. A 60 mg loading dose of prasugrel produces a lower rate of poor responders compared to a 300 mg loading dose of clopidogrel. Am J Cardiol 2006 98 (Suppl. TCT (Abstract 509): 200M.
52. Weerakkody GJ, Jakubowski JA, Brandt JT, Payne CD, Naganuma H, Winters KJ. Greater inhibition of platelet aggregation and reduced response variability with prasugrel versus clopidogrel: an integrated analysis. J Cardiovasc Pharmacol Therap 2007 12 : 205 12.
53. Payne CD, Li YG, Small DS et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol 2007 50 : 555 62.
54. Jernberg T, Payne CD, Winters KJ 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 73.
55. Wiviott SD, Trenk D, Frelinger AL 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 2007 116 : 2923 32.
56. NCT00357968: Trial in Subjects Undergoing Cardiac Catheterization with Planned PCI with Stenting (PRINCIPLE). Eli Lilly & Co. Ltd. http://www.clinicaltrials.gov (accessed 12 December 2008).
57. Wallentin L, Varenhorst C, James S et al. Prasugrel achieves greater and faster P2Y12receptor-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 : 21 30.
58. Wiviott SD, Antman EM, Gibson M et al. 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 35.
59. Wiviott SD, Braunwald E, McCabe CH et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007 357 : 2001 15.
60. Daiichi Sankyo. Lilly Announce New Prasugrel Head-to-Head Phase III Study against Clopidogrel. Tokio: Daiichi Sankyo Co. Ltd. Press Release 2007, 4 November.
61. Meadows TA, Bhatt DL. Clinical aspects of platelet inhibitors and thrombus formation. Circ Res 2007 100 : 1261 75.
62. Cannon CP, Husted S, Harrington RA et al. 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 51.
63. A Randomised, Double-Blind, Parallel Group, Phase 3, Efficacy and Safety Study of AZD6140 Compared With Clopidogrel for Prevention of Vascular Events in Patients with Non-ST or ST Elevation Acute Coronary Syndromes (ACS) [PLATO - a Study of PLATelet Inhibition and Patient Outcomes], 2006. http://www. clinicaltrials.gov/ct/show/NCT00391872 (accessed 12 December 2008).
64. Greenbaum AB, Grines CL, Bittl JA 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 : 689.
65. Fugate SE, Cudd LA. Cangrelor for treatment of coronary thrombosis. Ann Pharmacol 2006 40 : 926 30.
66. Jagroop IA, Burnstock G, Mikhailidis DP. Both the ADP receptors P2Y1 and P2Y12, play a role in controlling shape change in human platelets. Platelets 2003 14 : 15 20.
67. Frelinger AL 3rd., Jakubowski JA, Li Y et al. The active metabolite of prasugrel inhibits ADP-stimulated thrombo-inflammatory markers of platelet activation: influence of other blood cells, calcium, and aspirin. Thromb Haemost 2007 98 : 192 200.
68. Wang K, Zhou X, Zhou Z et al. Blockade of the platelet P2Y12 receptor by AR-C69931MX sustains coronary artery recanalization and improves the myocardial tissue perfusion in a canine thrombosis model. Arterioscler Thromb Vasc Biol 2003 23 : 357 62.
69. Storey RF, Oldroyd KG, Wilcox KG. Open multicentre study of the P2T receptor antagonist AR-C69931MX assessing safety, tolerability, and activity in patients with acute coronary syndrome. Thromb Haemost 2001 85 : 401 7.
70. Storey RF, Wilcox RG, Heptinstall S. Comparison of the pharmacodynamic effects of the platelet ADP receptor antagonists clopidogrel and AR-C69931MX in patients with ischaemic heart disease. Platelets 2002 13 : 407 13.
71. A Clinical Trial to Demonstrate the Efficacy of Cangrelor. http://www.clinicaltrials.gov/ct2/show/NCT00305162 (accessed 12 December 2008).
72. Antoniades C, Tousoulis D, Stefanadis C. Nitric oxide-releasing aspirin: will it say NO to atherothrombosis? Intl J Cardiol 2007 118 : 170 2.
73. Fiorucci S, Mencarelli A, Mannucci R et al. NCX-4016, a nitric oxide-releasing aspirin, protects endothelial cells against apoptosis by modulating mitochondrial function. FASEB J 2002 16 : 1645 7.
74. Gresele P, Momi S. Pharmacologic profile and therapeutic potential of NCX 4016, a nitric oxide-releasing aspirin, for cardiovascular disorders. Cardiovasc Drug Rev 2006 24 : 148 68.
75. Napoli C, Aldini G, Wallace JL et al. Efficacy and age-related effects of nitric oxide releasing aspirin on experimental restenosis. Proc Natl Acad Sci USA 2002 99 : 1689 94.
76. Cirino G, Calignabno A, Sannicolo F, Primavera A, Del Soldato P, Wallace JL. NCX-4016. Drugs Future 1997 22 : 1231 3.
77. Gresele P, Migliacci R, Bonizzoni E, Sardina M. Nitroaspirin prevents effort induced endothelial dysfunction in intermittent claudication. Circulation 2004 110 (Suppl. III III 520.
78. Fiorucci S, Santucci L, Gresele P, Faccino RM, Del Soldato P, Morelli A. Gastrointestinal safety of NO-aspirin (NCX-4016) in healthy human volunteers: A proof of concept endoscopic study. Gastroenterology 2003 124 : 600 7.
79. Simonet S, Descombes JJ, Vallex MO, Dubuffet T, Lavielle G, Verbeuren TJ. S 18886, a new thromboxane (TP)-receptor antagonist is the active isomer of S 18204 in all species, except in the guinea-pig. Adv Exp Med Biol 1997 433 : 173 6.
80. 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 8.
81. Worth NF, Berry CL, Thomas AC, Campbell JH. S18886, a selective TP receptor antagonist, inhibits development of atherosclerosis in rabbits. Atherosclerosis 2005 183 : 65 73.
82. Viles-Gonzalez JF, Fuster V, Corti R et al. Atherosclerosis regression and TP receptor inhibition: effect of S18886 on plaque size and composition - a magnetic resonance imaging study. Eur Heart J 2005 26 : 1557 61.
83. Belhassen L, Pelle G, Dubois-Rande JL, Adnot S. Improved endothelial function by the thromboxane A2 receptor antagonist S 18886 in patients with coronary artery disease treated with aspirin. J Am Coll Cardiol 2003 41 : 1198 204.
84. 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. Presented at the 56th Annual Scientific Session of the American College of Cardiology, 24-27 March 2007 New Orleans, LA.
85. Schering-Plough Starts Phase III Vascular Disease Trials of SCH-530348. http://www.iddb3.com (accessed 12 December 2008).
86. A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of SCH 530348 in Subjects Undergoing Non-Emergent Percutaneous Coronary Intervention (TRANSCENDENCE), 2006. http://www. clinicaltrials.gov/ct/show/NCT00132912 (accessed 12 December 2008).
87. Schering-Plough Planning Large-scale Phase III ACS Trials of SCH-530348. http://www.iddb3.com (accessed 12 December 2008).
88. 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 86.
89. Lasser G, Guchhait P, Ellsworth JL et al. C1qTNF-related protein-1 (CTRP-1): a vascular wall protein that inhibits collagen-induced platelet aggregation by blocking VWF binding to collagen. Blood 2006 107 : 423 30.
90. Ogihara Y, Muramatsu S, Kaneda Y, Iijima T, Shibutani T. Pharmacological profile of DZ-697b, a novel anti-platelet agent-selective inhibitor of vWF- and collagen-induced platelet aggregation. Blood 2005 106 : 1875.