Current Problems in Cardiology
Volume 35, Issue 3 , Pages 123-170 , March 2010

Antiplatelet Agents in Acute Coronary Syndromes

References 

  1. Meadows TA, Bhatt DL. Clinical aspects of platelet inhibitors and thrombus formation. Circ Res. 2007;100:1261–1275
  2. Fuster V, Moreno PR, Fayad ZA, et al. Atherothrombosis and high-risk plaque (Part I: evolving concepts). J Am Coll Cardiol. 2005;46:937–954
  3. Virmani R, Burke AP, Farb A, et al. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006;47:C13–C18
  4. Lewis HD, Davis JW, Archibald DG, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina (Results of A Veterans Administration Cooperative study). N Engl J Med. 1983;309:396–403
  5. Cairns JA, Gent M, Singer J, et al. Aspirin, sulfinpyrazone, or both in unstable angina (Results of a Canadian multicenter trial). N Engl J Med. 1985;313:1369–1375
  6. 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
  7. Second International Study of Infarct Survival (ISIS-2) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet. 1988;2:349–360
  8. Baigent C, Collins R, Appleby P, et al. ISIS-2: 10 year survival among patients with suspected acute myocardial infarction in randomised comparison of intravenous streptokinase, oral aspirin, both, or neither (The ISIS-2 (Second International Study of Infarct Survival) Collaborative Group). BMJ. 1998;316:1337–1343
  9. Garcia-Dorado D, Theroux P, Tornos P, et al. Previous aspirin use may attenuate the severity of the manifestation of acute ischemic syndromes. Circulation. 1995;92:1743–1748
  10. Berger JS, Stebbins A, Granger CB, et al. Initial aspirin dose and outcome among ST-elevation myocardial infarction patients treated with fibrinolytic therapy. Circulation. 2008;117:192–199
  11. Smith SC, Blair SN, Criqui MH, et al. Preventing heart attack and death in patients with coronary disease. Circulation. 1995;92:2–4
  12. Gasparyan AY, Watson T, Lip GY. The role of aspirin in cardiovascular prevention: implications of aspirin resistance. J Am Coll Cardiol. 2008;51:1829–1843
  13. Serhan CN, Hong S, Gronert K, et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J Exp Med. 2002;196:1025–1037
  14. Weber AA, Zimmermann KC, Meyer-Kirchrath J, et al. Cyclooxygenase-2 in human platelets as a possible factor in aspirin resistance. Lancet. 1999;353:900
  15. Jefferson BK, Foster JH, McCarthy JJ, et al. Aspirin resistance and a single gene. Am J Cardiol. 2005;95:805–808
  16. Undas A, Brummel K, Musial J, et al. Pl(A2) polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury. Circulation. 2001;104:2666–2672
  17. Tantry US, Bliden KP, Gurbel PA. Overestimation of platelet aspirin resistance detection by thrombelastograph platelet mapping and validation by conventional aggregometry using arachidonic acid stimulation. J Am Coll Cardiol. 2005;46:1705–1709
  18. Ayanian JZ, Guadagnoli E, McNeil BJ, et al. Treatment and outcomes of acute myocardial infarction among patients of cardiologists and generalist physicians. Arch Intern Med. 1997;157:2570–2576
  19. Krumholz HM, Radford MJ, Ellerback EF, et al. Aspirin in the treatment of acute myocardial infarction in elderly Medicare beneficiaries: patterns of use and outcomes. Circulation. 1995;92:2841–2847
  20. Bhatt DL, Steg PG, Ohman EM, et al. International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA. 2006;295:180–189
  21. Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345:1809–1817
  22. Andersohn F, Suissa S, Garbe E. Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction. Circulation. 2006;113:1950–1957
  23. Helin-Salmivaara A, Virtanen A, Vesalainen R, et al. NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J. 2006;27:1657–1663
  24. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. 2007;50:e1–e157
  25. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44:E1–E211
  26. Antman EM, Hand M, Armstrong PW, et al. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008;51:210–247
  27. Bhatt DL, Topol EJ. Scientific and therapeutic advances in antiplatelet therapy. Nat Rev Drug Discov. 2003;2:15–28
  28. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol. 2007;49:1505–1516
  29. Sharis PJ, Cannon CP, Loscalzo J. The antiplatelet effects of ticlopidine and clopidogrel. Ann Intern Med. 1998;129:394–405
  30. Balsano F, Rizzon P, Violi F, et al. Antiplatelet treatment with ticlopidine in unstable angina (A controlled multicenter trial. The Studio della Ticlopidina nell'Angina Instabile Group). Circulation. 1990;82:17–26
  31. Schomig A, Neumann FJ, Kastrati A, et al. A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents. N Engl J Med. 1996;334:1084–1089
  32. Steinhubl SR, Ellis SG, Wolski K, et al. Ticlopidine pretreatment before coronary stenting is associated with sustained decrease in adverse cardiac events: data from the evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) Trial. Circulation. 2001;103:1403–1409
  33. Scrutinio D, Cimminiello C, Marubini E, et al. Ticlopidine versus aspirin after myocardial infarction (STAMI) trial. J Am Coll Cardiol. 2001;37:1259–1265
  34. Bhatt DL, Bertrand ME, Berger PB, et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol. 2002;39:9–14
  35. Steinhubl SR, Tan WA, Foody JM, et al. 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;281:806–810
  36. Bertrand ME, Rupprecht HJ, Urban P, et al. Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation. 2000;102:624–629
  37. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;348:1329–1339
  38. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494–502
  39. 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;358:527–533
  40. Steinhubl SR, Berger PB, Mann JT, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411–2420
  41. 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;366:1607–1621
  42. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005;352:1179–1189
  43. 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;294:1224–1232
  44. Zeymer U, Gitt A, Junger C, et al. Clopidogrel in addition to aspirin reduces in-hospital major cardiac and cerebrovascular events in unselected patients with acute ST segment elevation myocardial. Thromb Haemost. 2008;99:155–160
  45. Jensen LO, Maeng M, Kaltoft A, et al. Stent thrombosis, myocardial infarction, and death after drug-eluting and bare-metal stent coronary interventions. J Am Coll Cardiol. 2007;50:463–470
  46. de la Torre-Hernandez JM, Alfonso F, Hernandez F, et al. Drug-eluting stent thrombosis: results from the multicenter Spanish registry ESTROFA (Estudio ESpanol sobre TROmbosis de stents FArmacoactivos). J Am Coll Cardiol. 2008;51:986–990
  47. Chechi T, Vecchio S, Vittori G, et al. ST-segment elevation myocardial infarction due to early and late stent thrombosis a new group of high-risk patients. J Am Coll Cardiol. 2008;51:2396–2402
  48. Iakovou I, Schmidt T, Bonizzoni E, et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA. 2005;293:2126–2130
  49. Pfisterer MBrunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol. 2006;48:2584–2591
  50. Spertus JA, Kettelkamp R, Vance C, et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation. 2006;113:2803–2809
  51. Ho PM, Peterson ED, Wang L, et al. Incidence of death and acute myocardial infarction associated with stopping clopidogrel after acute coronary syndrome. JAMA. 2008;299:532–539
  52. Eisenstein EL, Anstrom KJ, Kong DF, et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA. 2007;297:159–168
  53. Banerjee S, Varghese C, Samuel J, et al. Comparison of the impact of short (<1 year) and long-term (> or =1 year) clopidogrel use following percutaneous coronary intervention on mortality. Am J Cardiol. 2008;102:1159–1162
  54. Cuisset T, Frere C, Quilici J, et al. Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing coronary stenting. J Am Coll Cardiol. 2006;48:1339–1345
  55. 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;109:3171–3175
  56. Lev EI, Patel RT, Maresh KJ, et al. Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention: the role of dual drug resistance. J Am Coll Cardiol. 2006;47:27–33
  57. De Miguel A, Ibanez B, Badimon JJ. Clinical implications of clopidogrel resistance. Thromb Haemost. 2008;100:196–203
  58. Angiolillo DJ, Bernardo E, Ramirez C, et al. Insulin therapy is associated with platelet dysfunction in patients with type 2 diabetes mellitus on dual oral antiplatelet treatment. J Am Coll Cardiol. 2006;48:298–304
  59. Donahoe SM, Stewart GC, McCabe CH, et al. Diabetes and mortality following acute coronary syndromes. JAMA. 2007;298:765–775
  60. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol. 2008;51:256–260
  61. 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
  62. O'Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet. 2009;374:989–997
  63. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009;360:354–362
  64. Hochholzer W, Trenk D, Bestehorn HP, et al. Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol. 2006;48:1742–1750
  65. Patti G, Colonna G, Pasceri V, et al. Randomized trial of high loading dose of clopidogrel for reduction of periprocedural myocardial infarction in patients undergoing coronary intervention: results from the ARMYDA-2 (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty) study. Circulation. 2005;111:2099–2106
  66. Bonello L, Lemesle G, De Labriolle A, et al. Impact of a 600-mg loading dose of clopidogrel on 30-day outcome in unselected patients undergoing percutaneous coronary intervention. Am J Cardiol. 2008;102:1318–1322
  67. von Beckerath N, Taubert D, Pogatsa-Murray G, et al. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation. 2005;112:2946–2950
  68. Montalescot G, Sideris G, Meuleman C, et al. A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial. J Am Coll Cardiol. 2006;48:931–938
  69. Di Sciascio G. Clopidogrel reloading before percutaneous coronary intervention improves outcome in patients with acute coronary syndromes receiving chronic clopidogrel therapy: results of the ARMYDA-RELOAD (Antiplatelet Therapy for Reduction of Myocardial Damage during Angioplasty-RELOAD) randomized trial. Presented at: SCAI-American College of Cardiology Annual Scientific Session, Chicago, IL, March 2008 http://www.cardiosource.com/clinicaltrials/trial.asp?trialID=1679Accessed May 1, 2009
  70. Di Sciascio G. Antiplatelet therapy for the reduction of myocardial damage during angioplasty-4 (ARMYDA-4). Presented at: Transcatheter Cardiovascular Therapeutics (TCT), Washington DC, October 2007 http://www.cardiosource.com/clinicaltrials/trial.asp?trialID=1610Accessed May 1, 2009
  71. von Beckerath N, Kastrati A, Wieczorek A, et al. A double-blind, randomized study on platelet aggregation in patients treated with a daily dose of 150 or 75 mg of clopidogrel for 30 days. Eur Heart J. 2007;28:1814–1819
  72. Bonello L, Camoin-Jau L, Arques S, et al. Adjusted clopidogrel loading doses according to vasodilator-stimulated phosphoprotein phosphorylation index decrease rate of major adverse cardiovascular events in patients with clopidogrel resistance: a multicenter randomized prospective study. J Am Coll Cardiol. 2008;51:1404–1411
  73. Mehta SR, Bassand JP, Chrolavicius S, et al. Design and rationale of CURRENT-OASIS 7: a randomized, 2 × 2 factorial trial evaluating optimal dosing strategies for clopidogrel and aspirin in patients with ST and non-ST-elevation acute coronary syndromes managed with an early invasive strategy. Am Heart J. 2008;156:1080-8.e1
  74. Fox KA, Mehta SR, Peters R, et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation. 2004;110:1202–1208
  75. Mehta RH, Roe MT, Mulgund J, et al. Acute clopidogrel use and outcomes in patients with non-ST-segment elevation acute coronary syndromes undergoing coronary artery bypass surgery. J Am Coll Cardiol. 2006;48:281–286
  76. Ebrahimi R. Implications of preoperative thienopyridine use prior to coronary bypass graft surgery: a report from the ACUITY trial. Washington, DC: Transcatheter therapeutics (TCT); 2006;
  77. Di Sciascio G. A Prospective, Double-Blind Randomized Trial of Clopidogrel Loading Upstream vs In-lab Administration: antiplatelet therapy for the reduction of myocardial damage during angioplasty-5 (ARMYDA-5). Presented at: Transcatheter Cardiovascular Therapeutics (TCT), Washington DC, October 2007 http://www.tctmd.com/show.aspx?id=54630
  78. Mauri L, Kereiakes D. The Dual Antiplatelet Therapy (DAPT) study. http://www.clinicaltrials.gov/ct2/show/NCT00977938Accessed January 1, 2010
  79. Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006;354:1706–1717
  80. Bhatt DL, Flather MD, Hacke W, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007;49:1982–1988
  81. 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:e9–e16
  82. Angiolillo DJ, Capranzano P. Pharmacology of emerging novel platelet inhibitors. Am Heart J. 2008;156:S10–S15
  83. Farid NA, Smith RL, Gillespie TA, et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos. 2007;35:1096–1104
  84. 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;111:3366–3373
  85. 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;116:2923–2932
  86. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001–2015
  87. Murphy SA, Antman EM, Wiviott SD, et al. Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial. Eur Heart J. 2008;29:2473–2479
  88. Antman EM, Wiviott SD, Murphy SA, et al. Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis. J Am Coll Cardiol. 2008;51:2028–2033
  89. New crossover study shows prasugrel significantly reduced platelet aggregation in patients with acute coronary syndromes compared with clopidogrel at high doses. http://newsroom.lilly.com/ReleaseDetail.cfm?ReleaseID=331820Accessed April 3, 2009
  90. Wiviott SD, Braunwald E, McCabe CH, et al. 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
  91. Wiviott SD, Braunwald E, Angiolillo DJ, et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38. Circulation. 2008;118:1626–1636
  92. A pharmacodynamic comparison of prasugrel versus high dose clopidogrel in subjects with type 2 diabetes mellitus and coronary artery disease. http://clinicaltrials.gov/ct2/show/NCT00642174Accessed May 1, 2009
  93. A comparison of prasugrel and clopidogrel in acute coronary syndrome subjects with unstable angina/non-ST-elevation myocardial infarction who are medically managed. http://www.clinicaltrials.gov/ct2/show/NCT00699998Accessed March 30, 2009
  94. Montalescot G, Wiviott SD, Braunwald E, et al. 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
  95. Husted S, Emanuelsson H, Heptinstall S, et al. 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
  96. 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;50:1844–1851
  97. 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;50:1852–1856
  98. Angiolillo DJ, Guzman LA. Clinical overview of promising nonthienopyridine antiplatelet agents. Am Heart J. 2008;156:S23–S28
  99. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. NEJM. 2009;361:1045–1057
  100. Angiolillo DJ, Bhatt DL, Gurbel PA, et al. Advances in antiplatelet therapy: agents in clinical development. Am J Cardiol. 2009;103:40A–51A
  101. 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.e1–689.e10
  102. Jacobsson F, Swahn E, Wallentin L, et al. Safety profile and tolerability of intravenous AR-C69931MX, a new antiplatelet drug, in unstable angina pectoris and non-Q-wave myocardial infarction. Clin Ther. 2002;24:752–765
  103. Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous platelet blockade with cangrelor during PCI. NEJM. 2009;361:2330–2341
  104. Greenbaum AB, Ohman EM, Gibson CM, et al. Preliminary experience with intravenous P2Y12 platelet receptor inhibition as an adjunct to reduced-dose alteplase during acute myocardial infarction: results of the Safety, Tolerability and Effect on Patency in Acute Myocardial Infarction (STEP-AMI) angiographic trial. Am Heart J. 2007;154:702–709
  105. Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. NEJM. 2009;361:2318–2329
  106. Steinhubl SR, Oh JJ, Oestreich JH, et al. Transitioning patients from cangrelor to clopidogrel: pharmacodynamic evidence of a competitive effect. Thromb Res. 2008;121:527–534
  107. Wallentin L. Maintenance of platelet inhiBition with cangRelor after dIscontinuation of thienopyridines in patients undergoing surGEry (BRIDGE) study. http://www.clinicaltrials.gov/ct2/show/NCT00767507Accessed May 1, 2009
  108. A randomized trial to evaluate the effect of adjunctive antiplatelet therapy with intravenous PTR060128, a selective P2Y12-receptor inhibitor, before primary percutaneous intervention in patients with ST-elevation myocardial infarction (ERASE-MI). http://www.clinicaltrials.gov/ct2/show/NCT00546260Accessed April 4, 2009
  109. A randomized, double-blind, active-controlled trial to evaluate intravenous and oral PRT060128, a selective and reversible PwY12 inhibitor, versus clopidogrel, as a novel antiplatelet therapy in patients undergoing non-urgent PCI (INNOVATE-PCI). http://clinicaltrials.gov/ct2/show/NCT00751231Accessed April 4, 2009
  110. Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med. 1995;332:1553–1559
  111. Bhatt DL, Topol EJ. Current role of platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes. JAMA. 2000;284:1549–1558
  112. Chew DP, Bhatt DL, Sapp S, et al. Increased mortality with oral platelet glycoprotein IIb/IIIa antagonists: a meta-analysis of phase III multicenter randomized trials. Circulation. 2001;103:201–206
  113. Kereiakes DJ, Broderick TM, Roth EM, et al. Time course, magnitude, and consistency of platelet inhibition by abciximab, tirofiban, or eptifibatide in patients with unstable angina pectoris undergoing percutaneous coronary intervention. Am J Cardiol. 1999;84:391–395
  114. Proimos G. Platelet aggregation inhibition with glycoprotein IIb—IIIa inhibitors. J Thromb Thrombolysis. 2001;11:99–110
  115. Simoons ML GUSTO IV-ACS Investigators. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet. 2001;357:1915–1924
  116. The CAPTURE Investigators. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet. 1997;349:1429–1435
  117. Topol EJ, Mark DB, Lincoff AM, et al. Outcomes at 1 year and economic implications of platelet glycoprotein IIb/IIIa blockade in patients undergoing coronary stenting: results from a multicentre randomised trial (EPISTENT Investigators. Evaluation of platelet IIb/IIIa inhibitor for stenting). Lancet. 1999;354:2019–2024
  118. 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;98:734–741
  119. Stone GW, Grines CL, Cox DA, et al. Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med. 2002;346:957–966
  120. Montalescot G, Barragan P, Wittenberg O, et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med. 2001;344:1895–1903
  121. De Luca G, Suryapranata H, Stone GW, et al. Abciximab as adjunctive therapy to reperfusion in acute ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. JAMA. 2005;293:1759–1765
  122. Montalescot G, Antoniucci D, Kastrati A, et al. Abciximab in primary coronary stenting of ST-elevation myocardial infarction: a European meta-analysis on individual patients' data with long-term follow-up. Eur Heart J. 2007;28:443–449
  123. Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet. 2001;358:605–613
  124. Topol EJ. Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet. 2001;357:1905–1914
  125. Kastrati A, Mehilli J, Schlotterbeck K, et al. Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial. JAMA. 2004;291:947–954
  126. Ellis SG, Tendera M, de Belder MA, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med. 2008;358:2205–2217
  127. Phillips DR, Scarborough RM. Clinical pharmacology of eptifibatide. Am J Cardiol. 1997;80:11B–20B
  128. The IMPACT-II Investigators. Randomised placebo-controlled trial of effect of eptifibatide on complications of percutaneous coronary intervention: IMPACT-II. Integrilin to Minimise Platelet Aggregation and Coronary Thrombosis-II. Lancet. 1997;349:1422–1428
  129. O'Shea JC, Buller CE, Cantor WJ, et al. Long-term efficacy of platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention. JAMA. 2002;287:618–621
  130. The ESPRIT Investigators. Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial). Lancet. 2000;356:2037–2044
  131. Giugliano RP, White JA, Bode C, et al. Early versus delayed, provisional eptifibatide in acute coronary syndromes. N Engl J Med. 2009;360:2176–2190
  132. De Luca G, Gibson CM, Bellandi F, et al. Early glycoprotein IIb-IIIa inhibitors in primary angioplasty (EGYPT) cooperation: an individual patient data meta-analysis. Heart. 2008;94:1548–1558
  133. Ohman EM, Kleiman NS, Gacioch G, et al. Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with Integrilin in acute myocardial infarction (Results of a randomized, placebo-controlled, dose-ranging trial. IMPACT-AMI Investigators). Circulation. 1997;95:846–854
  134. Brener SJ, Zeymer U, Adgey AA, et al. Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction: the Integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial. J Am Coll Cardiol. 2002;39:377–386
  135. Giugliano RP, Roe MT, Harrington RA, et al. Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the Integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial. J Am Coll Cardiol. 2003;41:1251–1260
  136. Zeymar U. Eptifibatide Versus Abciximab in Primary PCI for Acute ST Elevation Myocardial Infarction (EVA-AMI). Orlando, FL, American Heart Association, November, 2007. http://www.cardiosource.com/clinicaltrials/trial.asp?trialID=1621
  137. Gibson CM, Kirtane AJ, Murphy SA, et al. Early initiation of eptifibatide in the emergency department before primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: results of the Time to Integrilin Therapy in Acute Myocardial Infarction (TITAN)-TIMI 34 trial. Am Heart J. 2006;152:668–675
  138. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med. 1998;338:1498–1505
  139. Platelet Receptor Inhibition in Ischemic Syndrome management in Patients Limited by Unstable Signs and Symptoms (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;338:1488–1497
  140. Cohen M, Gensini GF, Maritz F, et al. The safety and efficacy of subcutaneous enoxaparin versus intravenous unfractionated heparin and tirofiban versus placebo in the treatment of acute ST-segment elevation myocardial infarction patients ineligible for reperfusion (TETAMI): a randomized trial. J Am Coll Cardiol. 2003;42:1348–1356
  141. Valgimigli M, Campo G, Percoco G, et al. Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial. JAMA. 2008;299:1788–1799
  142. Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet. 2002;359:189–198
  143. Roffi M, Chew DP, Mukherjee D, et al. Platelet glycoprotein IIb/IIIa inhibitors reduce mortality in diabetic patients with non-ST-segment-elevation acute coronary syndromes. Circulation. 2001;104:2767–2771
  144. 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;106:1470–1476
  145. De Luca G, Grazia U, Cassetti E, et al. Benefits from small molecule administration as compared with abciximab among patient with ST-segment elevation myocardial infarction treated with primary angioplasty. J Am Coll Cardiol. 2009;53:1668–1673
  146. Kastrati A, Mehilli J, Neumann FJ, et al. Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA. 2006;295:1531–1538
  147. Sabatine MS, Hamdalla HN, Mehta SR, et al. Efficacy and safety of clopidogrel pretreatment before percutaneous coronary intervention with and without glycoprotein IIb/IIIa inhibitor use. Am Heart J. 2008;155:910–917
  148. Lee SW, Park SW, Kim YH, et al. Comparison of triple versus dual antiplatelet therapy after drug-eluting stent implantation (from the DECLARE-Long trial). Am J Cardiol. 2007;100:1103–1108
  149. Lee SW, Park SW, Kim YH, et al. Drug-eluting stenting followed by cilostazol treatment reduces late restenosis in patients with diabetes mellitus the DECLARE-DIABETES Trial (A Randomized Comparison of Triple Antiplatelet Therapy with Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation in Diabetic Patients). J Am Coll Cardiol. 2008;51:1181–1187
  150. Han Y, Li Y, Wang S, et al. Cilostazol in addition to aspirin and clopidogrel improves long-term outcomes after percutaneous coronary intervention in patients with acute coronary syndromes: a randomized, controlled study. Am Heart J. 2009;157:733–739
  151. Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci. 1996;143:1–13
  152. De Schyrver EL, Algra A, Van Gijn J. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. Cochrane Database Syst Rev. 2004;1:CD001820
  153. Klimt CR, Knatterud GL, Stamler J, et al. Persantine-Aspirin Reinfarction Study (Part II. Secondary coronary prevention with persantine and aspirin). J Am Coll Cardiol. 1986;7:251–269
  154. Becker RC, Moliterno DJ, Jennings LK, et al. 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
  155. A multicenter, randomized, double-blind, placebo-controlled study to evaluated the safety and efficacy of SCH 530348 in addition to standard of care in subjects with acute coronary syndrome: Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA-CER). http://www.clinicaltrials.gov/ct2/show/NCT00527943Accessed April 19, 2009
  156. A double-blind study of E5555 in Japanese patients with acute coronary syndrome. http://www.clinicaltrials.gov/ct2/show/NCT00619164Accessed April 19, 2009
  157. A randomized, double-blind, placebo-controlled study of the safety and tolerability of E5555, and its effects on clinical events and biomarkers in patients with non-ST-segment elevation acute coronary syndrome. http://www.clinicaltrials.gov/ct2/show/NCT00548587Accessed April 19, 2009
  158. Fox KA, Steg PG, Eagle KA, et al. Decline in rates of death and heart failure in acute coronary syndromes, 1999-2006. JAMA. 2007;297:1892–1900
  159. Rogers WJ, Frederick PD, Stoehr E, et al. Trends in presenting characteristics and hospital mortality among patients with ST elevation and non-ST elevation myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006. Am Heart J. 2008;156:1026–1034

PII: S0146-2806(09)00147-9

doi: 10.1016/j.cpcardiol.2009.11.002

Current Problems in Cardiology
Volume 35, Issue 3 , Pages 123-170 , March 2010

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