Download PDF
Thromb Haemost 2008; 100(02): 184-195
DOI: 10.1160/TH08-03-0174
Review Article
Schattauer GmbH

Advances in antithrombotic therapy as adjunct to reperfusion therapies for ST-segment elevation myocardial infarction

Giuseppe De Luca
1   Division of Cardiology, “Maggiore della Carità” Hospital, Eastern Piedmont University “A. Avogadro”, Novara, Italy
,
Paolo Marino
1   Division of Cardiology, “Maggiore della Carità” Hospital, Eastern Piedmont University “A. Avogadro”, Novara, Italy
› Author Affiliations
Further Information

Publication History

Received 18 March 2008

Accepted after major revision: 29 May 2008

Publication Date:
22 November 2017 (online)

    Permissions and Reprints

Summary

The treatment of ST-segment elevation myocardial infarction (STEMI) has improved over the past decades, mainly due to reperfusion therapies. The aim of this article is to provide an updated review of adjunctive antithrombotic therapy to reperfusion strategies for STEMI. As compared to unfractionated heparin (UFH), among patients treated with thrombolysis, low-molecular- weight heparins (LMWHs),mainly enoxaparin, fonda-parinux and clopidogrel have been shown to improve outcome in terms of death and reinfarction, whereas GP IIb-IIIa inhibitors, mainly abciximab, and direct thrombin inhibitors have reduced reinfarction, but not mortality. Among patients undergoing primary angioplasty, early UFH should still be regarded as the gold standard in anticoagulation therapy. In addition to ASA, early GP IIb-IIIa inhibitors, especially abciximab, should be considered since it has been shown to provide further benefits in terms of preprocedural recanalization. Despite the positive results observed in the HORIZONS trial, additional studies are needed to investigate the role of bivalirudin as compared to abciximab administration. In our opinion, bivalirudin may be considered instead of GP IIb-IIIa inhibitors among STEMI patients at high risk for bleeding complications. Due to the very low mortality currently achieved by primary angioplasty, a further reduction in short- or medium-term mortality would be quite improbable to be observed. Thus, additional endpoints, such as infarct size and myocardial perfusion, may be considered in future randomized trials among patients undergoing mechanical revascularization for STEMI.

Keywords

Acute myocardial infarction - direct antithrombin agents - atherothrombosis - antiplatelet drugs - heparins / LMWH
 

  • References

  • 1 Keeley EC, Boura JA, Grines CL. Primary angio-plasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13-20.
    CrossrefPubMedGoogle Scholar
  • 2 Zhu MM, Feit A, Chadow H. et al. Primary stent implantation compared with primary balloon angioplasty for acute myocardial infarction: a meta-analysis of randomized clinical trials. Am J Cardiol 2001; 88: 297-301.
    CrossrefPubMedGoogle Scholar
  • 3 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. J Am Med Assoc 2005; 293: 1759-1765.
    CrossrefPubMedGoogle Scholar
  • 4 Antman EM, Anbe DT, Armstrong PW. et al. American College of Cardiology; American Heart Association Task Force on Practice Guidelines; Canadian Cardiovascular Society 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). Circulation 2004; 110: e82-292.
    PubMedGoogle Scholar
  • 5 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: developed in collaboration With the Canadian Cardiovascular Society endorsed by the American Academy of Family Physicians: 2007 Writing Group to Review New Evidence and Update the ACC/AHA 2004 Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction, Writing on Behalf of the 2004 Writing Committee. Circulation 2008; 117: 296-329.
    CrossrefPubMedGoogle Scholar
  • 6 van 't Hof AW, Liem A, Suryapranata H. et al. on the behalf of the Zwolle Myocardial Infarction Study Group Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction. Myocardial Blush Grade. Circulation 1998; 97: 2302-2306.
    CrossrefPubMedGoogle Scholar
  • 7 Stone GW, Peterson MA, Lansky AJ. et al. Impact of normalized myocardial perfusion after successful angioplasty in acute myocardial infarction. J Am Coll Cardiol 2002; 39: 591-597.
    CrossrefPubMedGoogle Scholar
  • 8 De Luca G, van't Hof AW, Ottervanger JP. et al. Unsuccessful reperfusion in patients with ST - segment elevation myocardial infarction treated by primary angioplasty. Am Heart J 2005; 150: 557-562.
    CrossrefPubMedGoogle Scholar
  • 9 De Luca G, Ernst N, van't Hof AW. et al. Predictors and clinical implications of early reinfarction after primary angioplasty for ST - segment elevation myocardial infarction. Am Heart J 2006; 151: 1256-1259.
    CrossrefPubMedGoogle Scholar
  • 10 Gibson CM, Karha J, Murphy SA. et al. TIMI Study Group Early and long-term clinical outcomes associated with reinfarction following fibrinolytic administration in the Thrombolysis in Myocardial Infarction trials. J Am Coll Cardiol 2003; 42: 7-16.
    CrossrefPubMedGoogle Scholar
  • 11 Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 2001; 104: 365-372.
    CrossrefPubMedGoogle Scholar
  • 12 Weitz JI, Hudoba M, Massel D. et al. Clot-bound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin III-independent inhibitors. J Clin Invest 1990; 86: 385-391.
    CrossrefPubMedGoogle Scholar
  • 13 Weitz JI. Biological rationale for the therapeutic role of specific antithrombins. Coron Artery Dis 1996; 07: 409-419.
    CrossrefPubMedGoogle Scholar
  • 14 Warkentin TE, Greinacher A, Koster A. Bivalirudin. Thromb Haemost 2008; 99: 830-839.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Nowak G, Schrör K. Hirudin--the long and stony way from an anticoagulant peptide in the saliva of medicinal leech to a recombinant drug and beyond. A historical piece. Thromb Haemost 2007; 98: 116-119.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 16 Cannon CP, McCabe CH, Henry TD. et al. A pilot trial of recombinant desulfatohirudin compared with heparin in conjunction with tissue-type plasminogen activator and aspirin for acute myocardial infarction: results of the Thrombolysis In Myocardial Infarction (TIMI) 5 trial. J Am Coll Cardiol 1994; 23: 993-1003.
    CrossrefPubMedGoogle Scholar
  • 17 Neuhaus KL, Molhoek GP, Zeymer U. et al. Recombinant hirudin (Lepirudin) for the improvement of thrombolysis with streptokinase in patients with acute myocardial infarction: results of the HIT - 4 trial. J Am Coll Cardiol 1999; 34: 966-973.
    CrossrefPubMedGoogle Scholar
  • 18 Jang IK, Brown DF, Giugliano RP. et al. A multi-centre, randomized study of argatroban versus heparin as adjunct to tissue plasminogen activator (TPA) in acute myocardial infarction: myocardial infarction with novastan and TPA (MINT) study. J Am Coll Cardiol 1999; 33: 1879-1885.
    CrossrefPubMedGoogle Scholar
  • 19 Theroux P, Perez-Villa F, Waters D. et al. Randomized double-blind comparison of two doses of hirulog with heparin as adjunctive therapy to streptokinase to promote early patency of the infarct-related artery in acute myocardial infarction. Circulation 1995; 91: 2132-2139.
    CrossrefPubMedGoogle Scholar
  • 20 White HD, Aylward PE, Frey MJ. et al. Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Circulation 1997; 96: 2155-2161.
    CrossrefPubMedGoogle Scholar
  • 21 Lee L V. Initial experience with hirudin and streptokinase in acute myocardial infarction: results of the Thrombolysis In Myocardial Infarction (TIMI) 6 trial. Am J Cardiol 1995; 75: 7-13.
    CrossrefPubMedGoogle Scholar
  • 22 The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIa Investigators, Randomized trial of intravenous heparin versus recombinant hirudin for acute coronary syndromes. Circulation. 1994 90. 1631-1637.
    PubMedGoogle Scholar
  • 23 Antman EM. Hirudin in acute myocardial infarction: safety report from the Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9A trial. Circulation 1994; 90: 1624-1630.
    CrossrefPubMedGoogle Scholar
  • 24 Neuhaus KL, von Essen R, Tebbe U. et al. Safety observations from the pilot phase of the randomized r-Hirudin for Improvement of Thrombolysis (HIT-III) study: a study of the Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausarzte. Circulation 1994; 90: 1638-1642.
    CrossrefPubMedGoogle Scholar
  • 25 The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb Investigators, A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. N Engl J Med 1996; 335: 775-782.
    CrossrefPubMedGoogle Scholar
  • 26 Antman EM. Hirudin in acute myocardial infarction: Thrombolysis and Thrombin Inhibition in Myocardial Infarction (TIMI) 9B trial. Circulation 1996; 94: 911-921.
    CrossrefPubMedGoogle Scholar
  • 27 White HD. Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrino-lytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Hirulog and Early Reperfusion or Occlusion (HERO) Study Group. Lancet 2001; 358: 1855-1863.
    CrossrefPubMedGoogle Scholar
  • 28 Behar S, Hod H, Kaplinsky E. et al. Argatroban versus heparin as adjuvant therapy for thrombolysis for acute myocardial infarction: safety consideration AR-GAMI-2 study. Circulation 1998; 98 (Suppl. 01) 453-454 [Abstract].
    PubMedGoogle Scholar
  • 29 Stone GW. HORIZONS AMI: A Prospective, Randomized Comparison of Bivalirudin vs. Heparin Plus Glycoprotein IIb/IIIa Inhibitors During Primary Angioplasty in Acute Myocardial Infarction - 30 Day Results http://www.tctmd.com/csportal/appmanager/tctmd/tct2007?_nfpb= true&_pageLabel=TCT2007Content&hdCon=1518296
    PubMedGoogle Scholar
  • 30 Lincoff AM, Bittl JA, Harrington RA. et al. REPLACE-2 Investigators. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. J Am Med Assoc 2003; 289: 853-863.
    CrossrefPubMedGoogle Scholar
  • 31 Stone GW, McLaurin BT, Cox DA. et al. ACUITY Investigators Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006; 355: 2203-2216.
    CrossrefPubMedGoogle Scholar
  • 32 Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight heparin. Thromb Haemost 2008; 99: 807-818.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 33 Ross AM, Molhoek P, Lundergan C. et al. HART II Investigators Randomized comparison of enoxaparin, a low-molecular-weight heparin, with unfractionated heparin adjunctive to recombinant tissue plasminogen activator thrombolysis and aspirin: second trial of Heparin andAspirin ReperfusionTherapy (HART II). Circulation 2001; 104: 648-652.
    CrossrefPubMedGoogle Scholar
  • 34 Antman EM, Louwerenburg HW, Baars HF. et al. Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial. Circulation 2002; 105: 1642-1649.
    CrossrefPubMedGoogle Scholar
  • 35 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.
    CrossrefPubMedGoogle Scholar
  • 36 Wallentin L, Goldstein P, Armstrong PW. et al. Efficacy and safety of tenecteplase in combination with the low-molecular-weight heparin enoxaparin or unfractionated heparin in the prehospital setting: the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 PLUS randomized trial in acute myocardial infarction. Circulation 2003; 108: 135-142.
    CrossrefPubMedGoogle Scholar
  • 37 Wallentin L, Bergstrand L, Dellborg M. et al. Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction-the ASSENT Plus study. Eur Heart J 2003; 24: 897-908.
    CrossrefPubMedGoogle Scholar
  • 38 Baird SH, Menown IB, Mcbride SJ. et al. Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. Eur Heart J 2002; 23: 627-632.
    CrossrefPubMedGoogle Scholar
  • 39 Antman EM, Morrow DA, McCabe CH. et al. ExTRACT-TIMI 25 Investigators Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med 2006; 354: 1477-1488.
    CrossrefPubMedGoogle Scholar
  • 40 Wang XK, ZhangY Ya, ng CM. et al. Use of unfractionated heparin and a low-molecular-weight heparin following thrombolytic therapy for acute ST - segment elevation myocardial infarction. Clin Drug Investig 2006; 26: 341-9.
    CrossrefPubMedGoogle Scholar
  • 41 De Luca G, Marino P. Adjunctive benefits from low-molecular-weight heparins as compared to unfractionated heparin among patients with ST-segment elevation myocardial infarction treated with thrombolysis. A meta-analysis of the randomized trials. Am Heart J 2007; 154: 1085e1-6.
    PubMedGoogle Scholar
  • 42 Bijsterveld NR, Peters RJ, Murphy SA. et al. Recurrent cardiac ischemic events early after discontinuation of short-term heparin treatment in acute coronary syndromes: results from the Thrombolysis in Myocardial Infarction (TIMI) 11B and Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) studies. J Am Coll Cardiol 2003; 42: 2083-2089.
    CrossrefPubMedGoogle Scholar
  • 43 Manoukian SV, Feit F, Mehran R. et al. Impact of major bleeding on 30-day mortality and clinical outcomes in patients with acute coronary syndromes: an analysis from the ACUITY Trial. J Am Coll Cardiol 2007; 49: 1362-1368.
    CrossrefPubMedGoogle Scholar
  • 44 Sinnaeve PR, Huang Y, Bogaerts K. et al. ASSENT- 3 andASSENT- 3 PLUS investigators. Age, outcomes, and treatment effects of fibrinolytic and anti-thrombotic combinations: findings from Assessment of the Safety and Efficacy of a New Thrombolytic (AS-SENT)-3 andASSENT- 3 PLUS. Am Heart J 2006; 152: 684 e1-9..
    PubMedGoogle Scholar
  • 45 White HD, Braunwald E, Murphy SA. et al. Enoxaparin vs. unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction in elderly and younger patients:results from ExTRACT-TIMI 25. Eur Heart J 2007; 28: 1066-1071.
    CrossrefPubMedGoogle Scholar
  • 46 Montalescot G, White HD, Gallo R. et al. STEEPLE Investigators Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med 2006; 355: 1006-1017.
    CrossrefPubMedGoogle Scholar
  • 47 Petitou M, Duchaussoy P, Herbert JM. et al. The synthetic pentasaccharide fondaparinux: first in the class of antithrombotic agents that selectively inhibit coagulation factor Xa. Semin Thromb Hemost 2002; 28: 393-402.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Yusuf S, Mehta SR, Chrolavicius S. et al. OASIS-6 Trial Group Effects of fondaparinux on mortality and reinfarction in patients with acute ST - segment elevation myocardial infarction: the OASIS-6 randomized trial. J Am Med Assoc 2006; 295: 1519-1530.
    CrossrefPubMedGoogle Scholar
  • 49 Ashida SI, Abiko Y. Inhibition of platelet aggregation by a new agent, Ticlopidine. Thromb Haemost 1979; 40: 542-550.
    PubMedGoogle Scholar
  • 50 Bernat A, Mares AM, Defreyn G. et al. Effect of various antiplatelet agents on acute arterial thrombosis in the rat. Thromb Haemost 1993; 70: 812-816.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Gachet C. ADP receptors of platelets and their inhibition. Thromb Haemost 2001; 86: 222-232.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 52 Evangelista V, Manarini S, Dell'Elba G. et al. Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost 2005; 94: 568-577.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 53 Bierbach B, Horstick G, Berg O. et al. Potent low dose platelet inhibitory effects of clopidogrel and aspirin on coronary thrombus formation in an animal model of acute unstable angina. Thromb Haemost 2006; 95: 354-361.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Sabatine MS, Cannon CP, Gibson CM. et al. CLARITY-TIMI 28 Investigators. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005; 352: 1179-1189.
    CrossrefPubMedGoogle Scholar
  • 55 Chen ZM, Jiang LX, Chen YP. et al. COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 2005; 366: 1607-1621.
    CrossrefPubMedGoogle Scholar
  • 56 Mason PJ, Jacobs AK, Freedman JE. Aspirin resistance and atherothrombotic disease. J Am Coll Cardiol 2005; 46: 986-993.
    CrossrefPubMedGoogle Scholar
  • 57 Marcucci R, Paniccia R, Antonucci E. et al. Usefulness of Aspirin Resistance After Percutaneous Coronary Intervention for Acute Myocardial Infarction in Predicting One-Year Major Adverse Coronary Events. Am J Cardiol 2006; 98: 1156-1159.
    CrossrefPubMedGoogle Scholar
  • 58 Wang TH, Bhatt DL, Topol EJ. Aspirin and clopido-grel resistance: an emerging clinical entity. Eur Heart J 2006; 27: 647-654.
    CrossrefPubMedGoogle Scholar
  • 59 Wong S, Morel-Kopp MC, Chen Q. et al. Overcoming aspirin resistance: increased platelet inhibition with combination aspirin and clopidogrel and high dose aspirin therapy in aspirin resistant patients with peripheral vascular disease. Thromb Haemost 2006; 95: 1042-1043.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 60 Wang YX, Vincelette J, da Cunha V. et al. A novel P2Y(12) adenosine diphosphate receptor antagonist that inhibits platelet aggregation and thrombus formation in rat and dog models. Thromb Haemost 2007; 97: 847-855.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 61 Frelinger 3rd AL, 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.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 62 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: 1166-1173.
    CrossrefPubMedGoogle Scholar
  • 63 Wiviott SD, Antman EM, Winters KJ. et al. JUMBO-TIMI 26 Investigators Randomized comparison of prasugrel (CS-747, L Y 640315), a novel thieno-pyridine 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.
    CrossrefPubMedGoogle Scholar
  • 64 Hasegawa M, Sugidachi A, Ogawa T. et al. Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (prasugrel, LY640315), a novel P2Y12 receptor inhibitor. Thromb Haemost 2005; 94: 593-598.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 65 Vilahur G, Casaní L, Badimon L. A thromboxane A2/prostaglandin H2 receptor antagonist (S18886) shows high antithrombotic efficacy in an experimental model of stent-induced thrombosis. Thromb Haemost 2007; 98: 662-669.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 66 Cannon CP, Husted S, Harrington RA. et al. DIS-PERSE-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 DIS-PERSE-2 trial. jJ Am Coll Cardiol. 2007; 50: 1844-1851.
    PubMedGoogle Scholar
  • 67 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.
    CrossrefPubMedGoogle Scholar
  • 68 Wiviott SD, Braunwald E, McCabe CH. et al. TRI-TON-TIMI 38 Investigators Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
    CrossrefPubMedGoogle Scholar
  • 69 Harrington R. 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 PLATe let Inhibition and Patient Outcomes]. http://clinicaltrials.gov/ct2/show/NCT00391872
    PubMedGoogle Scholar
  • 70 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.
    CrossrefPubMedGoogle Scholar
  • 71 Crescente M, Di Castelnuovo A, Iacoviello L. et al. Response variability to aspirin as assessed by the platelet function analyzer (PFA)-100. A systematic review. Thromb Haemost 2008; 99: 14-26.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 72 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.
    CrossrefPubMedGoogle Scholar
  • 73 Morel O, Faure A, Ohlmann P. et al. Impaired platelet responsiveness to clopidogrel identified by flow cytometric vasodilator-stimulated phosphoprotein (VASP) phosphorylation in patients with subacute stent thrombosis. Thromb Haemost 2007; 98: 896-899.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 74 Siller-Matula J, Schrör K, Wojta J. et al. Thienopyridines in cardiovascular disease: focus on clopidogrel resistance. Thromb Haemost 2007; 97: 385-393.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 75 Buonamici P, Marcucci R, Migliorini A. et al. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol 2007; 49: 2312-2317.
    CrossrefPubMedGoogle Scholar
  • 76 von Beckerath N, Pogatsa-Murray G, Wieczorek A. et al. Correlation of a new point-of-care test with conventional optical aggregometry for the assessment of clopidogrel responsiveness. Thromb Haemost 2006; 95: 910-911.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 77 Lordkipanidzé M, Pharand C, Schampaert E. et al. A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J 2007; 28: 1702-1708.
    CrossrefPubMedGoogle Scholar
  • 78 Gurbel PA, Becker RC, Mann KG. et al. Platelet function monitoring in patients with coronary artery disease. J Am Coll Cardiol 2007; 50: 1822-1834.
    CrossrefPubMedGoogle Scholar
  • 79 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; 15: 1814-1819.
    PubMedGoogle Scholar
  • 80 Campo G, Valgimigli M, Gemmati D. et al. Poor responsiveness to clopidogrel: drug-specific or class-effect mechanism? Evidence from a clopidogrel-to-ti-clopidine crossover study. J Am Coll Cardiol 2007; 50: 1132-1137.
    CrossrefPubMedGoogle Scholar
  • 81 Mehta S. CURRENT/OASIS 7: Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS. http://clinicaltrials.gov/ct2/show/NCT00335452
    PubMedGoogle Scholar
  • 82 Neumann FJ, Blasini R, Schmitt C. et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myo-cardial infarction. Circulation 1998; 98: 2695-2701.
    CrossrefPubMedGoogle Scholar
  • 83 Petronio AS, Rovai D, Musumeci G. et al. Effects of abciximab on microvascular integrity and left ventricular functional recovery in patients with acute infarction treated by primary coronary angioplasty. Eur Heart J 2003; 24: 67-76.
    PubMedGoogle Scholar
  • 84 Coller BS. Potential non-glycoprotein IIb/IIIa effects of abciximab. Am Heart J 1999; 138: S1-5.
    CrossrefPubMedGoogle Scholar
  • 85 Schwarz M, Nordt T, Bode C. et al. The GP IIb/IIIa inhibitor abciximab (c7E3) inhibits the binding of various ligands to the leukocyte integrin Mac-1 (CD11b/CD18, alphaMbeta2). Thromb Res 2002; 107: 121-128.
    CrossrefPubMedGoogle Scholar
  • 86 Eisenberg PR, Sobel BE, Jaffe AS. Activation of prothrombin accompanying thrombolysis with recom-binant tissue-type plasminogen activator. J Am Coll Cardiol 1992; 19: 1065.
    CrossrefPubMedGoogle Scholar
  • 87 Adlbrecht C, Bonderman D, Plass C. et al. Active endothelin is an important vasoconstrictor in acute coronary thrombi. Thromb Haemost 2007; 97: 642-649.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 88 Trial of abciximab with and without low-dose rete-plase for acute myocardial infarction. Strategies for Patency Enhancement in the Emergency Department (SPEED) Group Circulation. 2000 101. 2788-2794.
    PubMed
  • 89 Antman EM, Giugliano RP, Gibson CM. et al. Ab-ciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators. Circulation 1999; 99: 2720-2732.
    PubMedGoogle Scholar
  • 90 Topol EJ, GUSTO V. Investigators Reperfusion therapy for acute myocardial infarction with fibrino-lytic therapy or combination reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet 2001; 357: 1905-1914.
    CrossrefPubMedGoogle Scholar
  • 91 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.
    CrossrefPubMedGoogle Scholar
  • 92 Giugliano RP, Roe MT, Harrington RA. et al. IN-TEGRITI Investigators Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction: results of the inte-grilin and tenecteplase in acute myocardial infarction (INTEGRITI) Phase II Angiographic Trial. J Am Coll Cardiol 2003; 41: 1251-1260.
    CrossrefPubMedGoogle Scholar
  • 93 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.
    PubMedGoogle Scholar
  • 94 Combining thrombolysis with the platelet glyco-protein IIb/IIIa inhibitor lamifiban: results of the Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) trial. J Am Coll Cardiol 1998; 32: 2003-2010.
    CrossrefPubMedGoogle Scholar
  • 95 Sarullo FM, Pasquale PD, D'Alfonso G. et al. Safety and efficacy of thrombolysis with alteplase (50 mg) plus tirofiban versus alteplase (100 mg) alone in acute myocardial infarction: preliminary findings. Ital Heart J 2001; 02: 605-611.
    PubMedGoogle Scholar
  • 96 Ronner E, van Kesteren HA, Zijnen P. et al. Safety and efficacy of eptifibatide vs placebo in patients receiving thrombolytic therapy with streptokinase for acute myocardial infarction; a phase II dose escalation, randomized, double-blind study. Eur Heart J 2000; 21: 1530-1536.
    CrossrefPubMedGoogle Scholar
  • 97 Antman EM, Gibson CM, de Lemos JA. et al. Combination reperfusion therapy with abciximab and reduced dose reteplase: results from TIMI 14. The Thrombolysis in Myocardial Infarction (TIMI) 14 Investigators. Eur Heart J 2000; 21: 1944-1953.
    CrossrefPubMedGoogle Scholar
  • 98 Ohman EM, Va n, de Werf F, Antman EM. et al. FASTER (TIMI 24) Investigators Te necteplase and ti-rofiban in ST-segment elevation acute myocardial infarction: results of a randomized trial. Am Heart J 2005; 150: 79-88.
    CrossrefPubMedGoogle Scholar
  • 99 Stone G, Grines CL, Cox AD. et al. for the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators Comparison of angioplasty with stenting with or without abciximab, in acute myocardial infarction. N Engl J Med 2002; 346: 957-966.
    CrossrefPubMedGoogle Scholar
  • 100 Brener SJ, Ban LA, Burchenal JEB. et al. on the behalf of the RAPPORT investigators Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998; 98: 734-741.
    CrossrefPubMedGoogle Scholar
  • 101 Neumann FJ, Kastrati A, Schmitt C. et al. Effect of glycoprotein IIb/IIIa receptor blockade with abciximab on clinical and angiographic restenosis rate after the placement of coronary stents following acute myocardial infarction. J Am Coll Cardiol 2000; 35: 915-921.
    CrossrefPubMedGoogle Scholar
  • 102 Montalescot G, Barragan P, Wittemberg O. et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 2001; 344: 1895-1903.
    CrossrefPubMedGoogle Scholar
  • 103 Petronio AS, Musumeci G, Limbruno U. et al. Ab-ciximab improves 6-month clinical outcome after rescue coronary angioplasty. Am Heart J 2002; 143: 334-341.
    CrossrefPubMedGoogle Scholar
  • 104 Zorman S, Zorman D, Noc M. Effects of abciximab pretreatment in patients with acute myocardial infarction undergoing primary angioplasty. Am J Cardiol 2002; 90: 533-536.
    CrossrefPubMedGoogle Scholar
  • 105 Lee CW, Moon DH, Hong MK. et al. Effect of ab-ciximab on myocardial salvage in patients with acute myocardial infarction undergoing primary angioplasty. Am J Cardiol 2002; 90: 1243-1246.
    CrossrefPubMedGoogle Scholar
  • 106 Antoniucci D, Migliorini A, Parodi G. et al. Ab-ciximab-supported infarct artery stent implantation for acute myocardial infarction and long-term survival: a prospective, multicenter, randomized trial comparing infarct artery stenting plus abciximab with stenting alone. Circulation 2004; 109: 1704-1706.
    CrossrefPubMedGoogle Scholar
  • 107 Petronio AS, De Carlo M, Ciabatti N. et al. Left ventricular remodeling after primary coronary angio-plasty in patients treated with abciximab or intracoron-ary adenosine. Am Heart J 2005; 150: 1015.
    PubMedGoogle Scholar
  • 108 Steen H, Lehrke S, Wiegand UK. et al. Very early cardiac magnetic resonance imaging for quantification of myocardial tissue perfusion in patients receiving ti-rofiban before percutaneous coronary intervention for ST-elevation myocardial infarction. Am Heart J 2005; 149: 564.
    PubMedGoogle Scholar
  • 109 Ernst NM, Suryapranata H, Miedema K. et al. Achieved platelet aggregation inhibition after different antiplatelet regimens during percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Am Coll Cardiol 2004; 44: 1187-1193.
    CrossrefPubMedGoogle Scholar
  • 110 Bolognese L. Effects of pre-treatment with abciximab on coronary artery patency and microcirculation in high risk patients with acute myocardial infarction elegible for primary angioplasty: results of the Abciximab patients evaluation (APE) randomized pilot study. Circulation 2000; 10: 150 suppl A
    PubMedGoogle Scholar
  • 110 Bolognese L. Effects of pre-treatment with abciximab on coronary artery patency and microcirculation in high risk patients with acute myocardial infarction elegible for primary angioplasty: results of the Abciximab patients evaluation (APE) randomized pilot study. Circulation. 2000 10. 150 suppl A
    PubMedGoogle Scholar
  • 111 De Luca G, Smit JJ, Ernst N. et al. Impact of adjunctive tirofiban administration on myocardial perfusion and mortality in patients undergoing primary angioplasty for ST-segment elevation myocardial infarction. Thromb Haemost 2005; 93: 820-823.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 112 Danzi GB, Sesana M, Capuano C. et al. Comparison in patients having primary coronary angioplasty of abciximab versus tirofiban on recovery of left ventricular function. Am J Cardiol 2004; 94: 35-39.
    PubMedGoogle Scholar
  • 113 Valgimigli M, Percoco G, Malagutti P. et al. STRAT EGY Investigators Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial. J Am Med Assoc 2005; 293: 2109-2117.
    CrossrefPubMedGoogle Scholar
  • 114 Valgimigli M, Bolognese L, Anselmi M. et al. Tw o-by-two factorial comparison of high-bolus-dose tirofiban followed by standard infusion versus abcixi-mab and sirolimus-eluting versus bare-metal stent implantation in patients with acute myocardial infarction: design and rationale for the MULTI-STRATEGY trial. Am Heart J 2007; 154: 39-45.
    CrossrefPubMedGoogle Scholar
  • 115 Zeymer U. Abciximab vs Eptifibatide in primary PCI for acute ST - segment elevation myocardial infarction. EVA-AMI trial. http://scientificsessions.americanheart.org/includes/pdfs/03EVA_AMIshort.pdf
    PubMedGoogle Scholar
  • 116 Bellandi F, Maioli M, Gallopin M. et al. Increase of myocardial salvage and left ventricular function recovery with intracoronary abciximab downstream of the coronary occlusion in patients with acute myo-cardial infarction treated with primary coronary intervention. Catheter Cardiovasc Interv 2004; 62: 186-192.
    CrossrefPubMedGoogle Scholar
  • 117 Intracoronary Compared with Intravenous Bolus Abciximab Application in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Coronary Intervention. The randomized Leipzig Immadiate percutaneous Coronary InterventionAbciximab i.v. versus i.c. in ST-Elevation Myocardial Infarction Trial (LIP-SIAAbciximab-STEMI). Circulation. 2007 116. II-673 (Abstract)
    PubMedGoogle Scholar
  • 118 De Luca G, Suryapranata H, Stone GW. et al. Relationship between patient's risk profile and benefits in mortality from adjunctive abciximab to mechanical revascularization for ST-segment elevation myocardial infarction: a meta-regression analysis of randomized trials. J Am Coll Cardiol 2006; 47: 685-686.
    CrossrefPubMedGoogle Scholar
  • 119 Tolleson TR, O'Shea JC, Bittl JA. et al. Relationship between heparin anticoagulation and clinical outcomes in coronary stent intervention: observations from the ESPRIT trial. J Am Coll Cardiol 2003; 41: 386-393.
    PubMedGoogle Scholar
  • 120 Casserly IP, Topol EJ, Jia G. et al. Effect of abciximab versus tirofiban on activated clotting time during percutaneous intervention and its relation to clinical outcomes--observations from the TARGET trial. Am J Cardiol 2003; 92: 125-129.
    PubMedGoogle Scholar
  • 121 De Luca G, Suryapranata H, Ottervanger JP. et al. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation 2004; 109: 1223-1225.
    CrossrefPubMedGoogle Scholar
  • 122 De Luca G, van't HofAW, de Boer MJ. et al. Time-to-treatment significantly affects the extent of ST-segment resolution and myocardial blush in patients with acute myocardial infarction treated by primary angioplasty. Eur Heart J 2004; 25: 1009-1013.
    CrossrefPubMedGoogle Scholar
  • 123 Tarantini G, Cacciavillani L, Corbetti F. et al. Duration of ischemia is a major determinant of transmurality and severe microvascular obstruction after primary angioplasty: a study performed with contrast-enhanced magnetic resonance. J Am Coll Cardiol 2005; 46: 1229-1235.
    CrossrefPubMedGoogle Scholar
  • 124 Bednar F, Widimsky P, Krupicka J. et al. PRAGUE Study Group Investigators Interhospital transport for primary angioplasty improves the long-term outcome of acute myocardial infarction compared with immediate thrombolysis in the nearest hospital (one-year follow-up of the PRAGUE-1 study). Can J Cardiol 2003; 19: 1133-1137.
    PubMedGoogle Scholar
  • 125 De Luca G, Ernst N, Suryapranata H. et al. Relation of interhospital delay and mortality in patients with ST-segment elevation myocardial infarction transferred for primary coronary angioplasty. Am J Cardiol 2005; 95: 1361-1363.
    CrossrefPubMedGoogle Scholar
  • 126 van't Hof AW, Ernst N, de Boer MJ. et al. On-TIME study group Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial. Eur Heart J 2004; 25: 837-846.
    CrossrefPubMedGoogle Scholar
  • 127 Gibson CM, Kirtane AJ, Murphy SA. et al. TIMI Study Group 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.
    CrossrefPubMedGoogle Scholar
  • 128 Zeymer U, Zahn R, Schiele R. et al. Early eptifibatide improves TIMI 3 patency before primary percutaneous coronary intervention for acute ST elevation myocardial infarction: results of the randomized integrilin in acute myocardial infarction (INTA MI) pilot trial. Eur Heart J 2005; 26: 1971-1977.
    CrossrefPubMedGoogle Scholar
  • 129 Cutlip DE, Ricciardi MJ, Ling FS. et al. Effect of tirofiban before primary angioplasty on initial coronary flow and early ST - segment resolution in patients with acute myocardial infarction. Am J Cardiol 2003; 92: 977-980.
    CrossrefPubMedGoogle Scholar
  • 130 Lee DP, Herity NA, Hiatt BL. et al. TIrofiban Given in the Emergency Room before Primary Angio-plasty Adjunctive platelet glycoprotein IIb/IIIa receptor inhibition with tirofiban before primary angioplasty improves angiographic outcomes: results of the TIrofiban Given in the Emergency Room before PrimaryAngioplasty (TIGER-PA) pilot trial. Circulation 2003; 107: 1497-1501.
    CrossrefPubMedGoogle Scholar
  • 131 Maioli M, Bellandi F, Leoncini M. et al. Randomized early versus late abciximab in acute myocardial infarction treated with primary coronary intervention (RELAx-AMI Trial). J Am Coll Cardiol 2007; 49: 1517-1524.
    CrossrefPubMedGoogle Scholar
  • 132 Arntz HR, Schroder J, Schwimmbeck P. et al. Is early prehospital administration of abciximab superior to periprocedural therapy in patients with STEMI and planned PCI? Early and late results from the randomized REOMOBILE Pilot study. JACC 2004; 43 suppl A 256.
    PubMedGoogle Scholar
  • 133 Gabriel HM, Oliveira JA, da Silva PC. et al. Early administration of abciximab bolus in the emergency department improves angiographic outcome after primary PCI as assessed by TIMI frame count: results of the early ReoPro administration in myocardial infarction (ERAMI) trial. Catheter Cardiovasc Interv 2006; 68: 218-224.
    CrossrefPubMedGoogle Scholar
  • 134 Gyongyosi M, Domanovits H, Benzer W. et al. Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion - results of the Austrian multi-centre randomized ReoPro-BRIDGING Study. Eur Heart J 2004; 25: 2125-2133.
    CrossrefPubMedGoogle Scholar
  • 135 Rakowski T, Zalewski J, Legutko J. et al. Early abciximab administration before primary percutaneous coronary intervention improves infarct-related artery patency and left ventricular function in high-risk patients with anterior wall myocardial infarction: a randomized study. Am Heart J 2007; 153: 360-365.
    CrossrefPubMedGoogle Scholar
  • 136 Emre A, Ucer E, Yesilcimen K. et al. Impact of early tirofiban on myocardial salvage in patients with acute myocardial infarction undergoing infarct-related artery stenting. Cardiology 2006; 106: 264-269.
    CrossrefPubMedGoogle Scholar
  • 137 Ellis S. The FINESSE Trial (Facilitated INtervention with Enhanced Reperfusion Speedto Stop Events. http://www.escardio.org/congresses/esc_congress/esc2007/news/HLIIFinesseEllisVDWerf.htm
    PubMedGoogle Scholar
  • 138 Dudek D, Siudak Z, Janzon M. et al. Patients transferred for primary PCI display reduced mortality when treatment with abciximab was started early compared with abciximab given in the cathlab. Results from the EUROTRANSFER Registry. European Heart J. 2007 28. (Suppl): 384 Abstract.
    PubMedGoogle Scholar
  • 139 Huber K, Aylward PE, van’t Hof AWJ. et al. Glycoprotein IIb-IIIa inhibitors before primary percutaneous coronary intervention of ST - Elevation myocardial infarction improve perfusion and outcomes: Insights from APEX-AMI. Circulation. 2007 116. II-673 Abstract.
    PubMedGoogle Scholar
  • 140 Kastrati A, Mehilli J, Schlotterbeck K. et al. Bavarian Reperfusion Alternatives Evaluation (BRAVE) Study Investigators Early administration of reteplase plus abciximab vs abciximab alone in patients with acute myocardial infarction referred for percutaneous coronary intervention: a randomized controlled trial. J Am Med Assoc 2004; 291: 947-954.
    CrossrefPubMedGoogle Scholar
  • 141 Wo ngA, Mak KH, Chan C. et al. Combined fibrinolysis using reduced-dose alteplase plus abciximab with immediate rescue angioplasty versus primary an-gioplasty with adjunct use of abciximab for the treatment of acute myocardial infarction: Asia-Pacific Acute Myocardial Infarction Trial (APAMIT) pilot study. Catheter Cardiovasc Interv 2004; 62: 445-452.
    CrossrefPubMedGoogle Scholar
  • 142 ADV A NCE MI Investigators. Facilitated percutaneous coronary intervention for acute ST - segment elevation myocardial infarction: results from the prematurely terminated ADdressing the Value of facilitated ANgioplasty after Combination therapy or Eptifi-batide monotherapy in acute Myocardial Infarction (ADVA NCE MI) trial. Am Heart J. 2005 150. 116-122.
    PubMedGoogle Scholar
  • 143 Taher T, Fu Y, Wagner GS. et al. Aborted myo-cardial infarction in patients with ST-segment elevation: insights from the Assessment of the Safety and Efficacy of a New Thrombolytic Regimen-3Trial Elec-trocardiographic Substudy. J Am Coll Cardiol 2004; 44: 38-43.
    CrossrefPubMedGoogle Scholar
  • 144 Savonitto S, Armstrong PW, Lincoff AM. et al. Risk of intracranial haemorrhage with combined fibri-nolytic and glycoprotein IIb/IIIa inhibitor therapy in acute myocardial infarction. Dichotomous response as a function of age in the GUSTO V trial. Eur Heart J 2003; 24: 1807-1814.
    CrossrefPubMedGoogle Scholar