Skip to main content
SpringerLink
Log in

Frühe Antiplättchentherapie und Gerinnungshemmung bei akutem Koronarsyndrom

Hintergrund und aktuelle Studienlage

Early antiplatelet therapy and anticoagulation for acute coronary syndrome: Background and recent studies

  • Leitthema
  • Published:
Notfall + Rettungsmedizin Aims and scope Submit manuscript

Zusammenfassung

Die antithrombozytäre und antikoagulatorische Therapie bei akutem Koronarsyndrom (AKS) entwickelt sich mit kaum noch zu überblickender Dynamik als Folge der Verfügbarkeit neuer Substanzen, neuer Kombinationen und neuer Therapiestrategien. Die vielfältigen möglichen Kombinationen gerinnungshemmender Pharmaka sind noch lange nicht alle erprobt und bieten Chancen zu weiterem Fortschritt. Demgegenüber steht das Problem eines steigenden Blutungsrisikos, das in vielen Fällen den Nutzen hinsichtlich der Vermeidung insbesondere früher koronarer Rezidivereignisse zumindest teilweise aufzuheben droht. Besonders stark erhöhte Blutungsrisiken fanden sich z. B. beim Einsatz von Glykoprotein-IIb/IIIa-Rezeptorblockern in Kombination mit Thrombolytika (v. a. Streptokinase) oder hochdosiertem Enoxaparin bei älteren weiblichen Patienten mit geringem Körpergewicht. Im Gegensatz dazu steigert Clopidogrel in der Akuttherapie die Blutungsrisiken wenn überhaupt nur unwesentlich und ist auch langfristig eine Schlüsseltherapie bei AKS. Vorsichtige Therapieansätze mit reduzierten, risikoangepassten Dosierungen bei Patienten über 75 Jahren und solchen mit deutlich eingeschränkter Nierenfunktion, die beispielhaft in der EXTRACT-TIMI-25-Studie für Enoxaparin gezeigt werden, sind geeignet, den langen Weg bis zu einer optimalen gerinnungshemmenden Behandlung bei akutem Koronarsyndrom zu sichern.

Abstract

Antiplatelet and antithrombin treatment for patients suffering from acute coronary syndrome is dynamically developing with increasing speed due to new agents, new combinations and new therapeutic strategies. Many combinations of anticoagulants and antiplatelets have not yet been tested and may offer new chances for therapeutic success. These chances are opposed by an increasing bleeding risk which may at least partially abolish the advantages achieved with more aggressive treatment targeting to avoid early adverse coronary events. Bleeding is profoundly elevated with the combination of Glycoprotein IIb/IIIa receptor blockers and thrombolytics, notably streptokinase. Also high dose enoxaparin leads to more major hemorrhages when given to elderly female patients with low body weight. In contrast, clopidogrel does not increase bleeding risk or if at all only to a minimal extent, thus becoming a key medication for patients presenting with signs of an acute coronary syndrome. Cautious treatment strategies with risk-adjusted dosing e.g. in elderly patients over 75 years of age and patients with renal impairment as exemplary executed in the ExTRACT-TIMI 25 study show the way to optimal and safe anticoagulation therapy for patients with an acute coronary syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2

Literatur

  1. Arntz HR, Bossaert L, Filipatos GS (2005) European Resuscitation Council guidelines for resuscitation 2005. Section 5. Initial management of acute coronary syndromes. Resuscitation (Suppl I) 67: S87–S96

  2. Bassand JP, Hamm CW, Ardissino D et al. (2007) Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. Eur Heart J 28: 1598–1660

    Article  PubMed  CAS  Google Scholar 

  3. European Society of Cardiology (2000) Myocardial infarction redefined – a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 36: 959–969

    Article  Google Scholar 

  4. Hamm C, Arntz HR, Bode C et al. (2004) Leitlinien: Akutes Koronarsyndrom (ACS) Teil 1: ACS ohne persistierende ST-Hebung. Z Kardiol 93: 72–90

    Article  PubMed  CAS  Google Scholar 

  5. Hamm C, Arntz HR, Bode C et al. (2004) Leitlinien: Akutes Koronarsyndrom (ACS) Teil 2: ACS mit ST-Hebung. Z Kardiol 93: 324–341

    Article  PubMed  CAS  Google Scholar 

  6. Task Force Report (2003) Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 24: 28–66

    Google Scholar 

  7. Bovill EG, Terrin ML, Stump DC et al. (1991) Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial. Ann Intern Med 115: 256–265

    PubMed  CAS  Google Scholar 

  8. Moscucci M, Fox KA, Cannon CP et al. (2003) Predictors of major bleeding in acute coronary syndromes: the Global Registry of Acute Coronary Events (GRACE). Eur Heart J 24: 1815–1823

    Article  PubMed  CAS  Google Scholar 

  9. Rao SV, O’Grady K, Pieper KS et al. (2005) Impact of bleeding severity on clinical outcomes among patients with acute coronary syndromes. Am J Cardiol 96: 1200–1206

    Article  PubMed  Google Scholar 

  10. Spinler SA, Inverso SM, Cohen M et al. ESSENCE and TIMI 11B Investigators (2003) Safety and efficacy of unfractionated heparin versus enoxaparin in patients who are obese and patients with severe renal impairment: analysis from the ESSENCE and TIMI 11B studies. Am Heart J 146: 33–41

    Article  PubMed  CAS  Google Scholar 

  11. Boersma E, Harrington RA, Moliterno DJ et al. (2002) Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 359: 189–198

    Article  PubMed  CAS  Google Scholar 

  12. GUSTO IV-ACS Investigators (2001) 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 357: 1915–1924

    Article  Google Scholar 

  13. Stone GW, Bertrand ME, Moses JW et al. ACUITY Investigators (2007) Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial. JAMA 297: 591–602

    Article  PubMed  CAS  Google Scholar 

  14. Silber S, Albertsson P, Aviles FF et al. Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology (2005) Guidelines for percutaneous coronary interventions. Eur Heart J 26: 804–847

    Article  PubMed  Google Scholar 

  15. Ferguson JJ, Califf RM, Antman EM et al. SYNERGY Trial Investigators (2004) Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 292: 45–54

    Article  PubMed  CAS  Google Scholar 

  16. Petersen JL, Mahaffey KW, Hasselblad V et al. (2004) Efficacy and bleeding complications among patients randomized to Enoxaparin or infractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes. a systematic overview. JAMA 292: 89–96

    Article  PubMed  CAS  Google Scholar 

  17. Müller I, Besta F, Schulz C et al. (2003) Effects of statins on platelet inhibition by a high loading dose of clopidogrel. Circulation 108: 2195–2197

    Article  PubMed  CAS  Google Scholar 

  18. Müller I, Seyfarth M, Rudiger S et al. (2001) Effect of a high loading dose of clopidogrel on platelet function in patients undergoing coronary stent placement. Heart 85: 92–93

    Article  PubMed  Google Scholar 

  19. Montalescot G, Sideris G, Meuleman C et al. ALBION Trial Investigators (2006) 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 48: 31–38

    Article  CAS  Google Scholar 

  20. Wiviott SD, Antman EM, Gibson CM et al. TRITON-TIMI 38 Investigators (2006) Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel thrombolysis in myocardial infarction 38 (TRITON-TIMI 38). Am Heart J 152: 627–635

    Article  PubMed  CAS  Google Scholar 

  21. CAPRIE Steering Committee (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 348: 1329–1339

    Article  Google Scholar 

  22. Yusuf S, Zhao F, Mehta SR et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators (2001) Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 345: 494–502

    Article  PubMed  CAS  Google Scholar 

  23. Mehta SR, Yusuf S, Peters RJ et al. Clopidogrel in Unstable angina to prevent Recurrent Events trial (CURE) Investigators (2001) Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 358: 527–533

    Article  PubMed  CAS  Google Scholar 

  24. Fox KA, Mehta SR, Peters R et al. Clopidogrel in Unstable angina to prevent Recurrent ischemic Events Trial (2004) 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 110: 1202–1208

    Article  PubMed  CAS  Google Scholar 

  25. Steinhubl SR, Berger PB, Mann JT 3rd et al. CREDO Investigators (2002) Clopidogrel for the Reduction of Events During Observation. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA 288: 2411–2420

    Article  PubMed  CAS  Google Scholar 

  26. Patti G, Colonna G, Pasceri V et al. (2005) 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 111: 2099–2106

    Article  PubMed  CAS  Google Scholar 

  27. Neumann FJ, Kastrati A, Pogatsa-Murray G et al. (2003) Evaluation of prolonged antithrombotic pretreatment („cooling-off“ strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA 290: 1593–1599

    Article  PubMed  CAS  Google Scholar 

  28. Kastrati A, Mehilli J, Schühlen H et al. (2004) A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel. N Engl J Med 350: 232–238

    Article  PubMed  CAS  Google Scholar 

  29. Kastrati A, Mehilli J, Neumann FJ et al. Intracoronary Stenting and Antithrombotic: Regimen Rapid Early Action for Coronary Treatment 2 (ISAR-REACT 2) Trial Investigators (2006) Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial. JAMA 295: 1531–1538

    Article  PubMed  CAS  Google Scholar 

  30. Maisel WH (2007) Unanswered questions – drug-eluting stents and the risk of late thrombosis. N Engl J Med 356: 981–984

    Article  PubMed  CAS  Google Scholar 

  31. Iakovou I, Schmidt T, Bonizzoni E et al. (2005) Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 293: 2126–2130

    Article  PubMed  CAS  Google Scholar 

  32. Théroux P, Ouimet H, McCans J et al. (1988) Aspirin, Heparin, or both to treat acute unstable angina. N Engl J Med 319: 1105–1111

    Article  PubMed  Google Scholar 

  33. The RISC Group (1990) Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet 336: 827–830

    Article  Google Scholar 

  34. Wallentin L, Lagerquist B, Husted S et al. (2000) Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation during Instability in Coronary artery disease. Lancet 356: 9–16

    Article  PubMed  CAS  Google Scholar 

  35. Leizorovicz A (1998) The FRAXIS Investigators. XXth Congress of the European Society of Cardiology, Vienna, Austria

  36. Antman EM, Cohen M, McCabe C et al. (2002) Enoxaparin is superior to unfractionated heparin for preventing clinical events at 1-year follow-up of TIMI 11B and ESSENCE. Eur Heart J 23: 308–314

    Article  PubMed  CAS  Google Scholar 

  37. Antman EM, McCabe CH, Gurfinkel EP et al. (1999) Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction. Circulation 100: 1593–1601

    PubMed  CAS  Google Scholar 

  38. Petersen JL, Mahaffey KW, Hasselblad V et al. (2004) Efficacy and bleeding complications among patients randomized to Enoxaparin or infractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes. a systematic overview. JAMA 292: 89–96

    Article  PubMed  CAS  Google Scholar 

  39. Ferguson JJ, Califf RM, Antman EM et al. SYNERGY Trial Investigators (2004) Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA 292: 45–54

    Article  PubMed  CAS  Google Scholar 

  40. Mahaffey KW, Cohen M, Garg J et al. SYNERGY Trial Investigators (2005) High-risk patients with acute coronary syndromes treated with low-molecular-weight or unfractionated heparin: outcomes at 6 months and 1 year in the SYNERGY trial. JAMA 294: 2594–2600

    Article  PubMed  CAS  Google Scholar 

  41. Borentain M, Montalescot G, Bouzamondo A et al. (2005) Low-molecular-weight heparin vs. unfractionated heparin in percutaneous coronary intervention: a combined analysis. Catheter Cardiovasc Interv 65: 212–221

    Article  PubMed  Google Scholar 

  42. Montalescot G, White HD, Gallo R et al. STEEPLE Investigators (2006) Enoxaparin versus unfractionated heparin in elective percutaneous coronary intervention. N Engl J Med 355: 1006–1017

    Article  PubMed  CAS  Google Scholar 

  43. Simoons ML, Bobbink IW, Boland J et al. PENTUA Investigators (2004) A dose-finding study of fondaparinux in patients with non-ST-segment elevation acute coronary syndromes: the Pentasaccharide in Unstable Angina (PENTUA) Study. J Am Coll Cardiol 43: 2183–2190

    Article  PubMed  CAS  Google Scholar 

  44. Mehta SR, Steg PG, Granger CB et al. ASPIRE Investigators (2005) Randomized, blinded trial comparing fondaparinux with unfractionated heparin in patients undergoing contemporary percutaneous coronary intervention: Arixtra Study in Percutaneous coronary Intervention: a Randomized Evaluation (ASPIRE) Pilot Trial. Circulation 111: 1390–1397

    Article  PubMed  CAS  Google Scholar 

  45. Yusuf S, Mehta SR, Chrolavicius S et al. (2006) Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 354: 1464–1476

    Article  PubMed  CAS  Google Scholar 

  46. Lincoff AM, Kleiman NS, Kereiakes DJ et al. REPLACE-2 Investigators (2004) Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial. JAMA 292: 696–703

    Article  PubMed  CAS  Google Scholar 

  47. Stone GW, McLaurin BT, Cox DA et al. ACUITY Investigators (2006) Bivalirudin for patients with acute coronary syndromes. N Engl J Med 355: 2203–2216

    Article  PubMed  CAS  Google Scholar 

  48. Stone GW, White HD, Ohman EM et al. Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial investigators (2007) Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. Lancet 369: 907–919

    Article  PubMed  CAS  Google Scholar 

  49. Antman EM, Anbe DT, Armstrong PW et al. American Heart Association, Canadian Cardiovascular Society (2004) ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction – executive summary. J Am Coll Cardiol 44: 671–719

    Article  PubMed  Google Scholar 

  50. Hochman JS, Sleeper LA, Webb JG et al. (1999) Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should we emergently revascularize occluded coronaries for cardiogenic shock. N Engl J Med 341: 625–634

    Article  PubMed  CAS  Google Scholar 

  51. Gersh BJ, Antman EM (2006) Selection of the optimal reperfusion strategy for STEMI: does time matter? Eur Heart J 27: 761–763

    Article  PubMed  Google Scholar 

  52. Keeley EC, Boura JA, Grines CL (2006) Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials. Lancet 367: 579–588

    Article  PubMed  CAS  Google Scholar 

  53. Assessment of the Safety and Efficacy of a New Treatment Strategy with Percutaneous Coronary Intervention (ASSENT-4 PCI) investigators (2006) Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet 367: 569–578

    Article  CAS  Google Scholar 

  54. Fernandez-Aviles F, Alonso JJ, Castro-Beiras A et al. GRACIA (Grupo de Analisis de la Cardiopatia Isquemica Aguda) Group (2004) Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial. Lancet 364: 1045–1053

    Article  PubMed  Google Scholar 

  55. Scheller B, Hennen B, Hammer B et al. SIAM III Study Group (2003) Beneficial effects of immediate stenting after thrombolysis in acute myocardial infarction. J Am Coll Cardiol 42: 634–641

    Article  PubMed  Google Scholar 

  56. Neumann FJ, Kastrati A, Schmitt C et al. (2000) 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 35: 915–921

    Article  PubMed  CAS  Google Scholar 

  57. Montalescot G, Barragan P, Wittenberg O et al. (2001) Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med 344: 1895–1903

    Article  PubMed  CAS  Google Scholar 

  58. Stone GW, Grines CL, Cox DA et al. Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Investigators (2002) Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction. N Engl J Med 346: 957–966

    Article  PubMed  CAS  Google Scholar 

  59. Hof AW van’t, Ernst N, Boer MJ de et al. On-TIME study group (2004) 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 25: 837–846

    Article  CAS  Google Scholar 

  60. Zeymer U, Zahn R, Schiele R et al. (2005) 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 (INTAMI) pilot trial. Eur Heart J 26: 1971–1977

    Article  PubMed  CAS  Google Scholar 

  61. Gibson CM, Kirtane AJ, Murphy SA et al. TIMI Study Group (2006) 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 152: 668–675

    Article  PubMed  CAS  Google Scholar 

  62. Gyöngyösi M, Domanovits H, Benzer W et al. ReoPro-BRIDGING Study Group (2004) 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 25: 2125–2133

    Article  PubMed  CAS  Google Scholar 

  63. Lee DP, Herity NA, Hiatt BL et al. TIrofiban Given in the Emergency Room before Primary Angioplasty (2003) 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 Primary Angioplasty (TIGER-PA) pilot trial. Circulation 107: 1497–1501

    Article  PubMed  Google Scholar 

  64. Montalescot G, Borentain M, Payot L et al. (2004) Early vs late administration of glycoprotein IIb/IIIa inhibitors in primary percutaneous coronary intervention of acute ST-segment elevation myocardial infarction: a meta-analysis. JAMA 292: 362–366

    Article  PubMed  CAS  Google Scholar 

  65. Antman EM, Giugliano RP, Gibson CM et al. (1999) Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. Circulation 99: 2720–2732

    PubMed  CAS  Google Scholar 

  66. Topol EJ, The GUSTO V Investigators (2001) 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 357: 1905–1914

    Article  PubMed  CAS  Google Scholar 

  67. Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators (2001) Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 358: 605–613

    Article  Google Scholar 

  68. Ellis SG, Armstrong P, Betriu A et al. Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events Investigators (2004) Facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention: design and rationale of the Facilitated Intervention with Enhanced Reperfusion Speed to Stop Events (FINESSE) trial. Am Heart J 147: E16

    Article  PubMed  Google Scholar 

  69. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group (1988) Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet ii: 349–360

    Google Scholar 

  70. Zijlstra F, Ernst N, Boer MJ de et al. (2002) Influence of prehospital administration of aspirin and heparin on initial patency of the infarct-related artery in patients with acute ST elevation myocardial infarction. J Am Coll Cardiol 39: 1733–1737

    Article  PubMed  CAS  Google Scholar 

  71. Chen ZM, Jiang LX, Chen YP et al. COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group (2005) Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet 366: 1607–1621

    Article  PubMed  CAS  Google Scholar 

  72. Sabatine MS, Cannon CP, Gibson CM et al. CLARITY-TIMI 28 Investigators (2005) Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 352: 1179–1189

    Article  PubMed  CAS  Google Scholar 

  73. Verheugt FW, Montalescot G, Sabatine MS et al. (2007) Prehospital fibrinolysis with dual antiplatelet therapy in ST-elevation acute myocardial infarction: a substudy of the randomized double blind CLARITY-TIMI 28 trial. J Thromb Thrombolysis 23: 173–179

    Article  PubMed  CAS  Google Scholar 

  74. Gibson CM, Ly HQ, Murphy SA et al. TIMI Study Group (2006) Usefulness of clopidogrel in abolishing the increased risk of reinfarction associated with higher platelet counts in patients with ST-elevation myocardial infarction (results from CLARITY-TIMI 28). Am J Cardiol 98: 761–763

    Article  PubMed  CAS  Google Scholar 

  75. Sabatine MS, Cannon CP, Gibson CM et al. Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators (2005) Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 294: 1224–1232

    Article  PubMed  CAS  Google Scholar 

  76. Scirica BM, Sabatine MS, Morrow DA et al. (2006) The role of clopidogrel in early and sustained arterial patency after fibrinolysis for ST-segment elevation myocardial infarction: the ECG CLARITY-TIMI 28 Study. J Am Coll Cardiol 48: 37–42

    Article  PubMed  CAS  Google Scholar 

  77. Zeymer U, Arntz HR, Darius H et al. (2006) Efficacy and safety of clopidogrel 600 mg administered pre-hospitally to improve primary percutaneous coronary intervention in patients with acute myocardial infarction (CIPAMI): Study rationale and design. Cardiology 108: 265–272

    Article  PubMed  CAS  Google Scholar 

  78. Liem A, Zijlstra F, Ottervanger JP et al. (2000) High dose heparin as pretreatment for primary angioplasty in acute myocardial infarction: the Heparin in Early Patency (HEAP) randomized trial. J Am Coll Cardiol 35: 600–604

    Article  PubMed  CAS  Google Scholar 

  79. The GUSTO Investigators (1993) An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med 329: 703–709

    Article  Google Scholar 

  80. Frostfeldt G, Ahlberg G, Gustafsson G et al. (1999) Low molecular weight heparin (dalteparin) as adjuvant treatment of thrombolysis in acute myocardial infarction–a pilot study: biochemical markers in acute coronary syndromes (BIOMACS II). J Am Coll Cardiol 33: 627–633

    Article  PubMed  CAS  Google Scholar 

  81. Ross AM, Molhoek P, Lundergan C et al. HART II Investigators (2001) 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 and Aspirin Reperfusion Therapy (HART II). Circulation 104: 648–652

    Article  PubMed  CAS  Google Scholar 

  82. Antman EM, Louwerenburg HW, Baars HF et al. (2002) Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction: results of the ENTIRE-Thrombolysis in Myocardial Infarction (TIMI) 23 Trial. Circulation 105: 1642–1649

    Article  PubMed  CAS  Google Scholar 

  83. Wallentin L, Goldstein P, Armstrong PW et al. (2003) 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 108: 135–142

    Article  PubMed  CAS  Google Scholar 

  84. Antman EM, Morrow DA, McCabe CH et al. ExTRACT-TIMI 25 Investigators (2006) Enoxaparin versus unfractionated heparin with fibrinolysis for ST-elevation myocardial infarction. N Engl J Med 354: 1477–1488

    Article  PubMed  CAS  Google Scholar 

  85. Sabatine MS, Morrow DA, Dalby A et al. ExTRACT-TIMI 25 Investigators (2007) Efficacy and safety of enoxaparin versus unfractionated heparin in patients with ST-segment elevation myocardial infarction also treated with clopidogrel. J Am Coll Cardiol 49: 2256–2263

    Article  PubMed  CAS  Google Scholar 

  86. Gibson CM, Murphy SA, Montalescot G et al. for the Extract TIMI 25 Investigators (2007) Percutaneous coronary intervention in patients receiving enoxaparin or unfractionated heparin after fibrinolytic therapy for ST-Segment elevation myocardial Infarction in the ExTRACT-TIMI 25 Trial. J Am Coll Cardiol (in press)

  87. Sabatine MS, Morrow DA, Montalescot G et al. Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) 28 Investigators (2005) Angiographic and clinical outcomes in patients receiving low-molecular-weight heparin versus unfractionated heparin in ST-elevation myocardial infarction treated with fibrinolytics in the CLARITY-TIMI 28 Trial. Circulation 112: 3846–3854

    Article  PubMed  CAS  Google Scholar 

  88. Coussement PK, Bassand JP, Convens C et al. PENTALYSE investigators (2001) A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study. Eur Heart J 22: 1716–1724

    Article  PubMed  CAS  Google Scholar 

  89. Yusuf S, Mehta SR, Chrolavicius S et al. OASIS-6 Trial Group (2006) Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA 295: 1519–1530

    Article  PubMed  CAS  Google Scholar 

  90. Zeymer U, Schroder R, Tebbe U et al. (2001) Non-invasive detection of early infarct vessel patency by resolution of ST-segment elevation in patients with thrombolysis for acute myocardial infarction; results of the angiographic substudy of the Hirudin for Improvement of Thrombolysis (HIT)-4 trial. Eur Heart J 22: 769–775

    Article  PubMed  CAS  Google Scholar 

  91. White H, Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators (2001) Thrombin-specific anticoagulation with bivalirudin versus heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet 358: 1855–1863

    Article  PubMed  CAS  Google Scholar 

  92. Dauerman HL, Frederick PD, Miller D, French WJ for the National Registry of Myocardial Infarction-5 Investigators (2007) Current incidence and clinical outcomes of bivalirudin administration among patients undergoing primary coronary intervention for stent thrombosis elevation acute myocardial infarction. Coron Artery Dis 18: 141–148

    Article  PubMed  Google Scholar 

  93. Arntz HR, Bossaert L, Fillipatos G (2006) Initiales Management von Patienten mit akutem Koronarsyndrom. Abschnitt 5 der Leitlinien zur Reanimation 2005 des European Resuscitation Council. Notfall Rettungsmed 9: 81–89

    Article  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin:

Referentenhonorare von Daiichi-Sankyo, Boehringer-Ingelheim, Sanofi-Aventis, MSD, Bristol-Myers Squibb.

Author information

Authors and Affiliations

  1. Medizinische Klinik II, Kardiologie und Pulmologie, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Deutschland

    H.R. Arntz

Authors
  1. H.R. Arntz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H.R. Arntz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Arntz, H. Frühe Antiplättchentherapie und Gerinnungshemmung bei akutem Koronarsyndrom. Notfall Rettungsmed 10, 500–510 (2007). https://doi.org/10.1007/s10049-007-0939-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10049-007-0939-y

Schlüsselwörter

Keywords

Search

Navigation