Download PDF
Hamostaseologie 2002; 22(04): 174-177
DOI: 10.1055/s-0037-1619556
Research Articles
Schattauer GmbH

Kombination von Antikoagulanzien und Plättchenfunktionshemmern

Combination therapy with anticoagulants and platelet-active drugs
A.-A. Weber
1   Institut für Pharmakologie und Klinische Pharmakologie, Universitätsklinikum Düsseldorf
› Author Affiliations
Further Information

Publication History

Publication Date:
27 December 2017 (online)

Also available at
    Permissions and Reprints

Zusammenfassung

Thrombozyten und Blutgerinnung dürfen nicht isoliert betrachtet werden. Beide Systeme werden bei einer Gefäßverletzung aktiviert und interagieren über verschiedene Mechanismen miteinander. Vor diesem Hintergrund sind bei der Kombination von Antikoagulanzien und Thrombozytenfunktionshemmern hämostaseologisch relevante Arzneimittelinteraktionen zu erwarten. Dazu gehören die synergistische Verstärkung der antithrombotischen Wirkung aber potenziell auch die synergistische Verstärkung der Blutungskomplikationen. In dieser kurzen Übersicht wird die klinische Wirksamkeit der Kombination von Antikoagulanzien und Thrombozytenfunktionshemmern bei Patienten mit akuten Koronarsyndromen (instabile Angina pectoris, Myokardinfarkt) diskutiert.

Summary

Platelets and the coagulation system cannot be regarded as completely separate systems. Both systems become activated upon vessel injury and multiple functional interactions exist. Thus with a combination therapy with anticoagulants and platelet-active drugs, drug interactions relevant for hemostasis must be expected. This includes a synergistic inhibition of the hemostatic system but also possible synergistic effects on bleeding complications. This concise review discusses the clinical efficacy of a combination therapy with anticoagulants and platelet-active drugs in patients with acute coronary syndromes (unstable angina, myocardial infarction).

Schlüsselwörter

Antikoagulanzien - Thrombozytenfunktionshemmer - Arzneimittelinteraktionen

Keywords

Anticoagulants - platelet-active drugs - drug interactions
 

  • Literatur

  • 1 Aguirre F, Ferguson JJ, Califf RM. for the EPIC Investigators. Clinical predictors of bleeding complications in high risk angioplasty: results from the EPIC Study Group. Circulation 1993; 88 (Suppl I): 1-252.
    PubMedGoogle Scholar
  • 2 Anand SS, Yusuf S. Oral anticoagulant therapy in patients with coronary artery disease: a meta-analysis. JAMA 1999; 282: 2058-67.
    CrossrefPubMedGoogle Scholar
  • 3 Brouwer MA, Verheugt FWA. Oral anticoagulation for acute coronary syndromes. Circulation 2002; 105: 1270-4.
    CrossrefPubMedGoogle Scholar
  • 4 Brouwer MA, van den Bergh PJPC, Aengevaeren WRM, Veen G, Luijten HE, Hertzberger DP, van Boven AJ, Vromans RPJW, Uijen GJH, Verheugt FWA. Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial. Circulation 2002; 106: 659-65.
    CrossrefPubMedGoogle Scholar
  • 5 Collins R, MacMahon S, Flather M, Remvig L, Mortensen S, Appleby P, Godwin J, Yusuf S, Peto R. Clinical effects of anticoagulant therapy in suspected acute myocardial infarction: systematic overview of randomized trials. Brit Med J 1996; 313: 652-9.
    CrossrefPubMedGoogle Scholar
  • 6 Collins R, Peto R, Baigent C, Sleight P. Aspirin, heparin, and fibrinolytic therapy in suspected acute myocardial infarction. N Engl J Med 1997; 336: 847-60.
    CrossrefPubMedGoogle Scholar
  • 7 Dale J, Myhre E, Loew D. Bleeding during acetylsalicylic acid and anticoagulant therapy in patients with reduced platelet reactivity after aortic valve replacement. Am Heart J 1980; 99: 746-51.
    CrossrefPubMedGoogle Scholar
  • 8 Fragmin and Fast Revascularization during Instability in Coronary Artery Disease Investigators. Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999; 354: 701-7.
    CrossrefPubMedGoogle Scholar
  • 9 Harrington RA, Kleiman NS, Kottke Marchant K, Lincoff AM, Tcheng JE, Sigmon KN, Joseph D, Rios G, Trainor K, Rose D. Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/ IIIa inhibitor during percutaneous intervention. Am J Cardiol 1995; 76: 1222-7.
    CrossrefPubMedGoogle Scholar
  • 10 Hirsh J, Dalen JE, Anderson DR, Poller L, Bussey H, Ansell J, Deykin D. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001; 119: 8S-21S.
    CrossrefPubMedGoogle Scholar
  • 11 Hirsh J, Anand SS, Halperin JL, Fuster V. Guide to anticoagulant therapy: heparin. Circulation 2001; 103: 2994-3018.
    CrossrefPubMedGoogle Scholar
  • 12 Hohlfeld T. Hämostasestörungen durch Analgetika, Antiphlogistika und Antirheumatika. Hämostaseologie 2001; 21: 22-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Hurlen M, Abdelnoor M, Smith P, Erikssen J, Arnesen H. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 247: 969-74.
    PubMedGoogle Scholar
  • 14 Lincoff AM, Tcheng JE, Califf RM, Bass T, Popma JJ, Teirstein PS, Kleiman NS, Hattel LJ, Anderson HV, Ferguson JJ, Cabot CF, Anderson KM, Berdan LG, Musco MH, Weisman HF, Topol EJ. Standard versus low-dose weight-adjusted heparin in patients treated with the platelet glycoprotein IIb/IIIa receptor antibody fragment abciximab (c7E3 Fab) during percutaneous coronary revascularization. Am J Cardiol 1997; 79: 286-91.
    CrossrefPubMedGoogle Scholar
  • 15 Kleiman NS, Tracy RP, Talley JD, Sigmon K, Joseph D, Topol EJ, Califf RM, Kitt M, Ohman EM. Inhibition of platelet aggregation with a glycoprotein IIb/IIIa antagonist does not prevent thrombin generation in patients undergoing thrombolysis for acute myocardial infarction. J Thromb Thrombol 2000; 9: 5-12.
    PubMedGoogle Scholar
  • 16 Ofosu A, Longbin L, Freedman J. Control mechanisms in thrombin generation. Sem Thromb Hemost 1996; 22: 303-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Oler A, Whooley MA, Oler J, Grady D. Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina: a meta-analysis. JAMA 1996; 276: 811-5.
    CrossrefPubMedGoogle Scholar
  • 18 Reverter JC, Bèguin S, Kessels H, Kumar R, Hemker HC, Coller BS. Inhibition of platelet-mediated, tissue factor-induced thrombin generation by the mouse/human chimeric 7E3 antibody: potential implications for the effect of c7E3 Fab treatment on acute thrombosis and „clinical restenosis“. J Clin Invest 1996; 98: 863-74.
    CrossrefPubMedGoogle Scholar
  • 19 Schulman S, Henriksson K. Interaction of ibuprofen and warfarin on primary hemostasis. Br J Rheumatol 1989; 38: 46-9.
    PubMedGoogle Scholar
  • 20 Tcheng JE, Harrington RA, Kottke-Marchant K, Kleiman NS, Ellis SG, Kereiakes DJ, Mick MJ, Navetta FI, Smith JE, Worley SJ. Multicenter, randomized, double-blind, placebo-controlled trial of the platelet integrin glycoprotein IIb/IIIa blocker integrelin in elective coronary intervention. Circulation 1995; 91: 2151-7.
    CrossrefPubMedGoogle Scholar
  • 21 The 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: 605-13.
    CrossrefPubMedGoogle Scholar
  • 22 The EPILOG Investigators. Platelet glycoprotein IIb/IIIa receptor blockade and low-dose heparin during percutaneous coronary revascularization. N Engl J Med 1997; 336: 1689-96.
    CrossrefPubMedGoogle Scholar
  • 23 The Organization to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. J Am Coll Cardiol 2001; 37: 475-84.
    CrossrefPubMedGoogle Scholar
  • 24 Van Es RF, Jonker JCJ, Verheugt FWA, Deckers JW, Grobbee DE. Aspirin, coumadin or both after acute coronary syndromes: results of the ASPECT-2 trial. Lancet 2002; 360: 109-13.
    CrossrefPubMedGoogle Scholar
  • 25 Weber A-A, Schrör K. The significance of platelet-derived growth factors for proliferation of vascular smooth muscle cells. Platelets 1999; 10: 77-96.
    CrossrefPubMedGoogle Scholar