Antithrombotische Therapie bei akutem Koronarsyndrom

Zusammenfassung

In Deutschland werden jährlich etwa 350 000–400 000 Patienten mit akutem Koronarsyndrom ohne persistierende ST-Streckenhebung (instabile Angina pectoris und Nicht-ST-Hebungsinfarkt) behandelt. Gemeinsames pathophysiologisches Substrat beider klinisch akut lebensbedrohlichen Manifestationsformen der koronaren Herzerkrankung ist in aller Regel die Erosion oder Ruptur der atherosklerotischen Plaque, die zur Thromboyztenaktivierung und Thrombusbildung führt. Die antithrombotische Therapie ist ein zentraler Bestandteil der Therapie der akuten Koronarsyndrome. In den vergangenen Jahren ist das Gebiet der plättchenhemmenden und antithrombotischen Therapie um einige neue Wirkstoffe bereichert worden, die die Prognose von Patienten mit akutem Koronarsyndrom verbessert haben. Diese Arbeit stellt die aktuellen Empfehlungen zur kombinierten gerinnungshemmenden Therapie bei akutem Koronarsyndrom ohne ST-Streckenhebung (instabile Angina pectoris und NSTEMI) zusammenfassend dar.

Summary

Recent advances in the diagnosis and the treatment of acute coronary syndromes (ACS) have led to a substantial reduction of major coronary events, to an improvement in patient outcome, and to the definition of new guidelines. Current strategies for the treatment of patients with non-STelevation ACS recommend a combined antithrombotic therapy (including acetyl salicylic acid, clopidogrel, low-molecular weight or unfractionated heparins and, eventually glycoprotein IIb/IIIa receptor antagonists). This combined antithrombotic therapy allows to increase the benefit of an early invasive strategy including coronary angiogram with stent percutaneous coronary angioplasty. The purpose of this review is to discuss and highlight the actual recommendations for the appropriate use of antithrombotic strategies for ACS patients.

Schlüsselwörter

Antithrombotika - akutes Koronarsyndrom - Plättchenhemmung

Keywords

Acute coronary syndromes - antithrombotic therapy

• Literatur

• 1 Alpert JS, Thygesen K, Antman E. et al. 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 2000; 36: 959-69.
• 2 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: E1-211.
• 3 Bertrand ME, Simoons ML, Fox KA. et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2002; 23: 1809-40.
• 4 Bittl JA, Chaitman BR, Feit F. et al. Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina: Final report reanalysis of the Bivalirudin Angioplasty Study. Am Heart J 2001; 142: 952-9.
• 5 Blazing MA, de Lemos JA, White HD. et al. Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial. JAMA 2004; 292: 55-64.
• 6 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: 189-98.
• 7 Braunwald E, Antman EM, Beasley JW. et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: executive summary and recommendations. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (committee on the management of patients with unstable angina). Circulation 2000; 102: 1193-209.
• 8 Cannon CP, Weintraub WS, Demopoulos LA. et al. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001; 344: 1879-87.
• 9 Cohen M, Demers C, Gurfinkel EP. et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997; 337: 447-52.
• 10 Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324: 71-86.
• 11 Coller BS, Peerschke EI, Scudder LE. et al. A murine monoclonal antibody that completely blocks the binding of fibrinogen to platelets produces a thrombasthenic-like state in normal platelets and binds to glycoproteins IIb and/or IIIa. J Clin Invest 1983; 72: 325-38.
• 12 Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). Eur Heart J 1999; 20: 1553-62.
• 13 Eikelboom JW, Hirsh J, Weitz JI. et al. Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation 2002; 105: 1650-5.
• 14 Ferguson JJ, Califf RM, Antman EM. et al. 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 2004; 292: 45-54.
• 15 Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: 311-22.
• 16 Fox KA, Poole-Wilson PA, Henderson RA. et al. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet 2002; 360: 743-51.
• 17 FRagmin and Fast Revascularisation during In-Stability in Coronary artery disease Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999; 354: 708-15.
• 18 Hamm CW, Braunwald E. A classification of unstable angina revisited. Circulation 2000; 102: 118-22.
• 19 Hamm CW. Guidelines: Acute coronary syndrome (ACS). II: Acute coronary syndrome with ST-elevation. Z Kardiol 2004; 93: 324-41.
• 20 Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79: 1-17.
• 21 Klein W, Buchwald A, Hillis SE. et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC). Circulation 1997; 96: 61-8.
• 22 Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995; 332: 1553-9.
• 23 Lincoff AM, Bittl JA, Harrington RA. et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003; 289: 853-63.
• 24 Madan M, Tcheng JE. Update on Abciximab Readministration During Percutaneous Coronary Interventions. Curr Interv Cardiol Rep 2000; 2: 244-9.
• 25 Mehta SR, Yusuf S, Peters RJ. et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001; 358: 527-33.
• 26 Moons AH, Levi M, Peters RJ. Tissue factor and coronary artery disease. Cardiovasc Res 2002; 53: 313-25.
• 27 Naghavi M, Libby P, Falk E. et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation 2003; 108: 1664-72.
• 28 Oler A, Whooley MA, Oler J. et al. 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.
• 29 Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Effects of recombinant hirudin (lepirudin) compared with heparin on death, myocardial infarction, refractory angina, and revascularisation procedures in patients with acute myocardial ischaemia without ST elevation: a randomised trial. Lancet 1999; 353: 429-38.
• 30 Petersen JL, Mahaffey KW, Hasselblad V. et al. Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview. JAMA 2004; 292: 89-96.
• 31 Schror K. Clinical pharmacology of the adenosine diphosphate (ADP) receptor antagonist, clopidogrel. Vasc Med 1998; 3: 247-51.
• 32 Shah PB, Ahmed WH, Ganz P. et al. Bivalirudin compared with heparin during coronary angioplasty for thrombus-containing lesions. J Am Coll Cardiol 1997; 30: 1264-9.
• 33 Simoons ML, Bobbink IW, Boland J. et al. A dosefinding study of fondaparinux in patients with non-ST-segment elevation acute coronary syndromes: the Pentasaccharide in Unstable Angina (PENTUA) Study. J Am Coll Cardiol 2004; 43: 2183-90.
• 34 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: 775-82.
• 35 Viles-Gonzalez JF, Fuster V, Badimon JJ. Atherothrombosis: a widespread disease with unpredictable and life-threatening consequences. Eur Heart J 2004; 25: 1197-207.
• 36 Wallentin LC. Aspirin (75 mg/day) after an episode of unstable coronary artery disease: long-term effects on the risk for myocardial infarction, occurrence of severe angina and the need for revascularization. Research Group on Instability in Coronary Artery Disease in Southeast Sweden. J Am Coll Cardiol 1991; 18: 1587-93.
• 37 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.