Plättchenhemmung als Therapieprinzip der Primär- und Sekundärprophylaxe bei koronarer Herzkrankheit

Einleitung

Die koronare Herzerkrankung (KHK) ist die Manifestation der Atherosklerose an den Herzkranzarterien. In den Frühstadien der Erkrankung sind in der Regel keine klinischen Symptome vorhanden, obwohl die endotheliale Funktion bereits gestört und Lipide in der Gefäßwand eingelagert sind. Bei Plaquerupturen kommt es durch rasche Aktivierung von Thrombozyten zu akuten Ischämiesyndromen. Hier ist der Hauptansatzpunkt der Thrombozytenaggregationshemmer.

Nachdem ASS seit langem den Therapiestandard darstellt, haben Thienopyridine und Glykoprotein-IIb/IIIa-Rezeptorantagonisten in den letzten Jahren bei bestimmten Indikationen zunehmend an Bedeutung gewonnen. Wegen der neuen Definition des akuten Koronarsyndroms und wegen der Ergebnisse neuerer, sehr großer Therapiestudien haben alle großen kardiologischen Gesellschaften ihre Leitlinien aktualisiert. Im Folgenden soll der Stellenwert der Thrombozytenaggregationshemmung bei der Therapie von verschiedenen Manifestationen der KHK aufgezeigt werden.

Literatur

• 1 Carlo Patrono C, Coller B, Dalen J E, FitzGerald G A. et al . Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects.  CHEST. 2001;  119 39S-63S
• 2 Kallmann R, Nieuwenhuis H K, de Groot P G. et al . Effects of low doses of aspirin, 10 mg and 30 mg daily, on bleeding time, thromboxane production and 6-Keto-PGF1a excretion in healthy subjects.  Thromb Res. 1987;  45 355-361
• 3 Antiplatelet Trialists’ Collaboration . Collaborative overview of randomised trials of antiplatelet therapy I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.  BMJ. 1994;  308 81-106
• 4 Valles J, Santos M T, Aznar J. et al . Erythrocyte promotion of platelet reactivity decreases the effectiveness of aspirin as an antithrombotic therapeutic modality: The effect of low-dose aspirin is less than optimal in patients with vascular disease due to prothrombotic effects of erythrocytes on platelet reactivity.  Circulation. 1998;  97 350-355
• 5 Ridker P M, Cushman M. Stampfer MJ, et al. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.  N Engl J Med. 1997;  336 973-979
• 6 Jarvis B, Simpson K. Clopidogrel - a review of its use in the prevention of atherothrombosis.  Drugs. 2000;  60 347-377
• 7 McTavish D, Faulds D, Goa K L. Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders.  Drugs. 1990;  40 238-259
• 8 Caplain H, D’Honneur G, Cariou R. Lack of interaction of aspirin (1000 mg) with chronic clopidogrel in volunteers.  Haemostasis. 1996;  26 (Suppl 3) abstract no 557
• 9 Moshfegh K, Redondo M, Julmy F. et al . Antiplatelet effects of clopidogrel compared with aspirin after myocardial infarction.  J Am Coll Cardiol. 2000;  36 699-705
• 10 Auer J, Berent R, Laßnig E. et al . Thrombozytäre Glykoprotein-IIb/IIIa-Rezeptor-Blocker in der Behandlung der koronaren Herzkrankheit.  Herz. 2003;  28 393-403
• 11 Sanmuganathan P S, Ghahramani P, Jackson P R. et al . Aspirin for primary prevention of coronary heart disease: safety and absolute benefit related to coronary risk derived from meta-analysis of randomised trials.  Heart. 2001;  85 265-271
• 12 Harrington R A, Becker R C, Ezekowitz M. et al . Antithrombotic therapy for coronary artery disease. The seventh ACCP Conference on antithrombotic and thrombolytic therapy.  Chest. 2004;  126 513S-548S
• 13 Juul-Möller S, Edvardsson N, Jahmatz B. et al . Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. Swedish angina pectoris aspirin trial (SAPAT).  Lancet. 1992;  340 1421-1425
• 14 Ridker P M, Manson J E, Gaziano M. et al . Low-dose aspirin therapy for chronic stable angina: a randomised, placebo-controlled clinical trial.  Ann Intern Med. 1991;  114 835-839
• 15 Antiplatelet Trialists’ Collaboration . Collaborative overview of randomized trials of antiplatelet therapy: I. Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.  BMJ. 1994;  308 81-106
• 16 Dietz R, Rauch B. Leitlinie zur Diagnose und Behandlung der chronischen koronaren Herzerkrankung der Deutschen Gesellschaft für Kardiologie - Herz- und Kreislaufforschung (DGK).  Z Kardiol. 2003;  92 501-521
• 17 CAPRIE . A randomized, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events.  Lancet. 1996;  348 1329-1339
• 18 Patrono C, Bachmann F, Baigent C, Bode C, De Caterina R, Charbonnier B, Fitzgerald D. et al . European Society of Cardiology. Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology.  Eur Heart J. 2004;  25 (2) 166-181
• 19 Antithrombotic Trial Collaboration . Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.  BMJ. 2002;  324 71-86
• 20 Hamm C W. Leitlinien: Akutes Koronarsyndrom (ACS) Teil 1: ACS ohne persistierende ST-Hebung.  Z Kardiol. 2004;  93 72-90
• 21 The Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators . 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
• 22 ISIS-2 Collaborative Group . Randomised trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction.  Lancet. 1988;  2 349-360
• 23 Sabatine M S, Cannon C P, Gibson C M. et al . Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation.  N Engl J Med. 2005;  352 1179-1189
• 24 Doson C, Christopher L, Babor E-M. Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction. Letter to the Editor.  N Engl J Med. 2005;  352 2647-2648
• 25 Hamm C W. Leitlinien: Akutes Koronarsyndrom (ACS) Teil 2: ACS mit persistierender ST-Hebung.  Z Kardiol. 2004;  93 324-341
• 26 The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology . Guidelines for Percutaneous Coronary Interventions.  European Heart Journal. 2005;  26 804-807
• 27 Urban P, Macaya C, Rupprecht H J. et al . Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary stent implantation in high risk patients: The multicenter aspirin and ticlopidine trial after intracoronary stenting (MATTIS).  Circulation. 1998;  98 2126-2132
• 28 Bertrand M E, Rupprecht H, Urban P. et al . Clopidogrel aspirin stent international cooperative study. CLASSICS.  Circulation. 2000;  102 624-629
• 29 Silber S, Albertsson P, Aviles F F, Camici P G, Colombo A, Hamm C, Jorgensen E. et al . Task Force Members. Guidelines for percutaneous coronary interventions: the task force for percutaneous coronary interventions of the European society of cardiology.  Eur Heart J. 2005;  26 (8) 804-847
• 30 Levy M. Aspirin use in patients with major upper gastrointestinal bleeding and peptic-ulcer disease.  N Engl J Med. 1974;  290 1158-1162
• 31 Derry S, Loke Y K. Risk of gastrointestinal hemorrhage with long term use of aspirin: Meta-analysis.  Br Med J. 2000;  321 1183-1187
• 32 He J, Whelton P K, Vu B. et al . Aspirin and risk of hemorrhagic stroke: A meta-analysis of randomised controlled trials.  JAMA. 1998;  280 1930-1935
• 33 Hankey G J, Sudlow C LM, Dunbabin D W. Thienopyridines or aspirin to prevent stroke and other serious vascular events in patients at high risk of vascular disease? A systematic review of the evidence from randomized trials.  Stroke. 2000;  31 1779-1784
• 34 Bennett C L, Connors J M, Carwile J M. et al . Thrombotic thrombocytopenic purpura associated with clopidogrel.  N Engl J Med. 2000;  342 1773-1777
• 35 The EPIC Investigators . Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty.  N Engl J Med. 1994;  330 956-961
• 36 Patrono C. Aspirin resistance: definition, mechanisms and clinical read-outs.  J Thromb Haemost. 2003;  1 1710-1713
• 37 Geiger J, Teichmann L, Grossmann R. et al . Monitoring of Clopidogrel Action: Comparison of Methods.  Clinical Chemistry. 2005;  51(6) 957-965
• 38 Grotemeyer K H, Scharafinski H W, Husstedt I W. Two year follow-up of aspirin responder and aspirin non responder. A pilot study including 180 poststroke patients.  Thromb Res. 1993;  71 397-403
• 39 Gum P A, Kottke-Marchant K, Welsh P A, White J, Topol E J. A prospective, blinded determination of the natural history of aspirin resistance among stable patients with cardiovascular disease.  J Am Coll Cardiol. 2003;  41 961-965
• 40 Barragan B, Bouvier J-L, Roquebert P-O, Macaluso G, Commeau P, Comet B, Lafont A, Camoin L, Walter U, Eigenthaler M. Resistance to Thienopyridines: Clinical Detection of Coronary Stent Thrombosis by Monitoring of Vasodilator-Stimulated Phosphoprotein Phosphorylation.  Cathet Cardiovasc Intervent. 2003;  59 295-302