Zusammenfassung
Wesentlicher Bestandteil des medikamentösen Behandlungsprinzips beim akuten Koronarsyndrom (ACS) ist die Thrombozytenaggregationhemmung. Während der Einsatz von Acetylsalicylsäure etabliert ist, wird inzwischen durch die Leitlinien der amerikanischen, europäischen und deutschen Gesellschaften für Kardiologie die additive Gabe von Clopidogrel bei ACS ohne persistierende ST-Hebung empfohlen. Bei konservativem Therapiemanagement soll die möglichst frühe Gabe von 75 mg Clopidogrel für die Dauer von einem (Empfehlung IA) bis zu neun Monaten (IB) erfolgen. Bei geplanter PTCA wird zusätzlich vorab eine „loading dose“ von 300 mg Clopidogrel empfohlen.
Diese Empfehlungen beruhen hauptsächlich auf den Daten der CURE- und CREDO-Studie, die allerdings nicht alle Fragen beantworten. Die absolute Risikoreduktion durch Clopidogrel in diesen Studien betrug lediglich 2%. Dabei wurde nur die Inzidenz des kombinierten Endpunktes bestehend aus kardiovaskulärem Tod, Myokardinfarkt und Schlaganfall statistisch signifikant beeinflusst, wohingegen sich bei der Analyse der Endpunkte im Einzelnen kein Unterschied ergab. Auch die Empfehlung bezüglich der Dauer der Clopidogrelbehandlung beruht lediglich auf der mittleren Applikationszeit der beiden Studien. Aufgrund des erhöhten Blutungsrisiko unter Clopidogrel (schwere Blutungen ca. 1%) bleibt die Frage nach der Rationale für eine duale antiaggregatorischen Behandlung bei ACS damit nach wie vor nur teilweise beantwortet. Betrachtet man zudem die Kosten, die durch die Clopidogrelbehandlung entstehen, erscheint die Forderung nach weiteren Studien, die die Effektivität der dualen antiaggregatorischen Therapie weiter untermauern, gerechtfertigt. Bis dahin sind die auf den Leitlinien basierenden Behandlungsschemata unter besonderer Berücksichtigung des individuellen Risikos des Patienten anzuwenden.
Summary
An important part of the therapy management of acute coronary syndrome (ACS) consists of antiplatelet drugs. Whereas the administration of acetylsalicylic acid (ASA) is well established, the guidelines recommend the additive use of clopidogrel in patients with ACS without persisting ST-elevation. Clopidogrel should be added to ASA as soon as possible in patients with a non-invasive treatment strategy and continued for more than 1 month (class 1A) and up to 9 months (class 1B). In patients for whom a percutaneous coronary intervention (PCI) is planned, an additional loading-dose of 300 mg clopidogrel should be given on top of ASA (100 mg).
These recommendations are based on data recently published in the CURE and CREDO trials, which however should be critically discussed: In these trials, an absolute risk reduction of only 2% could be documented by additive use of clopidogrel. The combined endpoint of cardiovascular death, myocardial infarction and stroke is significantly reduced, but there was no improvement taken the individual endpoints alone. In additional, the data for duration of clopidogrel therapy were determined by taken the mean follow-up of these studies. The efficacy of the dual antiplatelet therapy should be discussed in the context of an increased frequency of major bleedings (in total 1%) and should be considered against a reasonable cost effective background.
An adequate therapy with clopidogrel in patients presenting ACS should be confirmed by further trials. Until more detailed data are available, the guideline recommendations should be implemented based on of patient’s individual risk.
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Elsässer, A., Nef, H., Möllmann, H. et al. Clopidogrel in acute coronary syndrome: when, how much, how long?. ZS Kardiologie 94, 377–382 (2005). https://doi.org/10.1007/s00392-005-0224-3
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DOI: https://doi.org/10.1007/s00392-005-0224-3