Dilemma zwischen Magenschutz und Kardioprotektion

 

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Zusammenfassung

Eine Dauermedikation mit niedrig dosierter Acetylsalicylsäure (ASS) erhöht das Risiko einer Blutung aus dem oberen Gastrointestinaltrakt um das 2 - bis  4-fache. Die zusätzliche Einnahme von Clopidogrel erhöht das Risiko einer oberen gastrointestinalen Blutung weiter um das 7 - bis 8-fache. Aufgrund der möglichen Interaktion der Protonenpumpenhemmer (PPI) mit Clopidogrel, die sich auf eine verminderte Wirksamkeit von Clopidogrel auf die Plättchenaggregationshemmung auswirkt, wurde vor der gleichzeitigen Verschreibung dieser beiden Substanzen von europäischen und amerikanischen Gesundheitsbehörden gewarnt. In der vorliegenden Arbeit haben wir eine selektive Literatursuche zur Indikation der PPI-Medikation bei Patienten unter mono- oder dualer Plättchenaggregationshemmung durchgeführt und die publizierten klinischen Studien hinsichtlich der möglichen Interaktion zwischen Clopidogrel und PPI kritisch geprüft.

In ex vivo-Analysen der Thrombozytenfunktion führt Omeprazol zum Verlust der plättchenaggregationshemmenden Wirkung von Clopidogrel. Dies ist nicht der Fall, wenn andere PPI gleichzeitig mit Clopidogrel gegeben werden. Die aktuelle klinische Datenlage ist derzeit nicht hinreichend, daraus die allgemeine Aussage abzuleiten, dass die gleichzeitige Einnahme von PPI und Clopidogrel zu einem klinisch relevanten Verlust der plättchenhemmenden Wirkung von Clopidogrel führt. Bei Indikation zur gleichzeitigen Gabe von Clopidogrel und PPI, sollte die Einnahme des PPI morgens und Clopidogrel abends erfolgen. Die kurze Halbwertszeit beider Präparate begründet den pharmakologischen Hintergrund für diesen Ansatz.

Abstract

Long-term low-dose aspirin intake leads to a 2 – 4-fold risk of risk for upper gastrointestinal bleeding. The additional intake of clopidogrel further increases the risk of upper GI bleeding (OR 7.4). Because of the potential interaction between proton pump inhibitors (PPI) and clopidogrel that compromises the efficacy of clopidogrel on platelet aggregation, there has been a warning in the product information by health authorities in the US and in Europe who discourage the concomitant use of PPI and clopidogrel. In the present study we performed a selected review of the published literature on the indications for gastric protection with PPI in patients on mono- or dual antiplatelet therapy focussing on the possible interaction between clopidogrel and PPI.

In ex vivo analyses of platelet function, a reduced efficacy of clopidogrel was observed in patients on comedication with omeprazole. This was not the case with the comedication of other PPIs. To date, clear evidence is missing to state that comedication with PPI reduces the efficacy of clopidogrel in vivo. If both Clopidogrel and PPI need to be prescribed, a split dosage regimen of PPI in the morning and clopidogrel in the evening can be recommended. The short half-life of both medications explains the rationale of this recommendation.

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Prof. Dr. med. Peter Malfertheiner

Klinik für Gastroenterologie, Hepatologie und Infektiologie
Otto-von-Guericke-Universität Magdeburg

Leipziger Str. 44

39120 Magdeburg

Phone: 0391/6713100

Fax: 0391/6713105

Email: Peter.Malfertheiner@med.ovgu.de