Neuentwicklungen in der Thrombozytenaggregationshemmung – sinnvolle Alternativen für ASS/Clopidogrel-Non-Responder?
Tóm tắt
Thrombozytenaggregationshemmer (TAH) wie Aspirin und Clopidogrel spielen eine überragende Rolle bei der Prävention kardiovaskulärer Ereignisse bei Patienten mit koronarer Herzkrankheit nach einem akuten Koronarsyndrom oder nach Implantation von Koronarstents. Ein klinisches Problem dieser Substanzen stellt allerdings die „Non-Responder“-Rate von bis zu 30% dar, welche auf eine Vielzahl von klinischen, genetischen und zellulären Faktoren zurückzuführen ist. Deshalb wird nach neuen Substanzen – insbesondere nach Inhibitoren des P2Y12-Rezeptors – gefahndet, welche eine reversible Bindung an den Rezeptor, eine rasch einsetzende und möglichst starke und wenig streuende Wirkung ohne den Umweg einer hepatischen Metabolisierung (kein „Pro- Drug“) gewährleisten. Zu diesen neuen TAH zählen Cangrelor, AZD6140 und Prasugrel, drei neue P2Y12-Rezeptorantagonisten, deren bisher vorliegenden klinischen Ergebnisse dargestellt werden. Die Neuentwicklungen von TAH sind aber nicht abgeschlossen; als interessante weitere Targets werden Antikörper bzw. Aptamere gegen den Kollagenrezeptor GPVI bzw. den vWWRezeptor GP1b, Antagonisten gegen den Thromboxanrezeptor sowie Antagonisten der Proteaseaktivierten Rezeptoren (PAR) experimentell und klinisch geprüft.
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