Potent P2Y12 receptor inhibitors in patients with acute coronary syndrome

Summary

Blood platelets are highly activated in the setting of an acute coronary syndrome (ACS). This fact mandates the need for potent platelet inhibition in ACS patients and especially in patients undergoing a percutaneous coronary intervention (PCI). The 2^nd generation thienopyridine clopidogrel has been the standard of treatment in the past. Due to its pharmacological properties including a delayed onset of action, a large response variability and an insufficient antiplatelet action in some patients (low responsiveness or high on-treatment platelet reactivity), there was a need to develop, to study and to introduce more potent agents with a fast, reliable and potent antiplatelet action. With the 3^rd generation thienopyridine prasugrel and with ticagrelor two potent agents for antiplatelet treatment of ACS patients are available now. Both drugs have demonstrated their superiority compared to clopidogrel in terms of thrombotic risk reduction in large-scale randomized trials. However, for these agents and in line with the expectations towards a more potent anti platelet treatment regimen, a higher risk for bleeding was observed for prasugrel and ticagrelor. Further on, the new anti platelet agents have their own and characteristic contraindications and numerous issues to be considered in clinical practice.

This review aims to provide an overview on the state of the art P2Y12 receptor directed inhibition in ACS patients with a focus on patients undergoing a coronary stenting procedure.

Zusammenfassung

Im akuten Koronarsyndrom (ACS) zeigt sich eine ausgeprägte Aktivierung der Thrombozyten. Dieser Umstand erfordert die hochpotente medikamentöse Hemmung der Blutplättchen, ganz speziell bei Patienten, die einer perkutanen Koronarintervention zugeführt werden. Als Thienopyridin der zweiten Generation war Clopidogrel bisher die Standardtherapie für ACS-Patienten. Pharmakologisch betrachtet ist Clopidogrel, ein Antagonist des P2Y12 ADP-Rezeptors, jedoch durch einen verzögerten Wirkungseintritt, durch eine hohe Wirkungsvariabilität und durch eine nicht ausreichende antithrombozytäre Wirkung bei einigen Patienten charakterisiert. Daher war es notwendig, neue ADPRezeptorantagonisten zu entwickeln, zu testen und schließlich in die klinische Routine einzuführen, die sich durch schnell einsetzende, zuverlässige und potente antithrombozytäre Wirkung auszeichnen. Mittlerweile stehen mit dem Thienopyridin der dritten Generation Prasugrel und mit Ticagrelor zwei neue und potente ADP-Rezeptorantagonisten für die Therapie von ACS-Patienten zur Verfügung. Beide Medikamente haben ihre Überlegenheit im Vergleich zu Clopidogrel in Bezug auf die Reduktion von thrombotischen Ereignissen in großen randomisierten Studien unter Beweis gestellt. Jedoch zeigte sich passend zu den zu erwarteten Auswirkungen der hochpotenten antithrombozytären Therapie ein höheres Blutungsrisiko für Prasugrel und Ticagrelor. Ferner gibt es viele Details, die im klinischen Alltag bei Verwendung dieser neuen Substanzen zu berücksichtigen sind. Diese Übersicht soll die aktuelle P2Y12- Rezeptor-ausgerichtete Hemmung der Thrombo zyten bei ACS und speziell bei Patienten, die einer koronaren Stentimplantation zugeführt werden, zusammenfassend darstellen.

Keywords

Prasugrel - ticagrelor - clopidogrel - acute coronary syndrome

Schlüsselwörter

Prasugrel - Ticagrelor - Clopidogrel - akutes Koronar syndrom

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