Was bringen die neuen Plättchenfunktionshemmer beim akuten Koronarsyndrom?

Abstract

Ticagrelor and prasugrel are two novel promising antiplatelet compounds inhibiting the P2Y12 receptor with different pharmacokinetic characteristics compared to clopidogrel.

Clopidogrel owes a high response variability due to its complex pharmacokinetics and the vulnerability in genes involved in metabolism and drug interactions, especially polymorphisms of the CYP2C19 pathway. Comorbidities like diabetes, acute coronary syndrome, left ventricular dysfunction, or renal insufficiency influence the platelet activity and response.

Prasugrel and Ticagrelor show a simpler metabolism, leading to greater bioavailability and seem to be less affected by genetic factors. However, drug interactions were described. Both achieve their antiplatelet effect faster and to a greater extent than clopidogrel. All these differences explain the efficacy and safety profile observed in clinical trials. Clopidogrel is still the best standard of care. However, the pharmacokinetic advantages of prasugrel and ticagrelor allow clinicians to center patient management by selecting the best drug for each patient individually.

Kernaussagen

• Bei KHK mit stabiler Angina pectoris und elektiver Koronarintervention oder konservativem Vorgehen sind nur ASS und Clopidogrel – allein oder in Kombination – zur plättchenhemmenden Therapie zugelassen.

• Clopidogrel-„Low-Responder“ sind Risikopatienten für ein erneutes kardiovaskuläres Ereignis nach Koronarintervention.

• Eine individuelle Anpassung der Clopidogreldosis verbessert zwar den allgemeinen Therapieerfolg, dennoch profitieren nicht alle Patienten.

• Die antithrombotische Therapie des ACS sollte individuell angepasst werden in Abhängigkeit von klinischen Gesichtspunkten wie Begleiterkrankungen und Blutungsrisiko sowie nach dem Ansprechen auf die antiaggregatorische Therapie. Eine Kombination mit ASS ist dabei die Therapie der Wahl. Die empfohleneTherapiedauer nach ACS beträgt 12 Monate.

• Von der Behandlung mit Prasugrel profitieren Diabetiker mit ACS, STEMI-Patienten und Patienten mit Stentthrombose unter Clopidogrel nach Intervention am meisten. Erhöhtes Blutungsrisiko, zerebraler Insult oder transitorisch-ischämische Attacke sowie ein Alter über 75 Jahre und ein Körpergewicht unter 60 kg stellen Kontraindikationen dar.

• Unter Ticagrelor wurde sowohl eine geringere Gesamtmortalität als auch eine geringere kardiovaskuläre Mortalität im Vergleich zu Clopidogrel beobachtet. Bezüglich einer Reduktion ischämischer Endpunkte ist Ticagrelor ebenso effektiv wie Prasugrel, mit vergleichbar erhöhter Blutungsrate. Hämorrhagischer Insult in der Anamnese stellt eine Kontraindikation dar. Problematisch ist auch die Notwendigkeit einer Zweimaldosierung von Ticagrelor in der Praxis.

• Bei konservativ therapiertem ACS ist derzeit nur eine duale Therapie mit ASS und Clopidogrel vorgesehen. In der Therapie von primär interventionell versorgtem STEMI und NSTEMI sind nach ESC-Leitlinien Prasugrel und Ticagrelor empfohlen und nur bei Kontraindikationen für die beiden Substanzen Clopidogrel.

• Prasugrel und Ticagrelor führen gleichermaßen zu einer rascheren Hemmung der Thrombozytenaggregation als Clopidogrel, die Variabilität der Wirkung ist deutlich geringer und der Effekt ausgeprägter. Bei beiden Substanzen zeigt sich jedoch ein vermehrtes Auftreten an schweren, nicht bypassassoziierten Blutungen.

• Clopidogrel ist klinisch weiterhin der am häufigsten eingesetzte P2Y12-Rezeptorantagonist. Clopidogrel findet weiterhin seine Anwendung bei interventionell behandelten Patienten mit stabiler kardiovaskulärer Erkrankung und ACS sowie bei medikamentös-konservativ behandelten Patienten mit ACS bzw. bei Kontraindikation für die neuen P2Y12-Rezeptorantagonisten.

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