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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Dr. med. Karin A. L. Müller
Medizinische Klinik III
Eberhard-Karls-Universität Tübingen
Otfried-Müller-Straße 10
72076 Tübingen
eMail: k.mueller@med.uni-tuebingen.de
