P2Y12 inhibitors for the treatment of acute coronary syndrome patients undergoing percutaneous coronary intervention: current understanding and outcomes

ABSTRACT

Introduction: Inhibition of P2Y₁₂ platelet receptors consists a crucial target of pharmacologic treatment in acute coronary syndrome patients. Several controversial issues however still remain and these are analyzed.

Areas covered: The significance of early and strong platelet inhibition in the early phase of STEMI and the role of pretreatment are discussed. Concerns regarding morphine administration are raised. The role of crushing integral tablets to expedite the onset of action of oral P2Y₁₂ inhibitors is emphasized. New data on the intravenous cangrelor are reported. Antiplatelet therapies as adjunct to thrombolysis, as well as the role of de-escalation antiplatelet therapy are analyzed.

Expert opinion: Pharmacodynamic studies convincingly demonstrate a gap in the onset of antiplatelet action in STEMI cases, even when prasugrel or ticagrelor loading dose is used. The clinical benefit, however, of the early platelet inhibition and pretreatment is not entirely clear. Morphine delays the onset of action of oral agents, while this is expedited by crushing the integral tablets. Cangrelor devoids of these deficiencies by achieving fast and strong platelet inhibition in all clinical scenarios. Concomitant administration of novel antiplatelet agents with thrombolysis and de-escalation of antiplatelet treatment necessitate further study to reach definite conclusion.

KEYWORDS:

• Antiplatelet therapy
• acute coronary syndrome
• percutaneous coronary intervention
• bleeding
• stent thrombosis

Article highlights

• Treatment of acute coronary syndrome patients with potent P2Y₁₂ inhibitors is considered as standard therapy. Prasugrel and ticagrelor act faster and more consistently than clopidogrel and in the absence of contraindications, have replaced it in most cases. However, pharmacodynamic studies convincingly demonstrate a gap in their onset of their action in STEMI cases.

• Although pretreatment in STEMI is suggested, the clinical benefit of early platelet inhibition is not entirely clear.

• Morphine delays oral P2Y₁₂ inhibitors absorption and delay the onset of action of oral agents. Unless considered truly necessary, morphine administration is not suggested.

• Crushing the integral tablets of antiplatelet agents expedites the onset of their action. This modality of administration is also used in comatose, intubated or unable to swallow patients.

• Cangrelor is an intravenous P2Y₁₂ inhibitor with fast and strong platelet inhibition in all clinical scenarios. Cangrelor’s use in STEMI is increasing in real life practice, although its clinical superiority over potent oral agents is unexplored.

• Concomitant administration of novel antiplatelet agents with thrombolysis is discouraged, although switching from clopidogrel to ticagrelor approximately 12 hours post thrombolysis appears to be safe.

• De-escalation of antiplatelet treatment may be considered in several cases (i.e. bleeding, side effects, cost issues), guided by platelet function testing. Routine use is not suggested due to lack of data.

Declaration of interest

D Alexopoulos is on the tecturing/Advisory board fees by Astrazeneka, Bayer, Boehringer Ingelheim, Pfizer, AMGEN, Chiesi Hellas and Medtronicfo. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.