Tackling the gap in platelet inhibition with oral antiplatelet agents in high-risk patients undergoing percutaneous coronary intervention

ABSTRACT

Introduction: Oral P2Y₁₂ inhibitors represent the mainstay therapy for the prevention of thrombotic complications in patients presenting with an acute coronary syndrome and/or undergoing percutaneous coronary intervention (PCI). However, the onset of antiplatelet action of the oral P2Y₁₂ inhibitors is affected by their need to be absorbed in the gastrointestinal (GI) tract before becoming systemically available.

Areas covered: Following oral intake of P2Y₁₂ inhibitors, the timeframe required for GI absorption leads to a window of inadequate antiplatelet protection during which patients are at increased thrombotic risk. The onset of action of the oral P2Y₁₂ inhibitors is even further delayed in high-risk patients, underscoring the need to define strategies to bridge the gap in platelet inhibitory effects following their intake.

Expert opinion: Multiple mechanisms may impair GI absorption leading to a delay in the onset of action of oral P2Y₁₂ inhibitors. Several strategies have been tested to overcome the gap in platelet inhibition in high-risk patients undergoing PCI. These include administration of crushed or chewed tablets to improve the dissolution rate and use of opioid receptor antagonists or metoclopramide to counteract impairment of gastric motility induced by opioids. However, intravenous antiplatelet therapies represent the most effective strategy to bridge such gap in platelet inhibition.

KEYWORDS:

• Oral P2Y₁₂ inhibitors
• pretreatment
• crushed
• chewed
• cangrelor
• glycoprotein IIb/IIIa inhibitors

Article highlights

• Due to the time required for gastrointestinal absorption, there is a delay between oral P2Y₁₂ inhibitors intake and time of reaching effective platelet inhibition.

• The onset of action of the oral P2Y₁₂ inhibitors is even further delayed in high-risk patients, such as those presenting an acute myocardial infarction.

• The gap in platelet inhibition with oral agents leads to a window of inadequate antiplatelet protection during which patients are at increased risk of thrombotic events.

• Early treatment, administration of crushed or chewed tablets, or the use of agents counteracting the opioids-related delay of absorption are among strategies to speed the onset of action of oral P2Y12-inhibitors.

• The more rapid and potent intravenous antiplatelet therapies represent the most effective strategy to bridge the gap in platelet inhibition after oral agents intake.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they are a speaker for Chiesi USA. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Declaration of interest

D Angiolillo declares that he has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, DaiichiSankyo, Eli Lilly, Haemonetics, Janssen, Merck, PhaseBio, PLx Pharma, Pfizer, Sanofi, and The Medicines Company and has received payments for participation in review activities from CeloNova and St Jude Medical. D.J.A. also declares that his institution has received research grants sfrom Amgen, AstraZeneca, Bayer, Biosensors, CeloNova, CSL Behring, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Idorsia, Janssen, Matsutani Chemical Industry Co., Merck, Novartis, Osprey Medical, Renal Guard Solutions, and the Scott R. MacKenzie Foundation. 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.

Additional information

Funding

This paper was not funded.