Approaches to de-escalation of antiplatelet treatment in stabilized post-myocardial infarction patients with high ischemic risk

ABSTRACT

Introduction

In patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI), dual antiplatelet therapy (DAPT) with a potent P2Y₁₂ inhibitor is normally recommended for 12 months. However, the greatest anti-ischemic benefit of DAPT occurs early, while most excess bleeding events occur during chronic treatment. De-escalation of DAPT is an emerging treatment strategy for ACS patients.

Areas covered

This review critically evaluates the evidence for de-escalation based on clinical judgment (i.e. unguided) or guided by either platelet function testing or CYP2C19 genotyping. Ongoing trials and research directions are also discussed.

Expert opinion

De-escalation of antiplatelet therapy represents a viable therapeutic alternative to standard DAPT for patients after an ACS, aimed at providing a good balance between the risks of thrombosis and bleeding. It is not clear if this approach is better with or without guidance by platelet function testing or genotyping. Also, the benefit versus short DAPT is uncertain. Current guidelines support the de-escalation of DAPT for selected patients who are unsuitable for potent platelet inhibition, a cohort of patients that was not specifically represented in landmark trials of de-escalation. More studies are needed to define the optimal candidates for this strategy.

KEYWORDS:

• De-escalation
• antiplatelet therapy
• acute coronary syndromes

Article highlights

• De-escalation of DAPT is an emerging treatment strategy for patients with ACS.

• In regulatory trials, the greatest benefit of prasugrel and ticagrelor was observed early after the acute event, while the risk of bleeding was evenly distributed over time. As such, the net benefit of potent P2Y₁₂ inhibition may be more pronounced in the initial versus the late period.

• Current European guidelines support de-escalation of DAPT as an alternative to standard DAPT in patients unsuitable for long-term potent platelet inhibition.

• Several trials of de-escalation are ongoing.

Declaration of Interest

D Angiolillo has received consulting fees or honoraria from Abbott, Amgen, Aralez, AstraZeneca, Bayer, Biosensors, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, Daiichi-Sankyo, 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. Dr Angiolillo’s institution has received research grants from 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. D Capodanno reports advisory board or speaker’s honoraria from Amgen, Chiesi, Daiichi Sankyo, Sanofi, Terumo.

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.