ABSTRACT
Introduction
Ticagrelor is an antiplatelet agent acting through direct and reversible competitive inhibition of the platelet P2Y12 receptor. While the clinical merits of ticagrelor in patients who experienced an acute coronary syndrome are widely accepted, its role in stable coronary artery disease is less established. Recently, large-scale trials of ticagrelor have been published in this setting, including a trial in patients with diabetes mellitus (DM).
Areas covered
This review aims to inform about recent findings on ticagrelor, by appraising the current body of evidence on its use in different clinical scenarios, particularly in DM, ranging from pharmacology to clinical outcomes and future directions.
Expert opinion
The results of the THEMIS trial, conducted in DM patients with stable coronary artery disease and no prior stroke or myocardial infarction, showed that although ticagrelor in addition to aspirin reduced the risk of ischemic events, this was associated with a parallel increase in bleeding complications. However, patients with history of percutaneous coronary intervention seemed to benefit more from adjunctive ticagrelor therapy. Careful bleeding and ischemic risk stratification remains crucial to define the best antithrombotic strategy for the individual patient.
Article highlights
Ticagrelor is a direct and reversible P2Y12 inhibitor with a rapid onset and offset of action.
Pharmacodynamic studies have demonstrated higher platelet inhibition with ticagrelor compared to clopidogrel.
A pivotal regulatory trial demonstrated a reduction in ischemic events, including cardiovascular mortality, in patients treated with ticagrelor (180 mg loading dose followed by 90 mg bid maintenance dose) compared to clopidogrel after an acute coronary syndrome (ACS). Although this occurred at the expense of increased bleeding, the benefits outweighed the risks.
Practice guidelines recommend an early initiation of ticagrelor in the ACS context.
In a study of patients with prior myocardial infarction (1-3 years prior) and cardiovascular risk factors, ticagrelor significantly reduced ischemic events compared to placebo at the expense of increased bleeding. The ticagrelor 60 mg bid regimen had the most favourable safety profile in this study and was accordingly approved for this purpose.
The benefits of ticagrelor in patients who experienced an ACS were consistent among patients with diabetes mellitus.
Ticagrelor monotherapy after a short period (3 months) of DAPT reduces bleeding compared with standard DAPT at 12 months.
In diabetes mellitus patients with stable coronary artery disease and no prior stroke or myocardial infarction, ticagrelor in addition to aspirin reduced the risk of ischemic events, but this was associated with a parallel increase in bleeding complications. The net benefit of this strategy is enhanced in patients with prior percutaneous coronary intervention.
Careful bleeding and ischemic risk stratification remains crucial to define the best antithrombotic strategy for the individual patient.
Declaration of interest
Dario Calderone has nothing to disclose. Davide Capodanno discloses the following relationships: Advisory Board: Bayer, Daiichi Sankyo. Lecture fees: AstraZeneca, Bayer, Daiichi Sankyo. Dominick J. Angiolillo declares that he 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. D.J.A. also declares that his 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.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.