Pharmacodynamic and clinical efficacy of reduced ticagrelor maintenance doses in patients with coronary artery disease

Abstract

Objective

An increasing body of data indicates that a reduction of ticagrelor maintenance dose (MD) in stabilized patients might improve ticagrelor’s safety profile and adherence to the treatment. The aim of this review was to discuss the rationale and summarize the current pharmacodynamic and clinical outcomes-based evidence from reduced MD of ticagrelor in patients with coronary artery disease (CAD).

Methods

A narrative systematic review based on a literature search using the PubMed database from its inception through to June 2020. A search strategy included a combination of relevant search terms regarding ticagrelor reduced MD. The pre-determined inclusion criteria were: (1) randomized or observational trials; (2) presentation of clinical or pharmacodynamic results; (3) evaluation of any ticagrelor MD below 90 mg BID in patients with CAD.

Results

Studies evaluating the following ticagrelor reduced MD have been identified: 90 mg QD, 60 mg BID, 60 mg QD, 45 mg BID, 22.5 mg BID. Majority of trials assessing doses <60 mg BID were performed in Asian patients only. Antiplatelet effect of ticagrelor in CAD decreases with the dose, however even reduced MDs provide sufficient platelet inhibition, which is greater than in clopidogrel-treated patients. De-escalation of ticagrelor dose shows a propensity towards a reduced rate of bleeding and non-bleeding adverse events.

Conclusions

Ticagrelor doses below 90 mg BID generally show an acceptable profile of platelet inhibition. The number of studies reporting clinical outcomes in CAD patients receiving reduced MD of ticagrelor are limited, however available results indicate that in a stable setting this strategy offers improved safety with preserved efficacy in the prevention of thrombotic events.

Keywords:

• Acute coronary syndrome
• coronary artery disease
• de-escalation
• reduced maintenance dose
• ticagrelor

Transparency

Declaration of funding

This manuscript was not funded.

Declaration of financial/other relationships

PA has received a lecture fee from AstraZeneca, JK has received lecture and consultancy fees from AstraZeneca. 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. A reviewer on this manuscript has disclosed being an investigator and steering committee member for the PEGASUS trial. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

PA, MO, EPN and JK contributed to conception and design of the review, PA and MO conducted the literature search and assembled data, JK resolved discrepancies regarding review data, PA wrote the draft of the manuscript with help of MO, all authors reviewed and approved the final content of this manuscript.

Acknowledgements

None reported.