Once- versus twice-daily direct oral anticoagulants in non-valvular atrial fibrillation

ABSTRACT

Introduction: Direct oral anticoagulants (DOACs) have emerged as alternatives to vitamin K antagonists for the prevention of stroke in patients with non-valvular atrial fibrillation (NVAF). Four DOACs: dabigatran, rivaroxaban, apixaban and edoxaban, are currently available. In the absence of head-to-head clinical comparisons of DOACs, dosing regimen may influence drug choice.

Areas covered: Edoxaban and rivaroxaban are administered once daily, dabigatran and apixaban twice daily. The selection of these dosage regimens is largely based on studies for the prevention or treatment of venous thromboembolism or acute coronary syndrome. Edoxaban is the only DOAC in which once and twice-daily regimens were compared in patients with NVAF; bleeding rates were higher in the twice-daily groups. Once-daily versus twice-daily regimens have a number of practical implications. Missing a once-daily dose would have a greater impact on anticoagulation. Some real world and retrospective studies found that a once-daily dosing regimen leads to better adherence and persistence to therapy, an important consideration for maintaining optimum anticoagulation. However, other studies have not found increased adherence among once daily regimens.

Expert opinion: Prescription of DOACs should be tailored to the individual patient and dosing regimen is only one of the variables that should be taken into account.

KEYWORDS:

• Non-valvular atrial fibrillation
• stroke prevention
• dosing regimen
• adherence
• persistence

Article highlights

• Studies on edoxaban suggest that bleeding rates might be correlated with C_min

• Varying distribution to the third compartment may influence trough levels of the DOACs.

• Missing a once-daily dose would have a greater impact on anticoagulation status than missing a twice-daily dose.

• While several studies suggest improved adherence with a once-daily dosage, results are inconsistent. A revised definition of adherence should help inform the design of future studies.

• Dosing regimen is one of only a number of factors that should be considered to tailor DOAC therapy to the individual patient

This box summarizes key points contained in the article.

Acknowledgments

The authors are grateful to the technical editing support provided by Katrina Mountfort and Bettina Vine of Medical Media Communications (Scientific) Ltd.

Declaration of interest

W Ageno has received research grants from Bayer and is on the Advisory Boards for Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Bristol-Myers Squibb and Pfizer. A Rubboli has received lecture fees from and/or consulted for Bayer, Boehringer Ingelheim, Daiichi-Sankyo and Pfizer Bristol Meyers Squibb. Medical writing assistance, provided by Katrina Mountfort and Bettina Vine of Medical Media Communications (Scientific) Ltd., was utilized in the production of this manuscript and funded by Daiichi-Sankyo. 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 funded by Daiichi-Sankyo.