Non-vitamin K antagonist oral anticoagulants: considerations on once- vs. twice-daily regimens and their potential impact on medication adherence

Abstract

Suboptimal medication adherence is a widespread problem in ambulatory care of chronic diseases, with deviations in either direction from the prescribed dosing regimen. For the non-vitamin K antagonist oral anticoagulants (NOACs), such deviations occur and can lead to bleeding or clotting, as suboptimal adherence involves temporary periods of either overdosing or underdosing. In this expert review, we discuss: (a) the proper definition of adherence in terms of its three elements: initiation, implementation, and discontinuation; (b) how adherence is reliably and accurately measured and (c) successfully enhanced, to achieve and maintain safe and effective levels of NOAC-based anticoagulation. We also discuss the comparative effects of prescribing the same total daily dose, given either once-daily or as half-strength twice-daily doses. Because NOACs have plasma half-lives of ∼12 h, the twice-daily dosing regimen is less prone than the once-daily dosing regimen to hazardously high peaks or hazardously low troughs in anticoagulant concentrations and associated actions. As in other fields of oral drug treatment, the continuity of drug action is greater with twice-daily than with once-daily dosing, despite the fact that a few more doses are skipped with twice-daily than with once-daily dosing. This paradox is explained by the disproportionately greater impact on drug action of skipping a once-daily than a twice-daily dose. Integration of these principles into real-world medication management is the next step in the improvement of oral anticoagulation.

Coagulation Testing in Acute Ischemic Stroke Patients Taking Non–Vitamin K Antagonist Oral Anticoagulants

“…20 This has been of particular concern for NOACs with once-daily dosing regimens where a single missed dose may result in critically low concentrations. 21 Notably, results of coagulation tests in our study suggest that failure to take a NOAC immediately before the stroke may not be associated with a substantially increased stroke risk. Only 12% of patients with available specific coagulation tests had no NOAC activity.…”

Adherence to Rivaroxaban, Dabigatran, and Apixaban for Stroke Prevention for Newly Diagnosed and Treatment-Naive Atrial Fibrillation Patients: An Update Using 2013-2014 Data

“…This may be because of the once daily dosing of rivaroxaban and warfarin, which has been shown to be an important consideration for patients and physicians and may be even more important for patients who tend to be less adherent. 7,16 …”

Drug Adherence in Patients With Nonvalvular Atrial Fibrillation Taking Non-Vitamin K Antagonist Oral Anticoagulants in Turkey: NOAC-TR

“…[3][4][5][6][7] Rapid onset of action, stable fixed-dose combination, and the absence of the need for monitoring are their main advantages of NOACs over VKAs. 8,9 Because of these features of NOACs, the frequency of outpatient follow-up visits is lower. Due to their short half-life, the efficacy of NOACs may disappear quickly if the dose is missed.…”