Direct Oral Anticoagulants and Non-valvular Atrial Fibrillation: Compliance with Dose Level Guidelines in Patients Aged 80 Years and Over

Abstract

Background: Direct oral anticoagulants (DOACs) are currently recommended as first-line or (after vitamin K antagonists) second-line therapy for preventing stroke and systemic embolism in patients with non-valvular atrial fibrillation. In patients aged 80 years and over, however, the fear of DOAC-associated bleeding and the complexity of DOAC dosing regimes may prompt physicians to prescribe inappropriate dose levels.

Objective: The objective of this study was to determine compliance with French and European guidelines of doses of three DOACs (apixaban, dabigatran and rivaroxaban) prescribed to patients aged over 80 years in an indication of non-valvular atrial fibrillation, and to identify factors associated with poor compliance.

Methods: We performed a retrospective single-centre study of patients aged over 80 years routinely treated with a DOAC (apixaban, dabigatran or rivaroxaban) for non-valvular atrial fibrillation at Valenciennes General Hospital (Valenciennes, France) between 1 January, 2016 and 31 December, 2017. We determined compliance with French and European guidelines of DOAC doses as a function of each patient's clinical and laboratory parameters, and thus classified the regime as being appropriately dosed, overdosed or underdosed.

Results: A total of 703 patients (371 taking apixaban, 92 taking dabigatran and 240 taking rivaroxaban) were included in the study. We found that 274 patients (39%) had been prescribed an inappropriate DOAC regime, with underdosing in 241 cases (34%) and overdosing in 33 cases (5%). Underdosing mainly concerned the two most widely prescribed DOACs, i.e. apixaban (39% of all apixaban prescriptions were underdosed) and rivaroxaban (40%). Concomitant treatment with an antidepressant was associated with underdosing of rivaroxaban or apixaban (p = 0.0339). In contrast, initial management in a neurology department was associated with appropriate dosing (p = 0.000146) for both these DOACs.

Conclusions: Among patients with non-valvular atrial fibrillation aged 80 years and over, about 40% of DOAC prescriptions feature inappropriate dose levels. It might be possible to reduce inappropriate dosing by raising awareness among hospital-based and private-practice prescribers, providing prescription support tools for DOACs, and performing medication reconciliations and reviews at hospital and in private practice.