Determinants for under- and overdosing of direct oral anticoagulants and physicians’ implementation of clinical pharmacists’ recommendations
Souad Moudallel1*, Pieter Cornu1, Alain Dupont1**, Stephane Steurbaut1**
1Research Group Clinical Pharmacology and Clinical Pharmacy; Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Jette, Belgium
*Corresponding author. Laarbeeklaan 103, 1090 Jette, Belgium. Tel: +3224763385. E-mail address: Souad.Moudallel@vub.be
**Stephane Steurbaut and Alain Dupont should be considered joint senior authors
Running title: DOAC dosing/implementation of advices
Word count abstract: 246
Word count article: 2850
Number of References: 42
Number of Tables: 2
Number of Figures: 2
Key words: DOACs, clinical pharmacist, inappropriate prescribing, interprofessional collaboration
What is already known about this subject:
•       DOACs are increasingly used high risk medications for stroke prevention in atrial fibrillation and other indications.
•       DOAC prescribing is error prone given different dosage regimes depending on drug, indication and other factors.
•       Only determinants associated with inappropriate prescribing in general have been identified so far.
What this study adds:
•       Distinct determinants associated with under- and overdosing were identified and studied per DOAC.
•       Acceptance and implementation rates of interventions by clinical pharmacists were studied in detail and high.
•       Clinical services led by pharmacists help physicians to reduce the number of inadequate DOAC prescriptions.
Aim : To analyze the appropriateness of DOAC dosing and determinants for under-and overdosing as well as acceptance and implementation rates of interventions by clinical pharmacists.
Methods : Cross-sectional study from January 2019-December 2019 in a tertiary hospital in hospitalized patients with atrial fibrillation on DOACs (n=1688). Primary outcome was the proportion of patients with inappropriate DOAC prescribing with identification of determinants for under-and overdosing. Secondary outcomes included acceptance and implementation rates of pharmacists’ advices and determination of reasons for non-acceptance/non-implementation.
Results : In 16.9% of patients, inappropriate prescribing was observed. For all DOACs considered together, body weight<60 kg(OR 0.46 [0.27-0.77]), edoxaban use(OR 0.42 [0.24-0.74]), undergoing surgery(OR 0.57 [0.37-0.87]) and being DOAC naïve(OR 0.45 [0.29-0.71]) were associated with a significantly lower odds of underdosing. Bleeding history(OR 1.86 [1.24-2.80]) and narcotic use(OR 1.67 [1.13-2.46]) were associated with a significantly higher odds for underdosing. Determinants with a significantly higher odds of overdosing were renal impairment(OR 11.29 [6.23-20.45]) and body weight<60 kg(OR 2.34 [1.42-3.85]), whereas the use of dabigatran(OR 0.24 [0.08-0.71]) and apixaban(OR 0.18 [0.10-0.32]) were associated with a significantly lower odds of overdosing compared to rivaroxaban. Physicians accepted the pharmacists’ advice in 179 cases (79.2%) consisting of 92 (51.4%) advices for underdosing, 82 (45.8%) for overdosing and 5 (2.8%) for contraindications. The advices were effectively implemented for 75 (81.5%) underdosed, 69 (84.1%) overdosed and 4 (80.0%) contraindicated cases.
Conclusion: Inappropriate DOAC prescribing remains common. Clinical services led by pharmacists helps physicians to reduce the number of inadequate prescriptions for high risk medications such as DOACs.
Introduction
The direct oral anticoagulants (DOACs) are increasingly used as the treatment of choice for stroke prevention in atrial fibrillation (AF) and as treatment and prophylaxis of venous thromboembolisms (VTE)1, 2. DOACs are at least as effective as vitamin K antagonists (VKAs) and do not need routine monitoring, but also come with specific requirements and risks. DOACs require dosage adjustments for renal function, weight, age, and concomitant medications2-4. Several studies have shown that DOACs are frequently prescribed incorrectly with inappropriate dosing varying from 12.8% to 42.8% of AF patients as well as other patients3, 5-19. Inappropriate prescribing has been shown to be an independent risk factor for adverse drug events (ADE) leading to potential clinical consequences including thromboembolism, bleeding, hospitalization and death 1, 20. Older patients are especially susceptible to ADEs associated with inappropriate prescribing due to decreased drug metabolism, increased prevalence of hepatic/renal dysfunction, and the higher likelihood of drug-drug interactions as a result of polypharmacy 1. Although prescribers may have valid reasons for using dosages that deviate from the Summary of Product Characteristics (SmPC), no studies have demonstrated improved anticoagulation therapy outcomes associated with this practice. It is therefore important to consistently monitor DOAC prescriptions and identify any related patient safety issues 2. According to the literature, pharmacists can help patients and providers in preventing and managing DOAC related problems21-23. The purpose of this study was to assess the rate of inappropriate DOAC dosing and identify determinants associated with under- and overdosing. To the best of our knowledge, this hasn’t been investigated before since previous literature commonly has focused only on determinants for inappropriate prescribing in general1, 3, 11. Given the increasing prescription rates of DOACs (including edoxaban) over the last years, this study intended to yield additional information about possible determinants for under- and overdosing compared to the study of 2018 3. Moreover and also innovative in aim, we assessed the physicians’ acceptance and implementation rate of the pharmacists’ DOAC dosing advice with listing of the reasons for non-acceptance and non-implementation for the cases where the pharmacists’ advice was not followed.
Methods