Challenges with appropriate prescribing of direct oral anticoalulants and recommendations to improve their rational use

Souad Moudallel

Research output: ThesisPhD Thesis


Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults and is associated with an increased risk of stroke, where anticoagulation therapy has proven to be effective and lifesaving. Although direct oral anticoagulants (DOACs) have become the first choice for stroke prevention in most patients with AF, several challenges occur with the use of these agents. After a general introduction in the first chapter and the aim and outline of this dissertation in the second chapter, chapter 3 discusses the rate of inappropriate prescribing in clinical practice first based on a retrospective study and later based on a prospective study we conducted in this regard. In addition, we assessed risk factors for under-and overdosing of DOACs in AF patients. Approximately 1 in 4 and 1 in 6 prescriptions for the retrospective and prospective study respectively showed prescribing patterns that are inconsistent with the summary of product characteristics (SmPC) with underdosing being more prevalent than overdosing. The complexity of appropriate DOAC dosing, depending on aspects such as therapeutic indication, co-medication, renal function and other patient-related factors such as age and/or weight, as well as the setting where therapy with DOACs is initiated (prehospital vs. hospital) contributed to prescribing errors. Underestimation of the necessity for dose reduction and insufficient attention for an impaired renal function may be explanations in case of overdosing, whereas fear for bleeding and insufficient knowledge of the set of conditions requiring a dose reduction may lead to underdosing. The European Heart Rhythm Association (EHRA) guidelines seem to be less strict than the SmPC and/or more pragmatic since a high proportion of the underdosed cases according to the SmPC were classified as conform with the EHRA guidelines. Due to the differences among the oral anticoagulants, it is crucial for health care professionals (HCPs) to use these drugs appropriately to achieve their safest and most efficacious use in optimizing patient outcomes. In the prospective study, we showed that interventions by clinical pharmacists can reduce inappropriate prescribing strengthening the recommendation that clinical services led by pharmacists can play an important role in assisting physicians during the prescription process of high-risk medications such as the DOACs. Almost 80% of the interventions by clinical pharmacists were accepted, implying that medication errors can be considered largely preventable.
Chapter 4 showed that the adherence rate to the DOACs among AF patients is suboptimal in approximately one in four patients. Assessment of risk factors for suboptimal DOAC adherence was associated with a perception of conflicting information communicated from HCPs to the patient, poor shared decision making (SDM) and a higher educational level of the patient. This implies that reinforced education of both patients and HCPs in combination with interprofessional collaboration may be potential solutions to prevent knowledge gaps in patients and the communication of conflicting
Summary177information. Further, our work highlighted the fact that patients should be empowered as partners in their care and that this could be achieved by using SDM procedures. It may be advantageous to dedicate time during consultations to talk about key issues in the decision to prescribe an anticoagulant as well as its use with attention to patients' reflections regarding these aspects. In an additional study, we showed that the suboptimal DOAC adherence found in another cohort was not related to patient satisfaction, nor to knowledge over a time period of 6 months. However, a strong correlation between treatment satisfaction and this knowledge was found. Knowledge gaps were identified that could be remediated through patient education and follow-up. To investigate the outcomes of such interventions on the knowledge level and adherence of AF patients treated with DOACs, larger and longer studies are needed. DOAC adherence can possibly be improved through patient education, behavioural interventions and engagement in a SDM process, implementation of anticoagulant monitoring services or structured pathways of care with a coordinated patient follow-up as managed within an antithrombotic stewardship program. In addition, utilization of technological aids and mobile health applications as well as the optimization of DOAC prescribing by HCPs through education, digital clinical decision support systems and electronic health records are possible strategies to improve adherence.
Chapter 5 discusses the results of the retrospective study using EudraVigilance data to compare the gastrointestinal (GI) safety profile of the DOACs dabigatran, rivaroxaban and apixaban. Half of the reported DOAC ICSRs were bleeding-related of which more than 25% were GI-related. Within the GI bleedings, in particular stomach-related bleedings, ulcer-related duodenal bleedings and rectal bleedings were often reported. The disproportionality data emerging from the comparison between the DOACs suggested that dabigatran may be more frequently involved in GI bleeding events compared to the other DOACs. Considering all the above mentioned study results together, this dissertation highlights the importance of an antithrombotic stewardship program and other measures to be taken to decrease the risk of harm associated with antithrombotic drugs and DOACs in particular. This program includes a multidisciplinary approach, focusing on different safety interventions including education of HCPs, medication reconciliation and medication reviews by clinical pharmacists, drafting local anticoagulant therapy guidelines as well as patient counselling at admission and discharge.
Original languageEnglish
QualificationDoctor of Pharmaceutical Sciences
Awarding Institution
  • Vrije Universiteit Brussel
  • Steurbaut, Stephane, Supervisor
  • Dupont, Alain, Supervisor
  • Cornu, Pieter, Co-Supervisor
Award date6 Sep 2022
Publication statusPublished - 2022


  • Atrial fibrillation
  • cardiac arrhythmia
  • adults
  • anticoagulation therapy
  • stroke
  • DOACs


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