Medication adherence and management of polypharmacy in primary care – From patient experiences to an interventional study with oral anticoagulants

Background
The concomitant use of several medicines (polypharmacy) is highly present in the population today. Polypharmacy is negatively associated with medication adherence. Effective management strategies and adherence-enhancing interventions are sought. Direct oral anticoagulants (DOAC) are high-risk medicines and due to their short half-life, timely intake of DOAC is crucial. Stroke patients with atrial fibrillation (AF) receive life-long DOAC therapies to prevent recurrent strokes. In primary care, those patients are often confronted with polypharmacy. Electronic monitoring allows a deep insight into the patients’ medication taking behaviour. Appropriate metrics are needed to evaluate medication intake from electronic monitoring data.
Therefore, the goal of this thesis was to explore medication adherence of anticoagulated patients with polypharmacy in primary care with the aim of operationalising medication adherence for an interventional study in stroke patients. It was achieved in three projects.
Methods and results
In project A1, we aimed at validating the usefulness of a simple screening method capable of detecting visual stability problems with repackaged medicines. We selected eight criteria for solid formulations from the International Pharmacopoeia. Twenty-four critical medicines were repackaged in MCA and stored at room temperature and accelerated conditions for 4 weeks. We observed six alterations at accelerated conditions. No alteration was observed at room temperature, except for the chipping of tablets that had been stuck to cold seal glue. We concluded that the eight criteria can detect alterations of the appearance of oral solid medicines repackaged in MCA.
With project A2, we aimed at better understanding patients' medication taking behaviour at home by getting insight into the medication management strategies. Structured interviews were performed with 137 patients in community pharmacies. A medication review and a multiple-choice questionnaire revealed that the majority of the patients used weekly (43.8%) or daily (12.4%) pillboxes. About 30% of the patients reported occasionally forgetting to take their medication. Thus, regardless of the management strategy, patients sometimes forget to take their medication and health care professionals should be aware that medication adherence remains a matter of concern.
Project A3 aimed at exploring medication management strategies in-depth and measuring adherence to DOAC. We therefore conducted interviews at the home of 18 elderly outpatients who were taking ≥4 medicines daily including a DOAC. The patients electronically recorded medication intake during 4 weeks. The interviews were thematically analysed. The participants combined at least five strategies, composed of internal (memory-based) and external (packaging-based or intake-based) strategies. Forgetting medication intake in spite of a management strategy was common. Missing the moment to adapt the strategies to ageing or cognitive decline emerged as most important limitation mentioned by the participants.
Project B describes the process of developing and evaluating an e-learning course for pharmacy students with the illustrative example of an e-learning course on OAC. We adapted a French e-learning course on OAC. We evaluated the course with Pharmacy students during their internship in community pharmacies. The evaluation was performed according to the levels of Kirkpatrick. The students gained knowledge in oral anticoagulation, were satisfied with the course, and wished to have more e-learning courses.
In project C1 we commented a systematic review and meta-analysis on medication adherence to DOAC. The authors of this publication analysed data of six studies that used different assessment methods of medication adherence with different definitions of adherence. In our opinion this highlights one problem of adherence research, where inconsistent definitions are used that lead to incomparable results.
Project C2 is the protocol for a randomised crossover study that aims at evaluating the effect of an educational, reminder-based adherence-improving intervention by electronically monitoring DOAC-treated stroke patients (MAAESTRO). Outpatients with polypharmacy including a DOAC monitor their medication intake for 6 months. Then they will receive pharmaceutical counselling with feedback on their medication intake and a MCA for the subsequent 6 months. They will receive reminders during either the first or the last 3 months after the counselling.
Project C3 gives first insights into the MAAESTRO study. Data from 41 patients who have finished the first 6 months of the MAAESTRO study were analysed. Mean taking and timing adherence exceeded 90%. Correct dosing occurred in 86.6% of the days. Seven patients (17.1%) had drug holidays. Patients with twice-daily regimen (70.7%) had higher taking adherence in the morning than in the evening (94.4% versus 89.9%; p = 0.001). Deviant intake patterns were common. This demonstrates that appropriate adherence metrics calculated from electronic monitoring data can reveal deviant intake behaviour.
Conclusion
To conclude, this thesis adds valuable information on mediation adherence of DOAC-treated stroke patients and medication management strategies of elderly outpatients taking DOAC. Adherence metrics discussed in this thesis can be used for future clinical trials. They can equally be used to provide feedback on medication adherence for patients in clinical practice and especially to community pharmacies offering filling of MCAs to their patients.