Journal of Pharmacovigilance

Can Electronic Medical Record be used for Reducing DOAC Prescription Errors in Inpatients?

Friederike Steffen, Constantin von zur Mühlen, Armin Nemani, Timo Heidt, Johannes Schulte, Christoph Bode and Marvin Krohn-Grimberghe^* Department of Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, Germany
^*Correspondence: Marvin Krohn-Grimberghe, Department of Cardiology and Angiology, University Heart Center Freiburg – Bad Krozingen, Germany, Tel: 76127034010, Email:

Received: 27-Jul-2021 Published: 21-Aug-2021, DOI: 10.35248/2329-6887.21.9.329

Introduction

The approval of the five direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban (not approved in every country) has expanded the options of oral thromboprophylaxis [1-3]. DOACs are used for the treatment and prophylaxis of deep vein thrombosis and pulmonary embolism as well as for stroke prevention in patients with non-valvular atrial fibrillation and other indications [3,4]. Current guidelines state that DOACs should not be combined with other drugs having anticoagulatory properties and should be paused before scheduled procedures that carry an increased bleeding risk [3] for healthcare systems. Of all medication classes, cardiovascular drugs are most frequently involved in MEs, and anticoagulants represent the largest portion within this class [5]. Furthermore, about half of anticoagulation-associated adverse drug events are caused by MEs [6]. Medication errors (MEs) can jeopardize patient safety and create enormous economic challenges. The WHO reports that MEs lead to 1.3 million injuries per year and cause on average one fatality per day in the USA [7]. The global annual costs are estimated at $42 billion or rather at about 1% of the total global health expenditure each year [7]. Several studies demonstrated a reduced number of MEs by using e-health systems [8–10]. Our study investigated whether adding color-highlighting of direct oral anticoagulants and antiplatelet drugs in an electronic medication chart can further reduce the number of MEs.

Methods

Chart reviews for DOACs and MEs prescription were performed three months before and three months after the introduction of a color scheme for highlighting medications with anticoagulatory or anti-platelet properties on the cardio logical wards of our university hospital in January 2018. Before the intervention, medications were grouped by route of administration in an alphabetical order without the use of color coding for specific drug classes. To reduce bias, no further intervention was performed and the treating physicians were not aware of the study. Treatments were independently classified by F. S. and M. K.-G. In case of disagreement, concerning cases were jointly discussed to reach agreement (about 5% of all cases). In the case of failed agreement, C. v. z. M. would have made the final decision. Since agreement was reached in all cases, the latter did not occur. The study was performed following national and international law as well as ethical standards and was approved by the ethics committee of the University of Freiburg (number 95/20).

Study population

A total of 2.107 consecutive inpatients treated on three cardio logical wards were screened three months before and three months after medication highlighting was introduced (before n= 1.045; after n= 1.062). Patients were included when they were under longterm DOAC treatment or had received a DOAC at any point of time during their hospital stay. Patients to whom a DOAC was not prescribed were excluded.

Classification

Patients were classified as having received either correct or incorrect co-prescriptions of anticoagulatory medications (e.g. incorrect simultaneous treatment with DOAC + lowmolecular- weight or unfractionated heparin (LMWH / UFH); DOAC + vitamin K antagonist (VKA); DOAC + 2^nd DOAC) or periinterventional handling (e.g. no DOAC therapy pausing while planned intervention or operation carrying high bleeding risk). Co-prescription of antiplatelet medications was deemed acceptable. Other possible forms of medication errors, such as incorrect dose adjustment in case of (chronic) renal failure, were not evaluated. Standard operating procedures of our institution do not recommend bridging of DOAC with LMWH before procedures with increased bleeding risk. Still, such bridging was deemed acceptable as long as no simultaneous treatment with both was found.

Data analysis

P-values were calculated by using fisher’s exact test for categorical and unpaired t-test for numerical variables. All tests were two-sided. Results were considered statistically significant at p<0.05. All calculations were performed by using Graph Pad Prism version 8.4.3.

Results

Patient Characteristics

Table 1 shows the demographic and clinical characteristics of the patients as well as the number of prescribed DOACs.

Discussion

Recent studies show an increasing rate of atrial fibrillation as well as other indication for oral anticoagulation [11-13]. Furthermore, the number of DOAC prescriptions expands, while the use of VKAs decreases [2,4,14,15]. These observations illustrate a great need for the development of strategies to prevent MEs during DOAC prescription. In our patient population nearly one in every four patients received DOAC, with rivaroxaban making up 77% of all cases. As a result, the majority of medication errors occurred with rivaroxaban. Herein the finding of our study is in line with other studies, as rivaroxaban was the most frequently prescribed DOAC in the ambulatory setting in the USA (48.2% of all DOACs prescriptions for patients with atrial fibrillation) and the most often registered DOAC in medication error reports [14,15]. Many MEs are associated with anticoagulants, and the majority of MEs happens during prescription writing [16,17]. We focused on cardiology wards where anticoagulants are among the most commonly prescribed and most error prone medications. Color highlighting could easily be tailored to the most commonly prescribed or potentially most harmful drug-class in each department or ward (e.g. chemotherapeutics on the haematooncology wards and immunosuppressant’s on the transplant wards). The color scheme led to a reduction of prescription errors from 8.2% to 2.2% in patients receiving DOAC (p= 0.0013). By using pre-post comparisons, Pontefract et al. [9] showed that computerized decision support is able to reduce MEs. Other studies have demonstrated a decreased number of MEs by using e-health systems [8,10]. Moreover, these studies revealed that the reduction of anticoagulation related MEs result in lower probability for clinically relevant complications, such as bleedings and thromboembolic events, as well as a significantly reduced hospitalization and mortality rate [10]. Since our study would be underpowered for detecting changes in clinical outcomes, we did not analyze the clinical consequences of MEs.

The most common reason for MEs was incorrect combination of two drugs with anticoagulatory properties. Most frequently rivaroxaban was incorrectly co-prescribed with LMWH. This kind of prescription error occurred mainly during the first days of an inpatient’s stay. Quite likely, doctors did not recognize that a patient’s medication plan already included a DOAC and accidentally co-prescribed subcutaneous LMWH for thromboembolism prophylaxis. This finding is in line with the results from the study by Rahmanzade et al. [18], which found that most erroneous duplication of anticoagulants happen during the first or last days of an inpatient’s stay. Similar to our findings, DOACs were frequently combined with NMWH in their patient population. The remaining prescription errors in our study occurred; when DOAC were not paused before interventions carrying increased bleeding risk. Henriksen et al. [17] report that most MEs in orally anti-coagulated patients occur when patients were admitted to or discharged from the hospital or when they were moved within the hospital (e.g. to a different ward to receive surgery or other interventions).

The intervention led to a greater reduction of errors related to perioperative and peri interventional pausing of DOACs than with double prescriptions. Thus, further interventions should be studied to further reduce the latter kind of medication error. For example, automated pop-up prompts could be integrated into the electronic health record to warn physician when they are about coprescribe LMWH to patients already treated with a DOAC.

Strengths and Limitations

Other forms of medication errors, such as incorrect dose adjustment in the case of reduced glomerular filtration rate, were not evaluated. It seemed unlikely that they would be affected by the color scheme and the electronic health record used in our hospital already included a tool that alerted doctors about incorrect or missing dose adjustments of medications during the medication prescription phase.

Strengths of the study are that data were independently analyzed by two persons and treating physicians were unaware of the study. Furthermore, our study impressively shows how a simple and costeffective method is able to significantly improve patient safety.

Conclusion

In summary, the rate of prescription errors could be reduced in patients receiving DOACs by highlighting medications with anticoagulatory properties in an electronic health record. Future research is needed to confirm these results and develop further tools to reduce prescription errors. The increasing availability of electronic health records lends itself to the incorporation of different tools for improving prescription. Not least the intervention studied here could be incorporated in electronic health records at very low costs and without further complicating the prescription process for treating physicians.

End-Matter

Contributor-ship

The study was planned and organized by M. K.-G.. F. S. and M. K.-G. Collected and analyzed data and wrote the manuscript. A. N. and J. S. assisted in data collection. C.

v. z. M., T. H. and C. B. assisted in writing the manuscript.

Declaration of conflicting interests

The authors declared no conflicts of interest concerning the research, authorship, and/or publication of this article.

Sources of funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Data availability

The raw data underlying this article cannot be shared publicly due to limitations set by the ethics committee of the University of Freiburg to protect the privacy of the participants of this study. Anonym zed versions of the data will be shared on reasonable request to the corresponding author.

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