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\begin{document}

\title{Determinants for under- and overdosing of direct oral anticoagulants and
physicians' implementation of clinical pharmacists' recommendations}



\author[1]{Souad Moudallel}%
\author[1]{Pieter Cornu}%
\author[1]{Alain Dupont}%
\author[1]{Stephane Steurbaut}%
\affil[1]{Vrije Universiteit Brussel}%


\vspace{-1em}



  
  \date{May 21, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
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\textless{}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 na\selectlanguage{ngerman}ïve(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\textless{}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.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\emph{Determinants for under- and overdosing of~direct oral
anticoagulants and~physicians' implementation~of clinical pharmacists'
recommendations}

Souad Moudallel\textsuperscript{1*}, Pieter Cornu\textsuperscript{1},
Alain Dupont\textsuperscript{1**}, Stephane
Steurbaut\textsuperscript{1**}

\textsuperscript{1}Research 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.

\emph{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.

\emph{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.

\emph{Results} : In 16.9\% of patients, inappropriate prescribing was
observed. For all DOACs considered together, body weight\textless{}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 na\selectlanguage{ngerman}ïve(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\textless{}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.

\emph{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)\textsuperscript{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
medications\textsuperscript{2-4}. 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
patients\textsuperscript{3, 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 \textsuperscript{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 \textsuperscript{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
\textsuperscript{2}. According to the literature, pharmacists can help
patients and providers in preventing and managing DOAC related
problems\textsuperscript{21-23}. 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
general\textsuperscript{1, 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 \textsuperscript{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

\emph{Study design and study population}

This was a cross-sectional study conducted at the UZ Brussel, a 721-bed
university hospital in Brussels, Belgium. Via the prescription order
validation tool, a tool that is used by clinical pharmacists to assess
the appropriateness of drug prescriptions with a main focus on high risk
medications (HRM), we identified all hospitalized patients who were
initiated on or continued with dabigatran, rivaroxaban, apixaban or
edoxaban between 1 January 2019 and 31 December 2019.

Patient demographic data (age, gender, weight, body mass index (BMI)),
co-medication, co-morbidities (hypertension, heart failure, diabetes
mellitus, cerebrovascular disease), most recent laboratory data at the
time of the DOAC prescription in the hospital (renal function, liver
parameters, anemia, thrombocytopenia),
CHA\textsubscript{2}DS\textsubscript{2}-VASc and HAS-BLED scores, DOAC
type and dosage, bleeding history, surgical procedures during hospital
stay, whether or not the DOAC was already initiated before hospital
admission, concomitant use of antiplatelet agents, P-glycoprotein and
cytochrome P450 3A4 inhibitors and inducers were collected via manual
chart review. Creatinine clearance (CrCl) was calculated via the
Cockcroft-Gault equation. Drug interactions were assessed according to
the 2018 European Heart Rhythm Association (EHRA) guidelines. In case a
patient was hospitalized more than once in 2019, only the \selectlanguage{english}first
prescription of the first admission was taken into account. Data
collection was performed by one investigator (M.S.) for consistency.

\emph{Outcomes}

The primary outcome was the percentage of patients with an inappropriate
DOAC initiated at or continued during hospital admission together with
the identification of determinants associated with DOAC under- and
overdosing. Similar to our previous study \textsuperscript{3},
rivaroxaban was used as the reference category. Secondary outcomes
included the quantification of the physicians' acceptance and
implementation rate of the clinical pharmacists' interventions as well
as the documentation of their non-acceptance and/or non-implementation.
An inappropriate DOAC dose was defined as a deviation from the
recommended dose in the SmPC. Underdosing was defined as the prescribing
of a reduced DOAC dose despite the patient not meeting the dose
reduction criteria. Overdosing was defined as the prescribing of the
standard DOAC dose despite the patient meeting the dose reduction
criteria. A contraindication was defined as a situation for which the
prescription of the DOAC was inadvisable.

If an intervention by a clinical pharmacist was deemed necessary, the
prescribing hospital physician was contacted by telephone after which
the pharmacists' recommendations were documented in the patient's
electronic medical record. General practitioners (GP) and/or community
pharmacists involved in the patient's care were contacted if the
prescribing hospital physician was unreachable, when more information
was needed, or in case the patient was already discharged.

\emph{Statistical analysis}

Descriptive and statistical analyses were carried out with IBM SPSS
Statistics version 27 (IBM Corp., Armonk, NY, USA). The
Kolmogorov--Smirnov test was used to test the normality of the
continuous variables. Histograms were evaluated to assess normality.
Categorical variables were expressed as percentages and continuous
variables as medians with interquartile ranges (IQRs). Differences in
the continuous variables among the four DOACs were evaluated using the
Kruskal-Wallis test. The Chi-square test was used to compare categorical
variables. A two-sided signi\selectlanguage{english}ficance level of 0.05 was used. Binary
logistic regression analysis was conducted to determine factors
associated with the under- and overdosing of the DOACs. Factors that
were significantly associated in the univariable analysis
(p\textless{}0.1) were included in the multivariable logistic regression
analysis. For the logistic regression models a corrected p-value
\textless{}0.05 (Benjamini-Hochberg correction for multiple comparisons)
was used, goodness of \selectlanguage{english}fit was assessed (R\textsuperscript{2}, receiver
operator characteristics curve) and residuals were reviewed. The odds
ratios (OR) were reported with their 95\% confidence intervals (CI).

Results

A total of 1688 consecutive and unique AF patients were included for
which the characteristics per DOAC are shown in table 1. Apixaban was
the most prescribed DOAC (34.7\%) followed by edoxaban (32.7\%),
rivaroxaban (23.8\%) and dabigatran (8.8\%). Apixaban users were
significantly older (median 81.0 years), weighed significantly less
(median 70.1 kg) and had a statistically lower renal function (median
52.0 mL/min) compared to users of another DOAC. Moreover, apixaban users
were diagnosed more often with arterial hypertension (73.0\%) and heart
failure (HF) (35.5\%). Combination with at least one antiplatelet drug
was observed in 23.6\% and 21.8\% of rivaroxaban and apixaban users,
respectively. Dual antiplatelet therapy was the highest in the apixaban
group (3.2\%).

The overall inappropriate prescribing rate in this study was 16.9\%
(n=286) with the highest underdosing and overdosing rates seen in the
apixaban (14.2\%) and rivaroxaban (9.7\%) group, respectively (Figure
1). Overall, underdosing, overdosing and contraindications were seen in
9.7\%, 6.9\% and 0.4\% of patients, respectively.

Considering the four DOACs together (see Table 2), a body weight
\textless{}60 kg (adj. OR 0.46, 95\% CI 0.27-0.77), the use of edoxaban
compared to rivaroxaban (adj. OR 0.42, 95\% CI 0.24-0.74), undergoing
surgery (adj. OR 0.57, 95\% CI 0.37-0.87), and being DOAC naive (adj. OR
0.45, 95\% CI 0.29-0.71) were associated with a significantly lower odds
of underdosing. On the other hand, having a bleeding history (adj. OR
1.86, 95\% CI 1.24-2.80) and the use of narcotic analgesics (adj. OR
1.67, 95\% CI 1.13-2.46) were associated with a significantly higher
odds of underdosing. Determinants associated with a higher odds of
overdosing were renal impairment (adj. OR 11.29, 95\% CI 6.23-20.45) and
a body weight \textless{}60 kg (adj. OR 2.34, 95\% CI 1.42-3.85),
whereas the use of dabigatran (adj. OR 0.24, 95\% CI 0.08-0.71) and
apixaban (adj. OR 0.18, 95\% CI 0.10-0.32) were associated with a lower
odds of overdosing compared to rivaroxaban.

For rivaroxaban (adj. OR 100.95, 95\% CI 23.23-438.70) and edoxaban
(adj. OR 3.25, 95\% CI 1.49-7.12) users, a decreased renal function was
associated with a higher odds of overdosing compared to patients with a
normal renal function. For rivaroxaban, we observed a lower odds of
underdosing in patients with a CrCl \textless{}50 mL/min (adj. 0.17,
95\% CI 0.06-0.48).

A lower body weight was a risk factor for underdosing in apixaban users
(adj. OR 0.26, 95\% CI 0.12-0.55), whereas this factor was associated
with a higher odds of overdosing in the edoxaban group (adj. OR 4.16,
95\% CI 1.97-8.77). Having a history of bleeding (adj. OR 2.14, 95\% CI
1.22-3.75) in apixaban users was associated with a higher odds of
underdosing.

Of the 286 identified AF patients with an inappropriate DOAC dose, the
physician was contacted by telephone in 226 (79.0\%) cases of which 131
and 90 calls concerned underdosed and overdosed prescriptions,
respectively. Five cases of dabigatran use and a CrCl \textless{}30
mL/min were classified as a contraindication. In addition, telephone
calls were conducted for eight cases concerning drug interactions (not
shown in figure 2) with rifampicin (n=5), carbamazepine (n=2) and
cyclosporine (n=1). Physicians accepted the pharmacists' advice in 179
cases (79.2\%) which consisted of 92 (51.4\%) advices for underdosing,
82 (45.8\%) for overdosing and 5 (2.8\%) for contraindicated dosages.
Regarding the non-accepted interventions (n=47), it concerned 39
(83.0\%) underdosed and 8 (17.0\%) overdosed cases. The advices were
effectively implemented, as evidenced by a correction of the
prescription in the patient's electronic medical record, for 75 out of
92 (81.5\%) underdosed, 69 out of 82 (84.1\%) overdosed and 4 out of 5
(80.0\%) contraindicated cases, a total of 148 cases (65.5\%).
Non-implemented advices, for which the reasons are listed in figure 2,
were observed for 15 underdosed, 11 overdosed and 1 contraindicated
case. For 2 underdosed as well as 2 overdosed cases we were unable to
track whether the intervention was implemented or not

Discussion

Despite their increased use and substantial research focusing on their
effectiveness and safety in clinical practice, appropriate DOAC
prescribing remains a problem as also evidenced by our
study\textsuperscript{24, 25}. Inappropriate first DOAC prescriptions
were found in 16.9\% of the patients, with underdosing being more
prevalent than overdosing. This is in line with a previous study
conducted at our institution \textsuperscript{3} as well as other
studies\textsuperscript{1, 2, 7-10}. The dosing recommendations differ
depending on the DOAC, with some of them requiring dose reductions based
solely on renal function and others taking additional criteria into
consideration. The high underdosing rate found in apixaban users seems
clinically relevant as underdosing with this DOAC was reported to be
associated with a nearly 5-fold increased stroke risk in AF
patients\textsuperscript{26}. On the other hand, it has been reported in
a prospective study that hydrophilic drugs like DOACs in frail older
patients with low muscle mass can lead to supratherapeutic DOAC plasma
levels, placing them at higher risk for major bleeding
complications\textsuperscript{27}.

Among patients prescribed DOACs, those receiving apixaban had a lower
renal function, were older and weighed significantly less compared to
users of other DOACs. According to recent literature, including a
systematic review in frail AF patients, apixaban was associated with a
lower risk of major bleedings compared to rivaroxaban and dabigatran,
although their effectiveness was comparable \textsuperscript{28-31}. As
shown in a registry of rivaroxaban users, renal impairment was a risk
factor for experiencing major bleeding events \textsuperscript{32}. The
risk of major bleedings was comparable between apixaban and
edoxaban\textsuperscript{29}. Intra DOAC comparisons still need to be
confirmed by findings from randomized controlled trials that are
expected to be released in the upcoming years e.g., the DARING-AF trial
and DANNOAC-AF trial \textsuperscript{28, 29}.

According to the literature, physicians may place more value on the
avoidance of bleeding in high risk AF patients, especially in those with
a high fall and bleeding risk \textsuperscript{3, 33, 34}. Results of
previous studies suggest an increased risk of falls and fractures among
older adults using opioids \textsuperscript{35, 36}. Walenga and
colleagues describe that the relative rate of clinically relevant
bleedings with the use of opioids was nearly twofold greater with low
dose rivaroxaban compared with enoxaparin \textsuperscript{37}.

The higher OR for underdosing apixaban in patients with a lower weight
may be related to the fact that weight is often used as a single
criterion for dose reduction in apixaban, while this is only to be
adapted in combination with an age \selectlanguage{english}[?]80 years and/or serum creatinine
\selectlanguage{english}[?]1.5 mg/dL.

The association of weight with overdosing in edoxaban users is mainly
due to younger patients with a weight \textless{}60 kg who were
hospitalized to undergo an ablation.

The association between a reduced CrCl and the higher odds to receive a
supratherapeutic dose as found for rivaroxaban and edoxaban users could
be due to a fluctuating renal function or physicians being unaware of
the CrCl threshold for dose adjustment \textsuperscript{2}.

A high percentage of the advices by the clinical pharmacists was
immediately accepted (79.2\%) and effectively implemented (65.5\%) by
the physicians. The accepted advices consisted for 79.9\% of
prescriptions for DOACs that were initiated prior to the hospital
admission. Physicians acknowledged that they did not consistently check
the DOAC dose upon admission due to a lack of time. A history of
bleeding and a fluctuating renal function were the most important
factors why advices to adjust the dose were not accepted. Some
physicians, less familiar with anticoagulation, preferred to discuss the
proposed dosage adjustment with the GP/cardiologist. In some cases, as
depicted in figure 2, renal function altered during hospitalization so
no adjustment was needed anymore, even if the advice was already
accepted. Other important reasons retrieved from the medical record for
non-implementation of accepted advices were the patients' bleeding risk
(n=2) and concomitant use of antiplatelet drugs (n=2). Despite the
initial acceptance, physicians chose to keep the reduced DOAC dose in
these cases after consultation with the head of department. After
implementation of the recommended dose adjustments, the total
inappropriate prescribing rate according to the SmPC was 8.2\% vs. the
initial 16.9\%, keeping in mind most of these off-label doses were
intentional due to the abovementioned reasons.

Some institutions have an integrated pharmacist-led DOAC service or
antithrombotic stewardship programs with the aim of improving the safety
and efficacy of DOAC use through identification and resolution of dosing
errors, patient education, improved patient follow-up and laboratory
monitoring \textsuperscript{16, 20, 22, 38, 39}. Studies showed that
such services increase appropriate DOAC dosing at baseline and
follow-up, which is in line with the recommendations of organizations
like EHRA and the American College of Cardiology
(ACC)\textsuperscript{38, 40, 41}. Clinical pharmacists are well
positioned to provide recommendations regarding the DOAC choice and
dose, presence of a contraindication as well as potential drug-drug and
drug-disease interactions \textsuperscript{20}. They are also able to
inform physicians of patients who may not be the best candidates for
DOACs (e.g., extremes of body weight, severe renal
impairment)\textsuperscript{16}. In addition, they also provide
motivational interviewing to promote patient understanding of DOAC
therapy and emphasize the importance of DOAC adherence
\textsuperscript{38}.

Involvement of clinical pharmacists should be more mainstream in the
hospitals, especially for HRM such as DOACs. Quintens et al. highlighted
the greater impact of advices given by telephone since half of the
advices were not accepted/read if only an electronic note was
left\textsuperscript{20}. In addition, a study of Dreijer et al.
conducted in patients using anticoagulants showed that implementation of
a multidisciplinary antithrombotic team over time significantly reduces
adverse drug reactions (ADRs) like bleedings or thrombotic events from
hospitalization until three months after hospitalization and resulted in
a lower all-cause mortality \textsuperscript{42}.

A useful recommendation for physicians could be to clearly document the
rationale for deviating from the approved dose in the patient's medical
record to avoid unnecessary phone calls. Physicians should be aware of
the most common mistakes concerning DOAC
prescriptions\textsuperscript{14}.

To our knowledge, this is the first study to assess determinants for
DOAC under- and overdosing in AF patients, nevertheless there are
limitations to our study. First, this was a single center study,
therefore the results may not be generalizable to other populations. Due
to the cross-sectional nature of our study, only the initial DOAC
prescription of a patient was taken into account. However, the
conditions necessitating a DOAC change or dose adaptation during
hospitalization were only present in a minority of patients. We also did
not examine the effect of inappropriate dosing and the dose adaptations
on the thromboembolic/bleeding event rate. In addition, our results may
be biased by inaccurate or incomplete information in the electronic
medical records. Further, this study was neither directed to identify
high risk AF patients who did not receive oral anticoagulants, nor to
assess DOAC adherence.

Additional research regarding the long term effects of the clinical
pharmacists' interventions is needed. Lastly, it would be of interest
for future research to focus on the interventions with the highest
impact on patient outcomes and to investigate which patients would
benefit most from the implementation of a multidisciplinary clinical
DOAC service.

In conclusion, in this study where for the first time determinants for
under- and overdosing of DOACs were assessed, inappropriate DOAC
prescribing was found to be still common. Interventions by clinical
pharmacists can reduce this burden. We recommend that clinical services
led by pharmacists play a greater role in assisting physicians during
the prescription process of high risk medications such as DOACs, in
order to reduce the number of inadequate prescriptions.

\emph{Conflict of Interest}

The authors declare that they do not have a conflict of interest.

\emph{Data availability statement}

The datasets used and/or analysed during the current study are available
from the corresponding author on reasonable request.

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Table 1 Baseline characteristics of the hospitalized AF patients per
DOAC. IQR= interquartile range; BMI= body mass index; SSRIs= selective
serotonine reuptake inhibitors.\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{Characteristics}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{RIVAROXABAN} \textbf{(n=402)}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{DABIGATRAN} \textbf{(n=148)}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{EDOXABAN} \textbf{(n=552)}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{APIXABAN} \textbf{(n=586)}\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Age (years), median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
77.0 (70.0-84.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
76.0 (68.0-84.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
72.0 (60.0-82.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
81.0 (72.0-87.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Male gender, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
240 (59.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
85 (57.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
316 (57.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
285 (48.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Weight (kg), median (IQR) \textless{}60 kg, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
78.9 (67.0-90.0) 48 (11.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
79.0 (67.0-90.0) 18 (12.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
77.0 (65.0-89.3) 78 (14.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
70.1 (59.5-85.0) 147 (25.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01 \textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
BMI (kg/m\textsuperscript{2}), median (IQR) BMI \textless{}18
kg/m\textsuperscript{2}, n (\%) BMI \textgreater{}30
kg/m\textsuperscript{2}, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
27.3 (24.0-31.0) 8 (2.0) 116 (28.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
27.0 (24.2-30.9) 1 (0.7) 43 (29.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
26.6 (23.0-30.1) 17 (3.1) 135 (24.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
25.4 (22.0-29.7) 28 (4.8) 127 (21.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01 0.02 0.04\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Residential care center, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
40 (10.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
20 (13.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
42 (7.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
91 (15.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Preadmission medication, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
328 (81.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
127 (85.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
295 (53.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
410 (70.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Surgery during hospital stay, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
159 (39.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
54 (36.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
255 (46.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
156 (26.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Bioprosthetic heart valve n, (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
31 (7.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4 (2.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23 (4.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
31 (5.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.04\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Renal function (mL/min), median (IQR) \textless{}30 mL/min, n (\%) 30-49
mL/min, n (\%) [?]50 mL/min, n (\%) Missing, n (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
67.0 (48.0-88.0) 25 (6.2) 82 (20.4) 291 (72.4) 4 (1.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
69.0 (51.5-91.5) 6 (4.1) 26 (17.6) 113 (76.4) 3 (2.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
76.0 (53.0-104.0) 22 (4.0) 83 (15.0) 442 (80.1) 5 (0.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
52.0 (36.0-74.0) 86 (14.7) 189 (32.3) 307 (52.4) 4 (0.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01 \textless{}0.01 \textless{}0.01 \textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Co-morbidities n, (\%) Hypertension Diabetes Heart failure Cancer\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
280 (69.7) 112 (27.9) 112 (27.9) 45 (11.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
105 (70.9) 36 (24.3) 42 (28.4) 8 (5.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
352 (63.8) 113 (20.5) 122 (22.1) 42 (7.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
428 (73.0) 153 (26.1) 208 (35.5) 68 (11.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01 0.04 \textless{}0.01 0.03\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Co-medication n, (\%) Lipid lowering Levothyroxine Gastrointestinal
Narcotic analgesics Benzodiazepines SSRIs\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
172 (42.8) 60 (14.9) 195 (48.5) 103 (25.6) 104 (25.9) 31 (7.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
83 (56.1) 18 (12.2) 71 (48.0) 43 (29.1) 37 (25.0) 20 (13.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
225 (40.8) 53 (9.6) 212 (38.4) 91 (16.5) 119 (21.6) 40 (7.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
244 (41.6) 97 (16.6) 294 (50.2) 104 (17.7) 148 (25.3) 60 (10.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01 \textless{}0.01 \textless{}0.01 \textless{}0.01 0.42
0.06\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Concomitant use of antiplatelets n, (\%) Aspirin Clopidogrel Ticagrelor
Aspirin + clopidogrel Aspirin + ticagrelor\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
95 (23.6) 72 (17.9) 15 (3.7) / 6 (1.5) 2 (0.5)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
18 (12.2) 12 (8.1) 4 (2.7) 1 (0.7) 1 (0.7) /\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
86 (15.6) 66 (12.0) 14 (2.5) / 6 (1.1) /\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
128 (21.8) 78 (13.3) 30 (5.1) 1 (0.2) 19 (3.2) /\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Thrombocytopenia n, (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
57 (14.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
25 (16.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
60 (10.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
97 (16.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.04\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Anaemia n, (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
198 (49.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
61 (41.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
172 (31.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
277 (47.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
History of bleeding n, (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
56 (13.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
14 (9.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
58 (10.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
100 (17.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
CHA\textsubscript{2}DS\textsubscript{2}-VASc, median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4 (3-5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4 (3-5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3 (2-5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4 (3-5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
HASBLED, median (IQR)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2 (1-3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2 (2-3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2 (1-3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2 (2-3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Table 2 Significant (white) and non-significant (grey) determinants for
under- and overdosing for all DOACs and per DOAC. DOAC= direct oral
anticoagulant; REF= reference category; adj. OR= adjusted odds ratio;
CI= confidence interval; CrCl= creatinine clearance. The p-value was
corrected with Benjamini-Hochberg correction for multiple testing.\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\emph{Determinants UNDERDOSING}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\emph{Corrected p-value}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\emph{Adj. OR}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\emph{95\% CI}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\emph{Determinants OVERDOSING}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\emph{Corrected p-value}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\emph{Adj. OR}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\emph{95\% CI}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
All DOACs\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
All DOACs\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
All DOACs\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
All DOACs\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
All DOACs\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
All DOACs\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
All DOACs\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
All DOACs\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Age [?]80 years\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.43\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.83\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.56-1.21\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Age [?]80 years\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.16\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.60\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.36-1.02\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Benzodiazepines\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.34\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.22\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.84-1.78\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male sex\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.90\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.19\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.72-1.97\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Diabetes\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.64\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.09\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.73-1.63\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Surgery\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.16\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.61\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.35-1.06\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
CHA\textsubscript{2}DS\textsubscript{2}-VASc\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.08\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.17\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.05-1.30\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
CHA\textsubscript{2}DS\textsubscript{2}-VASc\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.43\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.92\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.76-1.10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Heart failure\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.55\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.12\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.77-1.64\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Weight \textless{}60 kg [?]60 kg (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2.34\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.42-3.85\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Weight \textless{}60 kg [?]60 kg (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.02\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.46\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.27-0.77\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
DOAC Dabigatran Apixaban Rivaroxaban (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.04 \textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.24 0.18\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.08-0.71 0.10-0.32\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
DOAC Edoxaban Rivaroxaban (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.42\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.24-0.74\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Renal function (CrCl) \textless{}50 mL/min [?]50 mL/min (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
11.29\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
6.23-20.45\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Surgery\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.05\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.57\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.37-0.87\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Narcotic analgesics\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.04\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.67\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.13-2.46\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Bleeding history\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.02\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.86\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.24-2.80\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Initiation at hospital\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.45\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.29-0.71\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
DABIGATRAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
DABIGATRAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
DABIGATRAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
DABIGATRAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
DABIGATRAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
DABIGATRAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
DABIGATRAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
DABIGATRAN\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Diabetes\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.14\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2.79\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.94-8.29\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Weight \textless{}60 kg [?]60 kg (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.27\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4.14\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.48-35.49\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Narcotic analgesics\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.06\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
3.52\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.23-10.12\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Renal function (CrCl) \textless{}50 mL/min [?]50 mL/min (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.16\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
8.08\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.73-88.84\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
RIVAROXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
RIVAROXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
RIVAROXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
RIVAROXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
RIVAROXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
RIVAROXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
RIVAROXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
RIVAROXABAN\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Surgery\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.30\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.63\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.30-1.32\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Age [?]80 years\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.16\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.43\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.16-1.14\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Bleeding history\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.29\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.68\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.74-3.77\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Weight \textless{}60 kg [?]60 kg (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.48\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.47\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.60-3.62\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Initiation at hospital\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.08\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.21\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.05-0.91\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
CHA\textsubscript{2}DS\textsubscript{2}-VASc\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.26\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.82\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.62-1.09\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Age [?]80 years\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.06\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2.34\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.15-4.74\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Renal function (CrCl) \textless{}50 mL/min [?]50 mL/min (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
100.95\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
23.23-438.70\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Renal function (CrCl) \textless{}50 mL/min [?]50 mL/min (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.17\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.06-0.48\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
APIXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
APIXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
APIXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
APIXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
APIXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
APIXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
APIXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
APIXABAN\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Hypertension\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.46\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.32\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.72-2.43\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Age [?]80 years\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.51\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.62\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.19-2.07\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Diabetes\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.21\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.50\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.89-2.52\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Weight \textless{}60 kg [?]60 kg (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.56\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.34\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.57-3.19\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Renal function (CrCl) \textless{}50 mL/min [?]50 mL/min (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.08\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.80\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.06-3.04\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Renal function (CrCl) \textless{}50 mL/min [?]50 mL/min (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.08\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4.37\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.13-16.91\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Heart failure\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.08\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.78\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.07-2.96\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Surgery\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.26\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.25\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.03-1.92\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Weight \textless{}60 kg [?] 60 kg (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.26\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.12-0.55\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Heart failure\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.64\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.27\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.52-3.10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Bleeding history\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.03\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
2.14\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.22-3.75\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
CHA\textsubscript{2}DS\textsubscript{2}-VASc\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.90\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.98\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.68-1.41\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
HAS-BLED\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.26\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.42\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.85-2.35\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
EDOXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
EDOXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
EDOXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
EDOXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
EDOXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
EDOXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
EDOXABAN\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
EDOXABAN\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Surgery\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.20\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.36\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.10-1.33\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Surgery\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.13\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.48\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.20-1.18\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Initiation at hospital\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.12\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.36\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.12-1.03\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
CHA\textsubscript{2}DS\textsubscript{2}-VASc\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.23\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.79\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.58-1.08\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
HAS-BLED\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.90\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.96\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.52-1.77\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
HAS-BLED\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.56\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.02\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.64-1.63\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
CHA\textsubscript{2}DS\textsubscript{2}-VASc\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.08\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.48\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.02-2.14\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Male sex\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.16\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.52\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.24-1.12\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Narcotic analgesics\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.08\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2.98\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.14-7.80\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Weight \textless{}60 kg [?] 60 kg (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textless{}0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4.16\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.97-8.77\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Renal function (CrCl) \textless{}50 mL/min [?]50 mL/min (REF)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
0.01\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
3.25\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
1.49-7.12\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Figure 1 Appropriate vs. inappropriate (contraindication, under-and
overdosing) prescribing rates per DOAC

Figure 2 Overview of the number of phone calls conducted for
inappropriate DOAC prescriptions, accepted advices and implemented
advices. Reasons for not contacting the physician in case of
inappropriate prescriptions as well as reasons for non-acceptance and
non-implementation of the pharmacists' interventions are listed in the
orange boxes. SAPT= single antiplatelet therapy; DAPT= dual antiplatelet
therapy; DOAC= direct oral anticoagulant; GP= general practitioner. *The
appropriateness of 7 prescriptions could not be assessed due to lack of
renal function data\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

