Patient Preference and Adherence Dovepress

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ORIGINAL RESEARCH

Comparing quality of life and treatment

satisfaction between patients on warfarin and
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direct oral anticoagulants: a cross-sectional study

This article was published in the following Dove Press journal:
Patient Preference and Adherence

Diana Leh-Ching Ng 1 Introduction and aim: Patient quality of life (QOL) while on long-term oral anticoagulant
Gin-Gin Gan 2 therapy has been receiving greater attention in recent years due to the increase in life
Chee-Shee Chai 1 expectancy brought about by advances in medical care. This study aimed to compare the
Kok-Han Chee 2 QOL, treatment satisfaction, hospitalization and bleeding rate in patients on long-term
For personal use only.

warfarin versus direct oral anticoagulants (DOAC).

Kok-Leng Tan 3
Methods: This was a cross-sectional study of patients with non-valvular atrial fibrillation
Seng-Beng Tan 2
(NVAF) or venous thromboembolism (VTE) on long-term anticoagulant therapy attending
Ping-Chong Bee 2
the cardiology clinic and anticoagulation clinic of the University Malaya Medical Centre
1
Department of Medicine, Faculty of from July 1, 2016, to June 30, 2018. Patient QOL was assessed by using the Short Form 12
Medicine and Health Science, University
Malaysia Sarawak, Kota Samarahan,
Health Survey (SF12), while treatment satisfaction was assessed by using the Perception of
Sarawak, Malaysia; 2Department of Anticoagulation Treatment Questionnaire 2 (PACT-Q2).
Medicine, Faculty of Medicine, University Results: A total of 208 patients were recruited; 52.4% received warfarin and 47.6% received
of Malaya, Kuala Lumpur, Malaysia;
3
Department of Medicine, Faculty of DOAC. There was no significant difference in QOL between warfarin and DOAC based on
Medicine, University Science Malaysia, SF12 (physical QOL, P=0.083; mental QOL, P=0.665). Nevertheless, patients in the DOAC
Penang, Malaysia group were significantly more satisfied with their treatment compared to the warfarin group
based on PACT-Q2 (P=0.004). The hospitalisation rate was significantly higher in the
warfarin group than the DOAC group (15.6% versus 3.0%, P=0.002). Clinically relevant
minor bleeds and severe bleeding events were non-significantly higher in the warfarin group
than the DOAC group (66.7% versus 40.0%, P=0.069).
Conclusion: Compared to warfarin, treatment of NVAF and VTE with DOAC showed
comparable QOL, higher treatment satisfaction, lesser hospitalization, and a non-significant
trend toward fewer bleeding episodes.
Keywords: quality of life, treatment satisfaction, convenience, warfarin, direct oral
anticoagulants

Introduction
Warfarin, a vitamin K antagonist, has been widely used for decades to treat or
prevent stroke and systemic embolism in patients with atrial fibrillation (AF) or
venous thromboembolism (VTE). Warfarin has narrow therapeutic index, which
Correspondence: Gin-Gin Gan requires frequent international normalized ratio (INR) monitoring to prevent bleed-
Department of Medicine, Faculty of ing complications and to maintain therapeutic efficacy. The target range of INR
Medicine, University of Malaya, Kuala
Lumpur 50603, Malaysia may vary depending on the indications for anticoagulation.1,2 The use of warfarin is
Tel +60 37 949 2741 challenging, as there is considerable interpatient variability in the daily maintenance
Fax +60 37 955 6936
Email [email protected] dose of warfarin. In addition, numerous foods and drugs as well as alcohol are

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and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work
http://doi.org/10.2147/PPA.S204246
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 Ng et al Dovepress

known to interact with the metabolism of warfarin.3 Methodology

Genetic variation in the metabolism of warfarin also has
Study design
been shown to affect its efficacy.4 Despite these chal-
This was a cross-sectional study comparing QOL and
lenges, warfarin is still a commonly used oral anticoagu-
treatment satisfaction in patients receiving long-term war-
lant, mainly due to its affordability and availability.
farin or DOAC attending the cardiology clinic and antic-
Direct oral anticoagulants (DOAC) such as dabigatran,
oagulation clinic of University Malaya Medical Centre
rivaroxaban, apixaban and edoxaban have been developed
(UMMC) from 1st July 2016 to 30th June 2018. All
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to overcome the challenges of using warfarin. Dabigatran

patients were aged 18 years and above, and had been
is a direct inhibitor of Factor IIa, while rivaroxaban, apix-
treated with the same oral anticoagulant for at least 6
aban and edoxaban are direct inhibitors of Factor Xa.5 The
months. Patients were categorized as receiving DOAC if
advantages of DOAC include simple dosing without the
they were treated with dabigatran, rivaroxaban or apixa-
need for monitoring, no need for dietary restriction, fewer
ban. Indications for warfarin and DOAC in these patients
drug–drug interactions, a rapid onset of action and a
include underlying non-valvular AF (NVAF) or VTE.
shorter half-life which allows for the possibility of uncom-
Patients were excluded in the case of underlying issues
plicated switching or bridging therapy.6 Nevertheless,
such as mechanical heart valves, valvular heart disease,
these drugs are expensive and require strict adherence to
malignancy, concomitant anti-platelet therapy, cross-over
the treatment due to its fast offset of action. Being newer
from warfarin to DOAC or vice-versa, hospital admission
oral anticoagulants, there is still limited evidence on the
within 1 month of the interview due to any cause other
For personal use only.

usage of DOAC in conditions such as antiphospholipid

than complications with their oral anticoagulant, or cogni-
syndrome and valvular heart disease, nor are the risks
tive/visual impairments that restricted patients from
involved with prosthetic heart valves and susceptible
answering questionnaires independently. Patients who
populations clearly known.5 The reversal agents for these
were treated with warfarin but had an incomplete INR
newer agents are not widely available and are more expen-
record were also excluded. This study was approved by
sive than using vitamin K for warfarin.
the Ethics Committee of UMMC. Written informed con-
Patient quality of life (QOL) while on long-term oral
sent was obtained from all participants.
anticoagulant therapy has been receiving greater attention
in recent years due to the increase in life expectancy
brought about by advances in medical care. QOL is Data collection and questionnaires
defined as individual satisfaction or happiness with an Eligible patients were identified from the registry of hos-
aspect of life that is affected by their health either in pital and approached by investigators on the day of their
physical (PF), mental, emotional or social functioning respective clinic visit. Patient demographic and clinical
(SF).7 Treatment with an oral anticoagulant may affect data were obtained from their electronic medical records
patient QOL because it requires a change of lifestyle, and face-to-face interviews.
increased risk of bleeding and does not provide objective For patients on warfarin, their INR readings collected
symptomatic relief. Higher satisfaction with regard to over the past 6 months to 1 year were recorded. Patient
anticoagulant treatment is associated with better treatment INR values were tested using the CoaguChek XS system
adherence and therefore improved QOL.8,9 Treatment (Roche Diagnostics, Mannheim, Germany), a point-of-care
satisfaction is defined as an individual’s rating of impor- device at the clinic. Time in therapeutic range (TTR),
tant attributes of the process and outcomes of his or her which is defined as the duration of time in which the
treatment experience, which involve the interaction of patient’s INR values were within a desired range, was
expectation, preference and satisfaction.10,11 calculated using the Rosendaal method.12 The INR target
To date, published data that compare QOL and treat- range was defined according to American College of Chest
ment satisfaction in patients on long-term warfarin versus Physician guidelines, in which the optimum INR target
DOAC are limited. Therefore, the primary objectives of ranges from 2.0 to 3.0. For those with specific VTE
this study were to compare QOL and treatment satisfaction cases, the INR target range was 2.5–3.5.1,2 The INR in
in patients on long-term warfarin versus DOAC. The sec- the first 6 weeks after the initiation of warfarin was
ondary objectives were to compare hospitalization and excluded from the calculation of TTR. In this study, the
bleeding rates between the two groups. cut-off point for good TTR was set at 60% because of any

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 Dovepress Ng et al

value that <58% does not confer a greater clinical benefit sample t-test or the Mann–Whitney U test. The difference
than dual anti-platelet therapy.13 in QOL and treatment satisfaction between anticoagulant
In assessing QOL and treatment satisfaction, the patients groups with age and treatment duration as covariates was
were instructed to answer the Short Form 12v2 Health analyzed by ANCOVA. A P<0.05 was considered statis-
Survey (SF12v2) and Perception of Anticoagulation tically significant in this study. Statistical Package for the
Treatment Questionnaire 2 (PACT-Q2) questionnaires inde- Social Sciences (SPSS for Windows version 25.0, SPSS
pendently with minimal assistance from the investigators. Inc., Chicago, IL, USA) was used for the statistical
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The patients could choose to answer the original English analysis.

version, validated Malay version or validated Chinese
version.14–16 SF12v2 assesses patient QOL in eight domains, Results
namely PF, role physical, bodily pain, general health percep-
Patient demographics and clinical data
tions, vitality, SF, role emotional and mental health. The
A total of 208 patients were recruited. The demographic
physical component summary (PCS) and mental component
characteristics are shown in Table 1. 52.4% of the patients
summary (MCS) were calculated from the eight domains
were taking warfarin and 47.6% of patients were taking
using the Quality Metric’s Health Outcome™ Scoring
DOAC. The mean TTR was 54.9±24.8%, with only 45.0%
Software 5.0. A higher score corresponds to better health
of patients achieving a good TTR. The warfarin group was
state in patients. PACT-Q2 consists of 20 items divided into
significantly younger (mean age 61.3±15.9 versus 69.1
three domains, namely “B” for convenience, “C” for burden
±12.1 years, P<0.001), and had a significantly longer
For personal use only.

of disease and “D” for treatment and anticoagulation treat-

treatment duration (mean duration 8.5±7.0 versus 3.2±2.0
ment satisfaction.17,18 The convenience score was the sum of
years, P<0.001) compared to the DOAC group. The
all the items that were inverted in domains B and C (each
DOAC group had significantly more assisted funding
item score =6 minus the initial score), while the satisfaction
from the government (44.4% versus 20.2%, P<0.001),
score was the sum of the item scores in domain D. A higher
underlying NVAF (88.9% versus 67.9%, P<0.001) and
score corresponds to greater convenience or satisfaction
polypharmacy (49.5% versus 32.1%, P=0.003) compared
regarding the anticoagulant. For patients receiving DOAC,
to the warfarin group. There was no significant difference
item B5 of PACT-Q2, i.e., “certain food to be avoided while
in the distribution of gender, ethnicity, marital status, edu-
taking anticoagulant,” was replaced by “Is it difficult for you
cation level, diet preference, alcohol intake and comorbid-
to take your tablet during meals, as recommended?” because
ities between the two groups.
DOAC do not interact with food.8,19 Besides, DOAC are
recommended to be taken with food to increase absorption.20
Therefore, the original PACT-Q2 scoring was only used in
QOL
The overall QOL of the warfarin and DOAC groups was
patients receiving warfarin, while a modified version of
not significantly different. There was no significant differ-
scoring was used in patients receiving DOAC.
ence in the score of PCS (45.0±10.2 versus 42.7±9.7,
Hospitalization was recorded when the reason for
P=0.083), MCS (52.7±8.5 versus 52.3±8.1, P=0.665) and
admission was attributed to complications with the antic-
each domain of SF12v2 (P=0.055–0.960) between the
oagulant such as bleeding or recurrent thromboembolism.
warfarin and DOAC groups (Table 2). When adjusted for
Patient bleeding history was defined according to the
age and treatment duration, the scores for PCS (44.3±0.9
International Society on Thrombosis and Haemostasis
versus 43.4±1.0, P=0.502; 45.1±1.0 versus 42.6±1.1,
bleeding scale.21,22
P=0.105), MCS (53.0±0.8 versus 51.9±0.8, P=0.365;
52.5±0.8 versus 52.5±0.9, P=0.982) and each domain of
Analysis
SF12v2 (P=0.122–0.979; P=0.220–0.968) were not signif-
Categorical variables were expressed as percentages,
icantly different between the warfarin and DOAC groups.
while continuous variables were expressed as the mean
± SD or median with interquartile range. For categorical
variables, the difference between anticoagulant groups Treatment satisfaction (convenience
was compared using the chi-squared test or Fisher’s score)
exact test. For continuous variables, the difference The overall convenience score was not significantly dif-
between groups was compared by using independent ferent between the warfarin and DOAC groups (79.8±16.9

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Table 1 Demographic characteristics of patients on oral anticoagulants

Characteristics Anticoagulant type (n, %) P-value

Warfarin 109 (52.4) DOACs 99 (47.6)

Age (mean ± SD) Years 61.3±15.9 69.1±12.1 <0.001

Gender (n, %) Male 55 (50.5) 52 (52.5) 0.766

Female 54 (49.5) 47 (47.5)
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Partner status (n, %) No partner 35 (32.1) 35 (35.4) 0.621

With partner 74 (67.9) 64 (64.6)

Ethnicity (n, %) Malay 39 (35.8) 37 (37.4) 0.078

Chinese 63 (57.8) 45 (45.5)
Indian 5 (4.6) 13 (13.1)
Others 2 (1.8) 4 (4.0)

Education (n, %) None 6 (5.5) 7 (7.1) 0.395

Primary 27 (24.8) 19 (19.2)
Secondary 54 (49.5) 44 (44.4)
College/tertiary 22 (20.2) 29 (29.3)

Occupation (n, %) Unemployed 57 (52.3) 44 (44.4) <0.001

For personal use only.

Government dependent/pensioner 22 (20.2) 44 (44.4)

Private 30 (33.2) 11 (11.1)

Diet (n, %) Non-vegetarian/vegan 105 (96.3) 92 (92.9) 0.274

Vegetarian/vegan 4 (3.7) 7 (7.1)

Alcohol (n, %) No 103 (94.5) 98 (99.0) 0.073

Yes 6 (3.8) 1 (1.0)

Comorbidities (n, %) ≤2 69 (63.3) 53 (53.5) 0.153

>2 40 (36.7) 46 (46.5)

Other drugs (n, %) None 11 (10.1) 1 (1.0) 0.003

<5 63 (57.8) 49 (49.5)
≥5 35 (32.1) 49 (49.5)

Indication for anticoagulation (n, %) NVAF 74 (67.9) 88 (88.9) <0.001

VTE 35 (32.1) 11 (11.1)

Duration of therapy (mean ± SD) Years 8.5±7.0 3.2±2.0 <0.001

TTR (mean ± SD) % 54.9±24.8 – –

Good TTR (n, %) Yes 49 (45.0) – –

No 60 (55.0) –
Reasons:
– Above therapeutic range 3 (5.0)
– Above and below therapeutic range 46 (76.7)
– Below therapeutic range 11 (18.3)
Abbreviations: DOACs, direct oral anticoagulants; NVAF, non-valvular atrial fibrillation; VTE, venous thromboembolism; TTR, time in therapeutic range.

versus 82.7±16.7, P=0.229) (Table 3). After adjustment for In the subgroup analysis, the DOAC group had signifi-
age and treatment duration, the convenience scores of the cantly better convenience scores than the warfarin group on
warfarin and DOAC groups remained not significantly item B5 – difficulties in avoidance of certain food (4.5±0.9
different (80.7±1.6 versus 81.7±1.7, P=0.658; 80.1 versus versus 3.9±1.2, P<0.001) and item B7 – difficulties regard-
1.7 versus 82.3±1.8, P=0.410). ing daily life (4.3±1.0 versus 4.0±1.1, P=0.047). After

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adjustment for age and treatment duration, only the differ-

Abbreviations: QOL, quality of life; DOACs, direct oral anticoagulants; SF12v2, Short Form 12v2 Health Survey; PCS, physical component summary; MCS, mental component summary; PF, physical functioning; RP, role physical; BP,
P-value
ence in item B5 remained significant when comparing the

0.105
0.982

0.551
0.397

0.656
0.318

0.968
0.220
0.222
0.032
Adjusted for duration,a mean ± SD; 95% CI
DOAC group and the warfarin group (4.5±0.1 versus ±3.9
±0.1, P=0.001; 4.5±0.1 versus ±3.9±0.1, P<0.001).

42.6±1.1; 40.5–44.7
52.5±0.9; 50.8–54.2

47.9±1.1; 45.8–50.1
43.0±1.1; 40.6–45.4

48.1±1.1; 45.8–50.3
45.0±1.1; 42.8–47.1

52.5±0.9; 50.8–54.3
46.7±1.1; 44.5–49.8
44.0±1.1; 41.9–46.0
50.1±1.1; 47.8–52.3
DOACs Treatment satisfaction (satisfaction score)
The overall satisfaction score was significantly higher in
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the DOAC group compared to the warfarin group (73.5

±12.8 versus 68.7±11.3, P=0.004) (Table 3). The satisfac-
45.1±1.0; 43.1–47.1
52.5±0.8; 50.8–54.2

48.9±1.0; 46.9–50.9
44.5±1.2; 42.3–46.8

47.3±1.1; 45.2–49.5
46.6±1.1; 44.5–48.7

52.6±0.8; 50.9–54.2
48.7±1.1; 46.6–50.8
45.9±1.0; 43.9–47.8
53.7±1.1; 51.5–55.8
tion score remained significantly higher in the DOAC
group compared to the warfarin group after adjusting for
age (73.7±1.2 versus 68.5±1.2, P=0.004) and treatment
Warfarin

duration (73.2±1.3 versus 69.0±1.2, P=0.026).

In the subgroup analysis, the satisfaction score of the
DOAC group was higher than that of the warfarin group
P-value

for each item except item D2 – decrease in symptoms. A

0.502
0.365

0.621
0.963

0.979
0.518

0.308
0.500
0.200
0.122

significantly higher satisfaction score was recorded for

item D3 – experience with side effects (4.1±1.1 versus
For personal use only.

Adjusted for age,a mean ± SD; 95% CI

43.4±1.0; 41.5–45.4
51.9±0.8; 50.3–53.6

48.1±1.0; 46.1–50.1
43.8±1.1; 41.6–46.0

47.7±1.1; 45.5–49.8
45.3±1.1; 43.3–47.4

51.9±0.8; 50.3–53.5
47.2±1.1; 45.1–49.3
44.0±1.0; 42.0–46.0
50.7±1.1; 48.6–52.9

3.4±0.8, P<0.001), which remained significantly higher

even after adjusting for age (4.0±0.1 versus 3.5±0.1,
P<0.001) and treatment duration (4.0±0.1 versus 3.5±0.1,
DOACs

P=0.001). The DOAC group also recorded significantly a

higher satisfaction score for item D6 – satisfaction with
treatment form (4.3±0.7 versus 4.1±0.5, P=0.022), but the
44.3±0.9; 42.5–46.2
53.0±0.8; 51.4–54.6

48.8±1.0; 46.9–50.7
43.9±1.1; 41.7–46.0

47.7±1.0; 45.7–49.7
46.3±1.0; 44.3–48.3

53.1±0.8; 51.6–54.6
48.2±1.0; 46.2–50.2
45.8±1.0; 44.0–47.8
53.1±1.0; 51.0–55.1

bodily pain; GH, general health perceptions; V, vitality; SF, social functioning; RE, role emotional; MH, mental health.

difference was not significant after adjusting for age

(P=0.067) and treatment duration (P=0.052). Finally, the
Warfarin

score for item D7 – overall satisfaction was significantly

higher in the DOAC group than in the warfarin group after
adjusting for age (4.2±0.1 versus 4.0±0.1, P=0.041).
P-value

0.095

0.280
0.731
0.316

0.960
0.209

0.872
0.432
0.076
0.055

Hospitalization and complications

Table 2 Comparison of QOL score between anticoagulant groups

The hospitalization rate was significantly higher in the warfarin

Without adjustment, mean ± SD; 95% CI

43.0±11.0; 40.8–45.2

47.7±10.5; 45.6–49.8
44.9±10.3; 42.8–46.9
47.2±11.2; 44.9–49.4

50.5±10.0; 48.5–52.5
47.6±10.8; 45.5–49.8

group than in the DOAC group (15.6% versus 3.0%, P=0.002)

42.7±9.7; 40.8–44.6
52.3±8.1; 50.7–53.9

52.4±8.3; 50.8–54.1
43.7±9.0; 41.9–45.5

(Table 4). The main reason for hospitalization in the warfarin

group was bleeding (70.6%), while the main reason in the
DOACs

DOAC group was recurrent thrombosis (66.7%). However,

there were no significant differences in the complications of
anticoagulants such as overall bleeding events (24.8% versus
45.0±10.2; 43.1–46.9

44.6±11.6; 42.4–46.8

47.6±10.7; 45.6–49.7
46.7±10.5; 44.7–48.7

46.1±10.5; 44.1–48.1
53.3±11.1; 51.2–55.4
52.7±8.5; 51.1–54.3

52.6±8.1; 51.1–54.2
48.3±9.5; 46.5–50.1

49.1±9.2; 47.4–50.9

20.2%, P=0.431) or thromboembolism events (5.5% versus

3.0%, P=0.381). Among 47 patients with bleeding events, the
Note: Adjusted with ANCOVA test.

clinically relevant minor bleeds and severe bleeding events

Warfarin

were non-significantly higher in the warfarin group than in

the DOAC group (66.7% versus 40.0%, P=0.069).

Discussion
parameters
SF12 v2

In this cross-sectional study, patients who received DOAC

a
MCS

were significantly more satisfied with their treatment, but

PCS

MH
GH
RP

RE
BP
PF

SF
V

there was no difference in QOL or overall convenience

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Table 3 Comparison of convenience and satisfaction score between anticoagulant groups
Ng et al

PACT–Q2 parameters Without adjustment, mean ± SD; 95% CI With age adjustment,a mean ± SD; 95% CI With duration adjustment,a mean ± SD; 95% CI

Warfarin DOAC P-value Warfarin DOAC P-value Warfarin DOAC P-value

DovePress
Convenience score 79.8±16.9; 82.7±16.7; 0.229 80.7±1.6; 81.7±1.7; 0.658 80.1±1.7; 82.3±1.8; 0.410
76.6–83.0 79.3–86.0 77.5–83.9 78.4–85.1 76.8–83.5 78.8–85.9

Convenience item score:

B1. Difficulties in taking the 4.6±0.8; 4.4–4.7 4.5±1.0; 4.3–4.7 0.670 4.6±0.1; 4.4–4.9 4.5±0.1; 4.3–4.6 0.243 4.6±0.1; 4.4–4.7 4.5±0.1; 4.3–4.7 0.806
treatment

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B2. Bother in taking the 4.5±0.8; 4.3–4.7 4.4±1.1; 4.2–4.6 0.455 4.6±0.1; 4.4–4.7 4.3±0.1; 4.2–4.5 0.106 4.5±0.1; 4.3–4.7 4.4±0.1; 4.2–4.6 0.595
treatment

B3. Difficulties regarding dose 4.2±1.1; 4.0–4.4 4.5±1.0; 4.3–4.7 0.081 4.3±0.1; 4.1–4.5 4.4±0.1; 4.2–4.6 0.335 4.2±0.1; 4.0–4.4 4.4±0.1; 4.2–4.6 0.206
adjustment if needed

B4. Difficulties with other 4.4±1.0; 4.2–4.6 4.4±1.0; 4.2–4.6 0.899 4.4±0.1; 4.2–4.6 4.3±0.1; 4.1–4.5 0.439 4.4±0.1; 4.2–4.6 4.4±0.1; 4.2–4.6 0.979
medication during treatment

B5. Difficulties in avoidance of 3.9±1.2; 3.6–4.1 4.5±0.9; 4.3–4.7 <0.001 3.9±0.1; 3.7–4.1 4.5±0.1; 4.3–4.7 0.001 3.9±0.1; 3.7–4.1 4.5±0.1; 4.3–4.8 <0.001
certain food/difficult to take
tablet during meals#

B6. Difficulties taking treatment 4.5±0.9; 4.3–4.6 4.6±0.7; 4.5–4.8 0.120 4.5±0.1; 4.3–4.6 4.6±0.1; 4.5–4.8 0.265 4.5±0.1; 4.3–4.7 4.6±0.1; 4.4–4.8 0.308
while being away from home

B7. Difficulties regarding daily life 4.0±1.1; 3.8–4.2 4.3±1.0; 4.1–4.5 0.047 4.0±0.1; 3.8–4.2 4.2±0.1; 4.0–4.5 0.110 4.0±0.1; 3.8–4.2 4.3±0.1; 4.0–4.5 0.100

B8. Bother in follow–up required 3.9±1.2; 3.7–4.1 4.2±1.0; 4.0–4.2 0.052 4.0±0.1; 3.7–4.2 4.2±0.1; 4.0–4.4 0.163 4.0±0.1; 3.7–4.2 4.2±0.1; 3.9–4.4 0.183

B9. Difficulties in regular intake 4.4±0.9; 4.2–4.5 4.6±0.8; 4.4–4.7 0.073 4.4±0.1; 4.3–4.6 4.5±0.1; 4.3–4.7 0.476 4.4±0.1; 4.2–4.5 4.6±0.1; 4.4–4.8 0.120

B10. Feeling loss of independency 4.4±1.1; 4.2–4.6 4.0±1.3; 3.8–4.3 0.049 4.3±0.1; 4.1–4.6 4.1±0.1; 3.8–4.3 0.127 4.3±0.1; 4.1–4.6 4.1±0.1; 3.8–4.3 0.168

B11. Worried about having to 3.3±1.3; 3.1–3.6 3.2±1.4; 3 2.9–3.4 0.400 3.3±0.1; 3.1–3.6 3.2±0.1; 2.9–3.4 0.326 3.4±0.1; 3.1–3.6 3.1±0.1; 2.9–3.4 0.315
interrupt or stop treatment

C1. Impact of side effects on 4.2±1.0; 4.0–4.4 4.3±1.1; 4.1–4.5 0.630 4.2±0.1; 4.0–4.4 4.2±0.1; 4.0–4.4 0.930 4.3±0.1; 4.1–4.5 4.2±0.1; 4.0–4.4 0.625
usual activities

C2. Discomfort due to symptoms 4.4±0.9; 4.2–4.5 4.5±1.0; 4.3–4.7 0.323 4.4±0.1; 4.2–4.6 4.5±0.1; 4.3–4.7 0.431 4.4±0.1; 4.2–4.6 4.5±0.1; 4.3–4.7 0.520

(Continued)

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Table 3 (Continued).

PACT–Q2 parameters Without adjustment, mean ± SD; 95% CI With age adjustment,a mean ± SD; 95% CI With duration adjustment,a mean ± SD; 95% CI

Patient Preference and Adherence 2019:13

Warfarin DOAC P-value Warfarin DOAC P-value Warfarin DOAC P-value

Anticoagulant treatment 68.7±11.3; 76.6–83.0 73.5±12.8; 0.004 68.5±1.2; 73.7±1.2; 0.004 69.0±1.2; 73.2±1.3; 0.026
satisfaction score 70.9–76.0 66.2–70.8 71.2–76.1 66.5–71.4 70.6–75.7

Satisfaction item score

D1. Feeling of reassurance 3.8±1.1; 3.6–4.0 4.0±1.0; 3.8–4.2 0.150 3.7±0.1; 3.5–3.9 4.0±0.1; 3.8–4.2 0.124 3.7±0.1; 3.5–3.9 4.0±0.1; 3.8–4.2 0.112

D2. Symptom decrease 3.2±1.2; 2.9–3.4 3.2±1.3; 3.0–3.5 0.706 3.1±0.1; 2.9–3.4 3.3±0.1; 3.0–3.5 0.495 3.2±0.1; 3.0–3.5 3.2±0.1; 2.9–3.4 0.828

D3. Experience with side effects 3.4±0.8; 3.3–3.6 4.1±1.1; 3.8–4.3 <0.001 3.5±0.1; 3.3–3.7 4.0±0.1; 3.8–4.2 <0.001 3.5±0.1; 3.3–3.7 4.0±0.1; 3.8–4.2 0.001

D4. Satisfaction regarding 3.8±0.8; 3.6–3.9 3.9±0.9; 3.7–4.1 0.312 3.8±0.1; 3.6–3.9 3.9±0.1; 3.8–4.1 0.126 3.8±0.1; 3.6–4.0 3.9±0.1; 3.7–4.1 0.397
independency

D5. Satisfaction with patient 3.9±0.7; 3.8–4.1 4.0±0.7; 3.9–4.1 0.633 3.9±0.1; 3.8–4.1 4.0±0.1; 3.9–4.1 0.602 3.9±0.1; 3.8–4.1 4.0±0.1; 3.8–4.1 0.690
management

D6. Satisfaction with treatment 4.1±0.5; 4.0–4.1 4.3±0.7; 4.2–4.4 0.022 4.1±0.1; 4.0–4.2 4.3±0.1; 4.1–4.4 0.067 4.1±0.1; 4.0–4.2 4.3±0.1; 4.2–4.4 0.052
form

D7. Overall satisfaction 4.0±0.5; 3.9–4.1 4.2±0.6; 4.0–4.3 0.051 4.0±0.1; 3.9–4.1 4.2±0.1; 4.1–4.3 0.041 4.0±0.1; 3.9–4.1 4.2±0.1; 4.0–4.3 0.120
Notes: aAdjusted with ANCOVA test. The items in domain B and C were expressed as 6 minus item score. The PACT-Q questionnaire was modified for the DOAC group. #Item B5 for DOAC group was amended to “Is it difficult for
you to take your tablet during meals, as recommended?” (this was not validated). Parameters used with permission and adapted from Prins MH, Marrel A, Carita P, et al. Multinational development of a questionnaire assessing patient
satisfaction with anticoagulant treatment: the ‘Perception of Anticoagulant Treatment Questionnaire’ (PACT-Q). Health Qual Life Outcomes. 2009;7:9.17 PACT-Q © 2007 Sanofi-Aventis, France. All rights reserved.
Abbreviations: DOACs, direct oral anticoagulants; PACT-Q2, Perception of Anticoagulation Treatment Questionnaire 2.

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when compared to those receiving warfarin. The sub-ana- complications. The majority of patients in this study who
lysis of the satisfaction domain demonstrated that patients failed to achieve a good TTR had INR above the therapeutic
receiving DOAC were more satisfied with the drug’s side range, which could be a risk for bleeding events.
effects as they were significantly less severe than what Monz et al reported the only QOL comparison for
they expected. This was supported by the finding of a long-term warfarin versus DOAC in a clinical trial, in
significantly lower hospitalization rate as well as fewer which there was no significant difference in the
clinically relevant minor bleeds and severe bleeding events EuroQOL Instrument (EQ-5D) of AF patients in the
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among this group in this study. Additionally, patients Randomized Evaluation of Long-term Anticoagulant
receiving DOAC were more confident in their treatment, Therapy (RELY) sub-study.23 Similarly, Benzimra et al,
as well as more satisfied with the drug form and their Contreras et al and Alegret et al reported no significant
clinical follow-up. This could be due to the advantages differences in QOL between AF patients receiving long-
of DOAC as a newer generation of oral anticoagulant, with term warfarin or DOAC.19,24,25 QOL was assessed by
simpler dosing the absence of frequent blood monitoring, EuroQOL Instrument 3 levels (EQ-5D-3L) in the former
therefore fewer blood tests and clinic visits. Despite no two studies, while the Sawicki questionnaire was used in
difference in the total convenience score, patients receiv- the latter study. Recently, Keita et al reported the only real-
ing DOAC also reported significantly more convenience in life comparison of QOL between patients receiving long-
their food intake compared to those receiving warfarin. term warfarin versus DOAC in VTE, which failed to show
a significant difference in the EQ-5D.8 Several studies
For personal use only.

DOAC should be taken with food, while warfarin requires

control on a high vitamin K diet. Patients receiving DOAC have shown that patients on warfarin required at least 3
and warfarin did not report significantly different QOL months to adapt to their treatment.23,25–27 Their limitations
because anticoagulants neither provide objective sympto- during the initial period may include a higher number of
matic relief nor decrease symptoms. Moreover, QOL clinic visits, frequent blood tests, abrupt diet modifications
assessed beyond 6 months of treatment initiation allowed and difficulty in achieving the expected INR. More than 6
the patients to adapt to their respective treatments. months after treatment initiation, patients should have
Another important finding highlighted in this study was adapted to the anticoagulant treatment, which may explain
that patients receiving warfarin appeared to have more the lack of difference in QOL between the oral anticoagu-
clinically relevant minor bleeds and severe bleeding events. lants in these studies. Another real-life study by Balci et al,
The lack of statistical significance could be due to the small however, reported a significantly better QOL assessed by
number of patients who suffered from bleeding Short Form-36 (SF36), a lower Hospital Anxiety

Table 4 Hospitalization, bleeding and systemic embolism between anticoagulant groups

Characteristics Anticoagulant type (n, %) P-value

Warfarin DOACs
109 (52.4) 99 (47.6)

Hospitalization (n, %) No 92 (84.4) 96 (97.0) 0.002

Yes 17 (15.6) 3 (3.0)

Bleeding 12 (70.6) 1 (33.3)
Thrombosis 5 (29.4) 2 (66.7)

Bleeding severity (n, %) No 82 (75.2) 79 (79.8) 0.270

Minor 9 (8.3) 12 (12.1)

Non-major, clinically relevant 15 (13.8) 7 (7.1)

Major 3 (2.8) 1 (1.0)

Systemic embolism (n, %) No 103 (94.5) 96 (97.0) 0.381

Yes 6 (5.6) 3 (3.0)

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 Dovepress Ng et al

Depression scale score, a lower hospitalization rate, as This study had several limitations. First, it was per-
well as a lower incidence of any type of bleeding event formed in a single center, thus limiting the generalisability
in AF patients receiving long-term DOAC compared to of the results. Second, the cross-sectional design might not
warfarin.28 The DOAC group in this study had been pre- be able to perfectly reflect the QOL, as QOL may vary
viously treated with warfarin, which allowed these patients over time. Third, the poor physical condition of some
to compare both anticoagulant therapies and may have led patients may have been a deciding factor in the choice of
to a bias in self-reported QOL. DOAC over warfarin in daily practice. Fourth, the cost of
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Concerning treatment satisfaction, Prins et al reported sig- treatment was not taken into account when treatment bur-
nificantly better satisfaction in a subgroup of patients receiving den and satisfaction were assessed. Fifth, the amended
DOAC versus enoxaparin/warfarin in the EINSTEIN pulmon- item B5 of PACT-Q2 for DOAC group was not validated.
ary embolism trial.29 Treatment satisfaction in this study was Sixth, the comparison of item B5 for diet in the warfarin
assessed by the Anti-Clot Treatment Scale (ACTS) and the group versus pill intake in the DOAC group may not be
Treatment Satisfaction Questionnaire for Medication II. Cano fair. Seventh, the reporting of treatment complications was
et al also reported a significantly better ACTS burden score subject to the recall bias of the patients, but this was
and numerically better ACTS benefit score in patients receiv- minimized by double-checking available medical records.
ing DOAC versus the standard anticoagulant in the XA inhibi- A multi-center randomized double-blind study would be
the best methodology to eliminate these limitations.
tion with rivaroxaban for Long-term and Initial
Anticoagulation in venous thromboembolism (XALIA)
For personal use only.

study.30 In other real-world studies, Willich et al, Keita et al Conclusion

and Benzimra et al reported significantly better satisfaction DOAC is a better option as an oral anticoagulant in
and convenience among patients receiving DOAC versus patients with NVAF or VTE because of greater satisfac-
warfarin for VTE or AF using PACT-Q2.8,19,31 Recently, tion, more convenience in food intake, less frequent hos-
Contreras et al also reported a similar result that favored pitalization, as well as fewer clinically relevant minor
DOAC in their AF patients based on ACTS and the bleeds and severe bleeding events. Furthermore, achieving
Satisfaction Questionnaire.24 In short, significantly better good TTR in patients on warfarin is challenging.
treatment satisfaction among patients receiving long-term
DOAC compared to warfarin has been consistently high- Ethics approval and informed
lighted in existing clinical trials and real-life studies. consent
The present study concludes that DOAC is a better option The UMMC hospital’s ethics committee approved this
for oral anticoagulant therapy in patients with NVAF or VTE study with reference of Medical Ethic Committee
because of greater satisfaction, more convenience regarding Identity Number (MECID); number 2016823-4147.
food intake, less frequent hospitalization, as well as fewer Written informed consent was obtained from all the
clinically relevant minor bleeds and severe bleeding events. study patients.
This information further complements the results of existing
studies, which focused mainly on comparing the efficacy and Abbreviations
side effects of warfarin versus DOAC. AF, atrial fibrillation; VTE, venous thromboembolism;
To our knowledge, this is the first study that compared INR, international normalized ratio; DOAC, direct oral
QOL and treatment satisfaction in Asian patients on long- anticoagulants; QOL, quality of life; UMMC, University
term warfarin versus DOAC treatment. Patients who Malaya Medical Centre; NVAF, non-valvular atrial fibrilla-
crossed over from warfarin to DOAC or vice versa were tion; TTR, time in therapeutic range; SF12v2, Short
excluded in this study to minimize the reporting bias. The Form 12v2 Health Survey; PACT-Q2, Perception of
analyses of QOL and treatment satisfaction were adjusted Anticoagulation Treatment Questionnaire 2; PF, physical
for age and treatment duration, which has been highlighted functioning; RP, role physical; BP, bodily pain; GH, general
in other studies as important confounding factors.32–34 health perceptions; V, vitality; SF, social functioning; RE,
Each domain of SF12 and each item of PACT-Q2 were role emotional; MH, mental health; PCS, physical compo-
also analyzed and reported in order to provide a more nent summary; MCS, mental component summary; EQ-5D,
detailed comparison. EuroQOL instrument; RELY, Randomized Evaluation of

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 Ng et al Dovepress

Long-term Anticoagulant Therapy; EQ-5D-3L, EuroQOL 9. Wang Y, Kong MC, Lee LH, Ng HJ, Ko Y. Knowledge, satisfac-
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Acknowledgments
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formulation based on review of the literature. Med Care Res Rev.

We want to express our gratitude to all the patients who 1996;53(1):3–27. doi:10.1177/107755879605300101
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the following ways: substantial contributions to conception survey was a valid instrument in Chinese adolescents. J Clin
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The authors report no conflicts of interest in this work.
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