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International Journal of ClinicalPharmacyInternational Journal of ClinicalPharmacy and Pharmaceutical Care ISSN 2210-7703 Int J Clin PharmDOI 10.1007/s11096-013-9796-6

Comparing effectiveness of twoanticoagulation management models in aMalaysian tertiary hospital

Subramaniam Thanimalai, Asrul AkmalShafie, Mohamed Azmi Hassali &Jeyaindran Sinnadurai

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RESEARCH ARTICLE

Comparing effectiveness of two anticoagulation managementmodels in a Malaysian tertiary hospital

Subramaniam Thanimalai • Asrul Akmal Shafie •

Mohamed Azmi Hassali • Jeyaindran Sinnadurai

Received: 21 October 2012 / Accepted: 12 May 2013

� Springer Science+Business Media Dordrecht 2013

Abstract Backgrounds Limited evidence is available

regarding pharmacist managed anticoagulation clinic in the

Southeast Asian region where there is marked difference in

terms of care model, genetic composition and patient

demographics. Objectives This study aimed at comparing

the anticoagulation clinic managed by the pharmacist with

physician advisory and the usual medical care provided in

Kuala Lumpur Hospital (KLH) in terms of anticoagulation

control and adverse outcomes. Setting A 2,302 bedded

government tertiary referral hospital in Malaysia. Methods

A 6-month retrospective cohort study of the effectiveness

of two models of anticoagulation care, the pharmacist

managed anticoagulation clinic which is known as warfarin

medication therapy adherence clinic (WMTAC) and usual

medical clinic (UMC) in KLH was conducted, where a

random number generator was used to recruit patients.

The UMC patients received standard medical care where

they are managed by rotational medical officers in the

physicians’ clinic. As for the WMTAC with physician

advisory, the pharmacist will counsel and review the

patients internationalised normalization ratio at each clinic

visit and also adjust the patients’ warfarin dose accord-

ingly. Patients are referred to physicians if immediate

attention is required. Main outcome measure The main

therapeutic outcome is time in therapeutic range (TTR)

both actual and expanded TTR and thromboembolic and

bleeding complications. Results Each of the WMTAC and

usual medical care recruited 92 patients, which totals to

184 patients. The patient demographics in terms of age,

race and indication of treatment were comparable. At the

end of the 6 months follow-up, patients in the WMTAC

group had significantly higher actual-TTR (65.1 vs.

48.3 %; p \ 0.05) compared to those in usual medical care

group. Rates of admission were 6.5 versus 28.2 events per

100 person-years for the WMTAC and UMC groups,

respectively. Though the bleeding incidences were not

significantly different, it was reduced. Conclusions These

findings will impact local warfarin patient management

services and policies because there was no available evi-

dence supporting the role of pharmacists in the manage-

ment of warfarin patients prior to this study.

Keywords Anticoagulation clinic � Malaysia �Pharmacists � Therapeutic range � Warfarin

Impacts on practice

– Pharmacists in Malaysia can have a clear role in the

management of warfarin therapy in a chronic care

clinic.

– The assistance of pharmacists in managing warfarin

therapy in a clinic in Malaysia improves adherence and

is cost effective.

S. Thanimalai (&)

Kuala Lumpur Hospital, Jln. Pahang, 50586 Kuala Lumpur,

Malaysia

e-mail: subro6@gmail.com

S. Thanimalai

Discipline of Social and Administrative Pharmacy,

School of Pharmaceutical Sciences, Universiti Sains Malaysia,

11800 George Town, Penang, Malaysia

A. A. Shafie � M. A. Hassali

School of Pharmaceutical Sciences, Universiti Sains Malaysia,

11800 George Town, Penang, Malaysia

J. Sinnadurai

Department of General Medicine, Kuala Lumpur Hospital,

Jln. Pahang, 50586 Kuala Lumpur, Malaysia

123

Int J Clin Pharm

DOI 10.1007/s11096-013-9796-6

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Introduction

Warfarin has become the most widely used oral anticoag-

ulant since its introduction in 1954. Due to its pharmaco-

kinetic and pharmacodynamic complexities, the

management of warfarin therapy to obtain an optimal

outcome is a great challenge. Inadequate doses lead to

thromboembolic events, while patients that receive exces-

sive anticoagulation are at risk of bleeding [1, 2]. Multiple

factors have been shown to affect anticoagulation control,

such as warfarin dosage, warfarin dosage preparation, drug

or food interactions, patient compliance, patient knowledge

and the setting of anticoagulation services [3].

The effective management of warfarin therapy requires

a considerable amount of clinician time and resources

because of the need for frequent International Normaliza-

tion Ratio (INR) laboratory tests and dosing adjustments

[4]. Thus, various approaches have been recommended to

improve anticoagulant care. These approaches include

anticoagulation monitoring services, point-of-care testing,

computer decision support systems and patient self-man-

agement [5]. Studies have shown that an anticoagulation

management service that is administered by a pharmacist is

one of the most effective methods for the management of

anticoagulation [6, 7]. Additionally, a meta-analysis has

demonstrated that anticoagulation management services

have improved care, in terms of anticoagulation control,

and reduced thromboembolic and hemorrhagic events. In a

random-effect meta-analysis of randomized controlled tri-

als (RCTs), the group that received pharmacist-supported

warfarin therapy had statistically significant improvements

in the prevention of total bleeding [RR, 0.51; 95 % confi-

dence interval (CI), 0.28–0.94]. However, the effects on

major bleeding (RR, 0.64; 95 % CI, 0.18–2.36), thrombo-

embolic events (RR, 0.79; 95 % CI, 0.33–1.93), mortality

from all causes (RR, 0.93; 95 % CI, 0.41–2.13) and mor-

tality from warfarin-related causes (RR, 0.65; 95 % CI,

0.18–2.42) were not significant [3]. Most of these studies

were conducted in North America or Europe [8, 9]. While

some Asian-based studies are now available, there are

major variations in terms of the healthcare management

system [9–12], and inter-country variations include reim-

bursement policies, prescribing patterns, traditions, opinion

leaders with conflicts of interests, domestic pharmaceutical

production and clinical practice guidelines [13].

The usual medical clinic (UMC) service that is used for

the management of warfarinized patients in Malaysian

government health facilities is a clinic that is run by rota-

tional medical officers and physicians. Patients are seen on

an appointment basis for their follow-up.

To offer comprehensive and focused patient care, the

Pharmaceutical Service Division of the Ministry of Health

Malaysia has initiated the Medication Therapy Adherence

Clinic (MTAC) as part of their ambulatory pharmacy ser-

vices. The pharmacist-managed anticoagulation clinic, or

the Warfarin MTAC (WMTAC), was initiated in Malaysia

in 2005 [14].

Aim of the study

The WMTAC is being introduced in a step-wise manner in

Malaysia. Formal assessments of these clinics are needed

to appraise their value prior to nationwide initiation.

Therefore, this study aims to compare the impact of the

WMTAC service with the UMC service that is provided at

a general medical clinic in terms of anticoagulation control.

Methods

The study subjects were patients who had been indicated

for and treated with chronic warfarin therapy. These

patients had been monitored for at least 6 months at the

Department of General Medicine, Kuala Lumpur Hospital

(KLH), which is a 2300-bedded national referral center in

Malaysia.

Anticoagulation management model in KLH

UMC

At the first clinic visit, patients were seen by a medical

officer for history taking and assessment. During this visit,

the patients received a warfarin record book. At subsequent

follow-ups, the warfarin dose was adjusted by the rota-

tional medical officers according to the patients’ INR. If

there was a marked derangement of the INR, a brief

counseling session was provided by the medical officers.

The patients were also referred to the physician on call for

further review if necessary.

WMTAC

The WMTAC is managed by pharmacists with support

from physicians. A management protocol that was

approved by the Pharmaceutical Services Division, Min-

istry of Health Malaysia, was adopted following discus-

sions between the Head of the Medical Department and the

pharmacists that were involved in the WMTAC. Upon

referral to the WMTAC, all new patients were informed of

the role of the WMTAC in the patients’ anticoagulation

care. The pharmacist then collected a detailed patient his-

tory pertaining to anticoagulation therapy before providing

each patient with an individualized educational session and

an information package. The information package

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consisted of a patient education guidebook on warfarin

therapy and a warfarin consumption record sheet spanning

12 months. The education session was conducted accord-

ing to a standard in-house counseling checklist that was

developed by the WMTAC pharmacists. The patients were

counseled on the importance of communicating any chan-

ges in their general health, medications or lifestyle. The

risks and benefits of warfarin, the factors that affect its

efficacy and an awareness of the signs and symptoms of

hemorrhagic and thromboembolic complications were also

addressed. The patients who returned for their subsequent

monitoring appointments were assessed by the pharmacist

according to their INRs and to a standard question list that

was developed by the WMTAC pharmacists. The infor-

mation was then documented and used to determine the

most appropriate warfarin dose and the date of the next

monitoring appointment. Standard questions were used to

assess patient compliance and changes in the patients’

medication, food or lifestyle and to identify adverse drug

events. Another pharmacist in the WMTAC counter-

checked the doses and appointment dates before providing

the patients with their warfarin supply. The patients were

only referred to the physician on call if needed or in cases

of emergencies, as stated in the management protocol [15].

The on-call physician reviewed the prescriptions at the end

of the clinic day, and a discussion was initiated with the

pharmacist if needed. As part of continuous quality assur-

ance, the WMTAC pharmacists also held regular case

discussions to address specific patients or issues that were

in need of attention at the end of the clinic day.

A six-month retrospective cohort study was conducted

to compare the effectiveness of the two anticoagulation

care models, the WMTAC and the UMC. The study design

is illustrated in Table 1. The data for the UMC were col-

lected between January 2008 and January 2011. The

WMTAC was established in the hospital in 2008 and

operated concurrently with the UMC. Data from between

January 2009 and January 2012 were used for the WMTAC

group. Both groups were followed for 6 months from the

initiation of their warfarin therapy.

A web-based random number generator (http://www.

randomizer.org/) was used to generate identifiers for the

patients that were included in this study. These patients

were selected from the list of patients that were enrolled in

both the UMC and the WMTAC. Warfarinized patients

were included if their age was above 18 years and if they

had been managed for at least 6 months in either one of the

clinics. The exclusion criteria that were used were as fol-

lows: patients were excluded if their warfarin indication

was due to anti-phospholipid syndrome, if they were

managed for less than 6 months in one of the care models

or if their medical records were inaccessible due to death or

relocation.

The primary outcome measure was the control of the

INR over 6 months, per proportion of the time within both

the therapeutic (TTR) range and the expanded therapeutic

INR range in the management protocol. The therapeutic

INR ranges for anticoagulation are 2.0–3.0 for prophylaxis

and for the treatment of uncomplicated disease and 2.5–3.5

for patients with mechanical heart valves or for failure with

previous warfarin treatment. These ranges are in accor-

dance with the recommendations of the American College

of Chest Physicians Consensus Conference on Antithrom-

botic Therapy [16]. The therapeutic INR range was

expressed in terms of the proportion of time that the INR

values of the individuals were within the target/therapeutic

INR range. Being at risk for thromboembolic or bleeding

was the outcome that was used as the effectiveness mea-

surement [17]. The expanded therapeutic INR range was

defined as the therapeutic range ±0.2 INR units [11, 18].

This expanded range is not considered clinically important

and would not necessarily require a dosage adjustment

[18]. As described by Rosendaal et al., the percentage of

time that the patients were within the therapeutic and

expanded therapeutic INR ranges was estimated using

linear interpolation between the measured INR values [19].

This method allowed the determination of the optimal

effects of anticoagulation [19] and took into account the

actual number of days in the target range. This method also

enabled the calculation of the INR-specific incidence rates

of adverse events [16].

The secondary outcome measurement that was used was

the combined occurrence of adverse events, including both

thromboembolic and hemorrhagic events. The classifica-

tion criteria for thromboembolic events (TE) were pre-

specified as follows: the severity was categorized as life

threatening if it involved irreversible damage that required

an emergency procedure or admission to an intensive care

unit or as significant if it involved hospitalization or an

emergency visit. The hemorrhagic events were classified

by the site of the bleeding and categorized as life threat-

ening if they resulted in a serious permanent injury or

required surgical or angiographic intervention or as

potentially life threatening if they were associated with 2 of

the following conditions: severe blood loss, hypotension,

which is defined by a C20 mmHg drop in systolic blood

pressure to B90 mmHg, or the requirement of hospital-

ization or an emergency visit. The guidelines suggest a

minimum of 4 weeks between INR assessments for stable

patients [20], with programs often allowing for a maximum

time of 6 weeks between INR assessments [21]. Travelling

costs that are incurred due to monthly clinic visits, which

are often required in cases of unstable INR control, are

known to be burdensome to patients [22]. Thus, in addition

to the above outcomes, the average number of clinic visits

was also measured.

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The sample size that is needed to detect a clinical dif-

ference was calculated as follows: the pharmacist-managed

clinic should increase the percent of time in the therapeutic

range from 50 %, which is usually observed in the physi-

cian-managed clinic, to 60 % [18]. A sample size of

approximately 120 patients per group would be needed for

a standard deviation of 0.25 between the groups and for a

statistical power of 80 % with an a error of 5 % to detect

the difference. To allow for the possibility of incomplete

data collection from some patients, a sample size of 150

patients, 20 % more than the predetermined 120 patients,

was selected.

The researcher screened the patients’ warfarin record

books, clinic files and admission records. The data col-

lection included patient demographics and the target INR

range, as predetermined during warfarin initiation. The

following anticoagulation-related information was also

collected for both groups: the INR values, all episodes that

were related to bleeding or thrombosis and other antico-

agulation-related issues that caused an immediate visit to

the clinic, emergency department or hospitalization. For

the UMC patients, emergency department visits and hos-

pital admission information were assessed by reviewing the

warfarin record books and clinic or in-patient medical

records. For the WMTAC patients, emergency department

visits and hospital admission information were obtained

from the WMTAC files. The clinic or in-patient medical

records were assessed if the information was insufficient.

Additional clinic visits or hospitalizations that were due to

warfarin-related adverse drug events were also recorded.

Statistical analysis was performed using SPSS for

Windows 11.5 (SPSS Inc., Chicago, IL, USA). The data are

presented as the mean and standard deviation (SD). The

patient demographics, the percentage of patients within the

therapeutic and expanded therapeutic INR ranges and the

incidence of bleeding and TE between the two groups were

compared using the unpaired Student’s t test or Fisher’s

exact test, as appropriate. A p value of \0.05 was con-

sidered statistically significant.

Results

A total of 184 patients, with 92 patients in each group, were

included in this study. A comparison of the patients’

characteristics is shown in Table 2.

The baseline characteristics of the patients in the UMC

group and the WMTAC group were similar. The demo-

graphic data in terms of age, gender, race and warfarin

indication were not significantly different. The racial dis-

tribution of the patients was in accordance with the

Malaysian population. There was also no significant

Table 1 Anticoagulation management services provided in Kuala Lumpur Hospital (KLH)

Warfarin - Medication Therapy Adherence Clinic

Random Sampling –Random Number Generator

Excluded:

48 patients

Excluded:

71 patients

UMC

92 patients

WMTAC

92 patients

Primary Outcomes Measures

INR control over 6 months (Time within therapeutic (TTR) and expanded therapeutic INR ranges)

Secondary Outcomes Measures

Combined occurrence of adverse events (both thromboembolic and hemorrhagic events)

Usual Medical Clinic –Warfarin Clinic

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difference in terms of the smoking status or the alcohol

consumption status. As shown in Table 3, the primary

outcome of the TTR was significantly increased in the

WMTAC patients compared with that in the UMC patients

(66.1 vs. 48.3 %; p \ 0.001). The significantly longer TTR

that was observed in the WMTAC group was maintained

even when the expanded therapeutic range was used (79.3

vs. 65.1; p \ 0.001).

The number of admissions was significantly higher

(p = 0.016) among the UMC patients than among the

WMTAC patients. The rates of admission were 6.5 and

28.2 events per 100 person-years for the WMTAC group

and the UMC group, respectively. There were 13 UMC

patient admissions that were due to over-anticoagulation,

and one patient was admitted for suspected thromboem-

bolism. Of the 10 patients that were admitted for over-

anticoagulation, none were classified as life threatening, 1

was classified as potentially life threatening, and the rest

were classified as significant hemorrhagic events. The

admission for probable thromboembolism was classified as

a significant thromboembolic event. Among the over-an-

ticoagulated patients, 2 were admitted for bruises, 2 for

vaginal bleeding, 2 for gum bleeding, 1 for blood in the

urine and 1 for blood in the stool. More than 2 bleeding

sites, such as blood in the urine and vaginal bleeding, were

observed in 2 patients. In the UMC group, another 2

patients were admitted for observation. All 3 WMTAC

patients who were admitted were admitted for over-anti-

coagulation. None of the admitted patients were classified

as life threatening. One patient was classified as potentially

life threatening, and the other 2 were classified as signifi-

cant. One patient had both vaginal and urinary tract

bleeding, 1 patient had bruises, and the other had gum

bleeding. In the WMTAC patients, the incidence of both

major and minor bleeding was lower than that in the UMC

patients; however, this difference was not statistically

significant (p = 1.000 for both).

The average number of clinic visits was significantly

lower for the WMTAC patients (7.9 ± 2.4) than for the

UMC patients (11.2 ± 3.1) (p \ 0.05).

Discussion

The pharmacist-managed anticoagulation clinic, the

WMTAC, has been shown to provide significantly better

anticoagulation control. The individual assessment of the

patients’ INRs and the relevant factors that contribute to

changes in the INRs, if any, by the pharmacist enables the

adjustment of the appropriate dosage. The use of a treatment

protocol also ensures the uniformity and appropriateness of

the treatment. In our study, the introduction of the WMTAC

also led to a reduction in bleeding-related admissions and to a

Table 2 Characteristics of patients from both usual medical clinic

(UMC) and pharmacist managed anticoagulation clinic (WMTAC)

Characteristics UMC

(n = 92)

WMTAC

(n = 92)

p Value

Age, mean (SD) 64.1 (11.9) 63.2 (13.0) 0.600

Gender, n (%) 0.700

Male 48 (52.2) 46 (50)

Female 44 (47.) 46 (50)

Race, n (%) 0.130

Malay 50 (54.3) 53 (57.6)

Chinese 28 (30.4) 33 (35.9)

Indian 13 (14.1) 4 (4.3)

Others 1 (1.1) 2 (2.2)

Warfarin indications, n (%) 0.152

Atrial fibrillation (AF) 80 (87) 70 (76.1)

Mechanical valve

replacement (MVR)

2.2 (2) 4 (4.3)

Aortic valve replacement

(AVR)

1.1 (1) 0 (0)

Deep vein thrombosis (DVT) 1.1 (1) 6 (6.5)

Others 8.7 (8.9) 12 (13)

Co-morbidity (%) 87 (94.6) 84 (91.3) 0.388

Hypertension 59 (64.1) 61 (66.3)

Diabetes mellitus 35 (38) 26 (28.3)

Dyslipidemia 22 (23.9) 23 (25)

Ischemic heart disease 17 (18.5) 17 (18.5)

Stroke 6 (6.5) 3 (3.3)

Thyroid disorder 6 (6.5) 7 (7.6)

Gastro disorder 1 (1.1) 3 (3.3)

Congestive cardiac failure/

heart failure

8 (8.7) 7 (7.6)

Asthma 4 (4.3) 3 (3.3)

CRHD 3 (3.3) 2 (2.2)

Acute coronary syndrome 4 (4.3) 2 (2.2)

Uric acid disorder 2 (2.2) 3 (3.3)

Chronic kidney disease 1 (1.1) 1 (1.1)

Cardiomyopathy 2 (2.2) 3 (3.3)

Mitral regurgitation 2 (2.2) 1 (1.1)

Others 7 (7.6) 11 (12)

Alcohol consumption (%) 0.109

Non consumer 88 (81) 81.5 (75)

Seldom consumer 4.3 (3) 1.1 (1)

Occasional consumer 3.3 (4) 6.5 (6)

Regular consumer 2.2 (2) 0 (0)

High consumer 1.1 (1) 4.3 (4)

Unknown 1.1 (1) 6.5 (6)

Smoker status (%) 0.08

Non-smoker 85.9 (79) 82.6 (76)

Ex-smoker 5.4 (5) 5.4 (5)

Smoker 8.7 (8) 5.4 (5)

Unknown 0 (0) 6.5 (6)

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significant reduction in the average number of clinic visits.

These findings are similar to those previously published in a

systematic review [9]. A recent study in Canada [23] found

that, even when the clinics managed by physicians and those

managed by pharmacists were of high quality, as defined by a

high TTR of more than 60 %, there was a significant differ-

ence between the clinics. An improvement of at least 5 % in

the TTR is considered clinically significant, and in this study,

the difference was 17.8 %. However, this improvement

should be maintained because the observed TTR was only at

the lower border of the recommended benchmark target for

the TTR, which is 66 %.

No significant difference was observed in the bleeding

events between the groups, and their incidence was similar

to other reported studies [9]. However, no thromboembolic

events were reported, which could be due to the short

6-month follow-up. Thus, the reduction in thromboembolic

events that was identified in a two-year study [24] in 2007

for a pharmacist-managed anticoagulation clinic could not

be confirmed in our study.

The WMTAC was able to provide a more organized and

systematic monitoring of the warfarinized patients because

the pharmacists were able to take time to identify the drug-

related problems and address them. Even with the increase

in the contact time with a health professional, the WMTAC

was able to reduce the overall clinic waiting time by almost

50 % [25]. The WMTAC patients were referred to the

physician 24 times within the 6 months of the study to

increase, withhold or reduce the warfarin dosages or for

further assessment and other complaints. With the

increasing demand for physicians and the shortage of

physician time and availability [26], fewer referrals would

free physicians of the additional burden of the management

of anticoagulated patients.

Pharmacist-managed anticoagulation clinics have been

favored by both physicians and patients [27]. Patients and

society incur costs when travel to a clinic is required. Patient

costs include travelling costs, other out-of-pocket expenses,

the value of lost leisure time and the net wage deduction that

is associated with the clinic visits of employed patients

during work hours [28]. The significantly reduced number of

visits among the WMTAC patients would lead to various

benefits, such as reduced travelling expenses and work time

loss for both patients and their caregivers. In our study, the

collaborative care process at KLH of pharmacist-managed

care with physician support, in which most patients are seen

by the pharmacist and referral to the physician is done per

protocol or on an as-needed basis [15], improved patient care

by addressing drug-related problems and reducing the

number of clinic visits.

The limitations of this study include the study design

and the inability to detect thromboembolic outcomes. The

ideal design for an intervention study is a randomized

controlled trial; however, because this type of trial is

impractical, a retrospective study with controls was used.

Bias was reduced by using a random number generator to

obtain identifiers for the studied population. The inability

to detect thromboembolic outcomes could have been due to

insufficient sample size. However, a systematic review

identified that in all reviewed studies the TTR is signifi-

cantly related to adverse outcomes, including major hem-

orrhagic and thromboembolic events [29]. This result

supports the use of the TTR as the optimal measure of INR

control and clinical outcomes. The systematic review

concluded that a 7 % increase in the TTR would prevent 1

major hemorrhagic event per 100 patient years and that a

12 % increase in the TTR would prevent 1 major throm-

boembolic event per 100 patient years. Although this study

was not able to identify a difference in adverse events,

there were significantly lower admission rates for the

patients in the WMTAC group than in the UMC group.

Similar observations were reported in a recent study in the

United States [30].

Table 3 Clinical outcomes of the usual medical clinic and pharma-

cist managed anticoagulation clinic

Outcomes UMC

(n = 92)

WMTAC

(n = 92)

Mean

difference

(95 % CI)

p Value

Percentage of

time within

therapeutic

range

48.3 ± 24.6 66.1 ± 23.2 16.7 (9.8,

23.7)

\0.001

Percentage of

time within

expanded

therapeutic

range

65.1 ± 18.6 79.3 ± 23 16.0 (9.9,

22.1)

\0.001

Major bleeding

events, n (%)

2 1 [0.05

Minor bleeding

events, n (%)

4 3 [0.05

Admission, n

(%)

13 3 \0.05

Total person-

years of

follow up

46 46

Incidence rate

of major

bleeding

events (%)

4.3 2.2

Incidence rate

of minor

bleeding

events (%)

8.7 6.5

No. of

admission per

100 person

years

28.2 6.5

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The pre-determined sample size was not achieved due to a

temporary change in policy to enroll patients into the

WMTAC after 3 months at the UMC. This change made

patients ineligible to be included in the study because they

have already been treated at the UMC. This temporary

change in policy, which was reverted, interrupted the study;

thus, the intended number of samples could not be attained

within the planned duration of the study recruitment.

Conclusion

This study has shown that the WMTAC resulted in better

anticoagulation care compared with the UMC. These

findings will impact local warfarin patient management

services and policies because there was no available evi-

dence supporting the role of pharmacists in the manage-

ment of warfarin patients prior to this study. Although a

higher cost is expected due the use of pharmacists and the

use of point-of-care testing, future research should evaluate

the cost effectiveness of such services in preventing

adverse events that are associated with warfarin use.

Acknowledgments We would like to acknowledge and thank the

Kuala Lumpur Hospital for granting permission to use the hospital

and its resources to conduct this study. We gratefully acknowledge all

of the hospital staff who contributed to the study and DAWN Clinical

Software for the AC software used to provide the percentage of time

within the therapeutic range calculations.

Funding The research is funded by the University Sains Malaysia,

Research University Grant. The author is sponsored by the Federal

Training Grant, Ministry of Health for post-graduate research.

Conflicts of interest No conflict of interest to declare.

References

1. Pirmohamed M. Warfarin: almost 60 years old and still causing

problems. Br J Clin Pharmacol. 2006;62(5):509–11.

2. Wysowski DK, Nourjah P, Swartz L. Bleeding complications

with warfarin use: a prevalent adverse effect resulting in regu-

latory action. Arch Intern Med. 2007;167(13):1414–9.

3. Saokaew S, Permsuwan U, Chaiyakunapruk N, Nathisuwan S,

Sukonthasarn A. Effectiveness of pharmacist-participated war-

farin therapy management: a systematic review and meta-analy-

sis. J Thromb Haemost. 2010;8(11):2418–27.

4. Sullivan PW, Arant TW, Ellis SL, Ulrich H. The cost effective-

ness of anticoagulation management services for patients with

atrial fibrillation and at high risk of stroke in the US. Pharma-

coeconomics. 2006;24(10):1021–33.

5. Ansell J, Hirsh J, Dalen J, Bussey H, Anderson D, Poller L, et al.

Managing oral anticoagulant therapy. Chest. 2001;119(1 Sup-

pl):22S–38S.

6. Bungard TJ, Gardner L, Archer SL, Hamilton P, Ritchie B,

Tymchak W, et al. Evaluation of a pharmacist-managed antico-

agulation clinic: Improving patient care. Open Med. 2009;3(1):

e16–21.

7. Donovan JL, Drake JA, Whittaker P, Tran MT. Pharmacy-man-

aged anticoagulation: assessment of in-hospital efficacy and

evaluation of financial impact and community acceptance.

J Thromb Thrombolysis. 2006;22(1):23–30.

8. You JH, Chan FW, Wong RS, Cheng G. Cost-effectiveness of

two models of management for patients on chronic warfarin

therapy—a Markov model analysis. Thromb Haemost.

2003;90(6):1106–11.

9. Saokaew S, Sapoo U, Nathisuwan S, Chaiyakunapruk N, Perm-

suwan U. Anticoagulation control of pharmacist-managed col-

laborative care versus usual care in Thailand. Int J Clin Pharm.

2012;34(1):105–12.

10. Choe H, Kim J, Choi K, Mueller B. Implementation of the first

pharmacist-managed ambulatory care anticoagulation clinic in

South Korea. Am J Health-Syst Pharm. 2002;59(9):872–4.

11. Chan FW, Wong RS, Lau WH, Chan TY, Cheng G, You JH.

Management of Chinese patients on warfarin therapy in two

models of anticoagulation service—a prospective randomized

trial. Br J Clin Pharmacol. 2006;62(5):601–9.

12. Kong MC, Ng HJ, Lee PL, Chan YH, Tan D, Lee LH. Imple-

mentation and impact of a hybrid pharmacist-assisted anticoag-

ulation clinic model on the quality of anticoagulation therapy.

Clin Appl Thromb Hemost. 2012;18(3):334–7.

13. Fretheim A, Oxman AD. International variation in prescribing

antihypertensive drugs: its extent and possible explanations.

BMC Health Serv Res. 2005;5(1):21.

14. Government of Malaysia. Pekeliling Perkhidmatan. In: Malaysia

PSDo, editor. Putrajaya; 2007. p. 1–545.

15. Medication Therapy Adherence Clinic. Warfarin. First Edition

2010. Kuala Lumpur: Perpustakaan Negara Malaysia; 2010.

16. Hirsh J, Dalen J, Anderson DR, Poller L, Bussey H, Ansell J,

et al. Oral anticoagulants: mechanism of action, clinical effec-

tiveness, and optimal therapeutic range. Chest. 2001;119(1 Sup-

pl):8S–21S.

17. Fitzmaurice DA, Blann AD, Lip GYH. Bleeding risks of anti-

thrombotic therapy. BMJ. 2002;325(7368):828–31.

18. Wilson SJ-A, Wells PS, Kovacs MJ, Lewis GM, Martin J, Burton

E, et al. Comparing the quality of oral anticoagulant management

by anticoagulation clinics and by family physicians: a random-

ized controlled trial. Can Med Assoc J. 2003;169(4):293–8.

19. Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A

method to determine the optimal intensity of oral anticoagulant

therapy. Thromb Haemost. 1993;69(3):236–9.

20. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G.

Pharmacology and management of the vitamin K antagonists:

American College of chest physicians evidence-based clinical

practice guidelines (8th edition). Chest. 2008;133(6 Suppl):

160S–98S.

21. Chamberlain MA, Sageser NA, Ruiz D. Comparison of antico-

agulation clinic patient outcomes with outcomes from traditional

care in a family medicine clinic. J Am Board Fam Pract.

2001;14(1):16–21.

22. Hwang JM, Clemente J, Sharma KP, Taylor TN, Garwood CL.

Transportation cost of anticoagulation clinic visits in an urban

setting. J Manag Care Pharm. 2011;17(8):635–40.

23. Young S, Bishop L, Twells L, Dillon C, Hawboldt J, O’Shea P.

Comparison of pharmacist managed anticoagulation with usual

medical care in a family medicine clinic. BMC Fam Pract.

2011;12(88):1471–2296.

24. Poon IO, Lal L, Brown EN, Braun UK. The impact of pharma-

cist-managed oral anticoagulation therapy in older veterans.

J Clin Pharm Ther. 2007;32(1):21–9.

25. Thanimalai S CT, Ariffin F, Chan CK, Chan BS, Chong SH,

Heng SY. Achieving INR targets and improving satisfaction of

Warfarinized patients, Kuala Lumpur Hospital. J Quality

Improvement. 2010;2:50–67 [Original Article].

Int J Clin Pharm

123

Author's personal copy

26. Cindy J, Guy L. Enhancing patient care via a pharmacist-man-

aged rural anticoagulation clinic. Healthc Q. 2009;13(Sp):69–74.

27. Lodwick AD, Sajbel TA. Patient and physician satisfaction with a

pharmacist-managed anticoagulation clinic: implications for

managed care organizations. Manag Care. 2000;9(2):47–50.

28. Jowett S, Bryan S, Mahe I, Brieger D, Carlsson J, Kartman B,

et al. A multinational investigation of time and travelling costs in

attending anticoagulation clinics. Value Health. 2008;11(2):

207–12.

29. Wan Y, Heneghan C, Perera R, Roberts N, Hollowell J, Glasziou

P, et al. Anticoagulation control and prediction of adverse events

in patients with atrial fibrillation: a systematic review. Circ

Cardiovasc Quality Outcomes. 2008;1(2):84–91.

30. Rudd KM, Dier JG. Comparison of two different models of

anticoagulation management services with usual medical care.

Pharmacotherapy. 2010;30(4):330–8.

Int J Clin Pharm

123

Author's personal copy