Home' Australian Pharmacist : February 2013 Contents 40 Australian Pharmacist February 2013 I ©Pharmaceutical Society of Australia Ltd.
The majority of the trials had one or more
type of bias such as selective reporting,
selection, attrition and performance bias.
• Databases such as CENTRAL, DARE and
the NHS Health economics database
on The Cochrane Library (2012, Issue
4);MEDLINE (1950 to Apr 2012) and
EMBASE (1974 to Apr 2012) were
searched. The World Health Organization
(WHO) International Clinical Trials
Registry Platform (ICTRP) (http:// apps.
who.int/trialsearch/), the Current
Controlled Trials Register (www.
controlled-trials.com/) and citation
searches and a review of the references of
all full text papers were also performed.
• A total of 12 studies were included in the
review. These were subdivided into four
main clinical groups; 5 mg versus 10 mg;
5 mg versus other doses; age adjusted
warfarin dose; and genotype loading
dose adjusted group.
• The primary outcome measures included
time to first INR in range, time to two
consecutive INRs in range, proportion of
INRs in range from day of initiation and
percentage of time INR is in range.
• The secondary outcome measures
included data on quality of life,
proportion of subtherapeutic INRs,
vitamin K given and adverse effects
within 28 days of warfarin inititiation such
as hospitalisations, blood transfusions,
DVT, PE or other thrombolic events.
• In the 5 mg versus 10 mg loading dose
group, four studies with a total of 355
participants were included. There were
no differences in INR between the 10 mg
and the 5 mg loading dose. All studies
repeated INR to be within the required
range by day 5.
• In the 5 mg versus other doses group,
only two studies with a total of 322
participants were included. 5 mg loading
dose was compared with 2.5 mg and
other calculated doses that took into
account patients' age, weight and serum
albumin. Patients received the calculated
doses achieved a quicker INR range on or
before day 6 than the control group.
• The age adjusted group included 2
studies with a total of 192 patients.
They compared loading doses adjusted
for age versus standardised dosing with
no age adjustments. The results showed
that by day 5, more patients in the age
adjusted group achieved a stable INR
group than the non-age adjusted group.
• In the genotype trials, four studies were
included with a total of 701 participants.
Loading doses were calculated based on
patients genotype compared with 5 mg
and 10 mg loading doses. Three studies
reported no overall differences in INR;
the fourth study, which reported that
the genotype group spent significantly
more time in-range (P < 0.001) and
had a control group whose INRs were
significantly lower than expected.
• No studies reported any data on the
quality of life.
• Vitamin K use was reported more
frequently in the patients taking the
10 mg doses.
• There was insufficient data in the
included studies to report any serious
Implications for research and
The above mentioned review highlights
both the lack of high quality evidence
to guide the appropriate initiation of
warfarin and the heterogeneity of the
outcomes measures reported in the
existent trials. Standardised reporting of
defined outcomes at days three through
to eight and follow up of adverse events
for long period of time up to 30 days after
warfarin initiation is needed to draw firm
There is no current evidence to suggest
a 10 mg loading dose is superior to 5 mg.
In elderly people, lower initiation doses
or age adjusted doses may be more
appropriate, leading to fewer high INRs.
1. Mahtani KR, Heneghan CJ, Nunan D, et al. Optimal loading
dose of warfarin for the initiation of oral anticoagulation.
Cochrane Database of Systematic Reviews 2012, Issue 12. Art.
No.: CD008685. DOI: 10.1002/14651858.CD008685.pub2.
2. Wadelius M, Chen LY, Lindh JD, et al. The largest prospective
warfarin treated cohort supports genetic forecasting. Blood
3. Schulman S, Beyth RJ, Kearon C, Levine MN. Hemorrhagic
complications of anticoagulant and thrombolytic treatment:
American College of Chest Physicians evidence-based
clinical practice guidelines (8th edition). Chest 2008;133(6
4. Darkow T, Vanderplas AM, Lew KH, Kim J, Hauch O. Treatment
patterns and real-world effectiveness of warfarin in nonvalvular
atrial fibrillation within a managed care system. Current
Medical Research and Opinion 2005;21(10):1583--94.
Transition care helps
Almost half of all older people who left
hospital and received assistance through
the Transition Care Program (TCP) returned
to the community in 2010--11, according
to a report released by the Australian
Institute of Health and Welfare (AIHW).
The report, Older people leaving hospital:
a statistical overview of the Transition Care
Program 2009-10 and 2010-11, presents
recent statistics and examines some
TCP has been operating since 2005--06,
and provides short-term care to older
people who would be assessed as
otherwise eligible for at least low-level
residential care as they leave hospital.
It aims to improve clients› independence
and functioning and delay entry into
residential aged care.
The report shows that of the people who
received any care under the program in
2010--11, 56% had improved functioning
during their care and more than 8,400
(49%) returned to the community.
A further 19% of recipients entered
residential care, 23% returned to hospital
and 2% died.
AIHW spokesperson Brent Diverty said:
'The number of people receiving care as
part of the program increased from about
15,000 in 2009--10 to about 18,000 in
'Overall, looking at those who completed
their planned care, about 75% had
improved functional capacity afterwards.
A further 17% maintained their existing
level of function, while functional
capacity deteriorated for 8% of recipients.
'Over the six years since its introduction,
more than 60% of recipients left the
program with an improved level of
functioning. And since 2005--06,
the proportion of care recipients who
returned to the community has been
about 54% overall.'
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