CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 5, September/October 2011
AFRICA
283
Drug Trends in Cardiology
Namibia becomes first country in Africa to launch dabigatran
etexilate for atrial fibrillation
On 1 August 2011, Namibia became the
first African country to make available
Boehringer Ingelheim’s novel oral blood
thinner, Pradaxa (dabigatran etexilate), the
first real breakthrough in anticoagulation
therapy in over 50 years. The Namibian
Medicines Control Council has approved
the prophylactic use of dabigatran etex-
ilate for the prevention of stroke in
patients with atrial fibrillation (AF),
the most common type of arrhythmia.
AF affects around 1% of the total
population and one in four adults over
the age of 40 will develop the condition
during their lifetime. AF raises the risk of
stroke five-fold.
Speaking at the launch in Windhoek,
Dave Arnold, marketing director of
Boehringer Ingelheim South Africa, said
that dabigatran etexilate would meet
currently unmet therapeutic needs in AF
patients. These unmet needs are especially
pronounced in elderly patients who are at
greater risk of bleeding.
‘The vitamin K antagonist (VKA)
warfarin, currently the gold standard in
anticoagulation treatment, while effec-
tive, has many limitations in respect of
food–drug and drug–drug interactions.
Dabigatran etexilate therefore offers a
unique opportunity to address these gaps
in a safe and efficacious manner and has
the potential to make a significant differ-
ence to AF patients at risk of stroke. That
international guidelines were updated
even before the drug became available
attests to this.’
Dr IWP Obel, an electrophysiologist
in private practice at Milpark Hospital,
Johannesburg, and one of the doyens of
cardiology in South Africa, told guests
that the advent of dabigatran etexilate
is good news for Namibia. ‘INR testing
is not practical in Africa and as a result,
many patients requiring anticoagulation
currently don’t receive it. The increased
stroke risk associated with AF translates
into an approximately 50% mortality rate
at one year, with an associated heavy
personal health and economic burden.’
Appropriate anticoagulation therapy
can prevent AF-related stroke, but the
use of warfarin, although it is effective, is
often difficult and sometimes impossible.
‘VKA prophylaxis costs include the close
monitoring required to manage the many
complications consequent on warfarin’s
narrow therapeutic window, slow onset
of action and many food–drug and drug–
drug interactions’, said Dr Obel. ‘Frequent
dose adjustments are required and some
patients are simply resistant to it.’
Patients who fall outside the target INR
range are at risk of catastrophic events.
This is because warfarin has two contrast-
ing actions – as it decreases the risk of
thromboembolic events, it increases the
risk of bleeding.
Dabigatran etexilate removes the
dangers of warfarin, and clearly designed
protocols allow for patients currently on
warfarin to be easily switched to dabi-
gatran etexilate, which has a fast onset of
action and achieves a good and predict-
able anticoagulation effect within two
hours of warfarin discontinuation. It has
no meaningful drug and food interactions,
and notably, no potential for cytochrome
P-
450
-related drug interactions.
The RE-LY study
Reviewing the Randomised Evaluation
of Long-Term Anticoagulation TherapY
(RE-LY) study, published in the
New
England Journal of Medicine
in 2009,
which evaluated dabigatran etexilate
versus warfarin in AF patients, Dr Obel
described it as a ‘remarkable’ trial, involv-
ing over 18 000 AF patients with one or
more additional risk factors for stroke.
The median duration of follow up was
two years, with stroke or systemic embo-
lism the primary outcome. The second-
ary endpoint was net clinical benefit
based on a composite of stroke, systemic
embolism, myocardial infarction, major
bleeding, pulmonary embolism and death.
Major bleeding events were the primary
safety measure. Patients were randomised
to either 110 or 150 mg of dabigatran
etexilate twice daily or to adjusted-dose
warfarin.
‘The efficacy results were really excit-
ing’, said Dr Obel. ‘The time to first stroke
or systemic embolism was significantly
35% longer on 150 mg dabigatran etex-
ilate twice daily, suggesting that it prevents
three out of four AF-related strokes.’
‘While dabigatran etexilate in both
doses was superior to warfarin, it is the
higher dose that really makes the differ-
ence. It was effective across a wide range
of patients and its efficacy was not affect-
ed by age, gender and co-morbidities. It
was advantageous relative to warfarin in
respect of both total bleeding and life-
threatening bleeds, and when it came to
intracranial bleeding, our greatest fear,
there were major advantages with both
doses.’
Adverse effects were for the most part
comparable between the two agents. The
only side effect that was significantly
more common in those taking dabigatran
etexilate was dyspepsia.
Dr Obel therefore feels that dabigatran
etexilate represents a major advance in
anticoagulation therapy. ‘It requires no
INR monitoring or dose titration. It is
taken orally, either with or without food.
There is no delay in its onset of action and
it is highly effective and safe over a wide
range of patients. RE-LY showed that
dabigatran etexilate provides great safety
and efficacy where it really counts’, he
concluded.
Dr Kevin Ho, medical director of
Boehringer Ingelheim South Africa, said
that dabigatran etexilate also shows great
promise in the treatment of venous throm-
boembolism (VTE). In the RE-COVER
trial, the 150-mg dose closely mirrored
warfarin in terms of efficacy and was
thus non-inferior, while safety outcomes
favoured dabigatran etexilate. ‘In acute
VTE, dabigatran etexilate provides a
convenient, oral, fixed-dose treatment with
the potential to replace warfarin’, he said.
Peter Wagenaar, Gauteng correspondent
1.
ConnollySJ,EzekowitzMD,YusufS,Eikelboom
J, Oldgren J, Parekh A,
et al
. Dabigatran
versus warfarin in patients with atrial fibril-
lation.
N Engl J Med
2009;
361
: 1139–1151.
