CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 9, October 2012
522
AFRICA
Drug Trends in Cardiology
New ESC guidelines on atrial fibrillation accept reality of next
generation of anti-coagulants
‘
The development of dabigatran and the
first results from the use of the novel
anticoagulant in the RE-LY trial mark
an extremely important time in medical
history; the first time in 75 years that
physicians have agents that are better
than the extremely effective warfarin in
secondary stroke prevention.’
Speaking at the 2012 European Society
of Cardiology (ESC) congress in Munich,
Germany, Prof Hans-Christoph Diener,
Department of Neurology, University of
Duisburg-Essen, Germany, also referred
to the daily reality of poor warfarin
control with low INR values resulting
in intracranial bleeds. ‘In fact warfarin,
despite its efficacy when INR levels are
well controlled (INR 2–3), due to its
very unpredictable pharmacokinetic and
pharmacodynamic profile, might not have
been approved if the novel anticoagulants
were first on the scene and warfarin
second.’ The conclusion that the new
anticoagulants are superior to warfarin
in stroke prevention, with a reduced risk
of intracranial bleeds, is now part of the
reality of the new ESC guidelines in
stroke prevention.
Prof Gregory Lip, Centre for
Cardiovascular Sciences, University of
Birmingham, UK, strongly endorsed
the ESC approach and pointed out that
the winds of change are altering stroke
prevention globally. ‘The latest American
College of Chest, Physicians Guidelines,
the Canadian Stroke Guidelines, the
AmericanHeartAssociationandAmerican
Stroke Association are in agreement that
most atrial fibrillation (AF) (non-valvular)
patients at intermediate to high risk of
stroke should receive one of these novel
agents in preference to warfarin’, Prof
Lip said. ‘We are also recommending a
practice shift to no antithrombotic therapy
if the CHA
2
DS
2
-
VASC score is zero, and
a “must-use” strategy in patients with a
CHA
2
DS
2
-
VASc score. This is a practice-
changing guideline’, Prof Lip concluded.
Experience with dabigatran
in one million patient-years of
treatment
At the ESC congress, Boehringer
Ingelheim announced that the combined
treatment experience with Pradaxa
®
has
crossed one million patient-years
1
in the
prevention of thromboembolic events
in patients after surgery, and patients
with non-valvular AF represented the
majority of patient years. This provides
the greatest body of clinical experience
among all novel oral anticoagulants. The
announcement reaffirms the confidence
physicians have in Pradaxa
®
to effectively
prevent stroke and systemic embolism in
patients with non-valvular AF and venous
thromboembolic events following hip- or
knee-replacement surgery.
One million patient-years of treatment
experience is unprecedented for a novel
oral anticoagulant and highlights the
broad adoption of dabigatran in more
than 70 countries worldwide following
regulatory approvals in stroke prevention
in AF. This level of clinical use shows
strong endorsement for the substantial
benefits Pradaxa
®
demonstrated in the
RE-LY trial, and for its positive benefit–
risk profile, as recently reconfirmed by
the European Medicines Agency.
Commenting on the news, Prof
Hans-Christoph Diener said ‘Preventing
ischaemic stroke is of utmost clinical
importance for healthcare professionals
treating patients with AF. With dabigatran
150
mg bid, clinicians have a treatment
available that prevents more ischaemic
strokes than well-controlled warfarin, and
it reduces intracranial haemorrhage at
the same time. The estimated number of
strokes prevented shows the relevance
of dabigatran as a safe and efficacious
preventive treatment for patients with AF
at risk of stroke.’
In addition, the RE-LY-ABLE trial,
which is a long-termmulticentre extension
of dabigatran treatment in patients with
AF who completed the RE-LY trial,
is close to its target of a further 28
months of active therapy with the two
dabigatran doses of 110 and 150 mg bid.
These results will reflect the outcomes
in patients continuously on dabigatran
for five years, and will be presented at
the 2013 American Heart Association
congress.
Reversing the effects of
dabigatran
For patients treated with dabigatran, a
range of options are available to reverse
the anticoagulant effect of treatment
and manage bleeding in an emergency
situation. Dabigatran is the only novel
oral anticoagulant that has the additional
option of removal from the blood system
via dialysis. Emergency dialysis can
remove about 60% of the dabigatran
concentration in four hours.
Furthertotheexistingreversalstrategies
already established in clinical practice, a
specific antidote may provide another
option for patient management during
rare critical-care situations where rapid
reversal may be helpful. Consequently
and as part of Boehringer Inghelheim’s
commitment to scientific innovation,
the Company is currently developing a
specific antidote to dabigatran etexilate
to broaden the reversal options available
to physicians.
J Aalbers
