CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
300
AFRICA
Focus on 2010 ESC Congress
New ESC guidelines and data on dabigatran
In a major symposium on atrial fibril-
lation (AF), Prof John Camm, head of
the Department of Cardiac and Vascular
Sciences at St Georges, University of
London, pointed out that atrial fibrillation
cases are set to double as populations age.
‘One in four adults 40 years of age will
develop atrial fibrillation in their lifetime.
The consequences are tragic and devastat-
ing, with a five-fold increase in the risk
of having a stroke’, he said. Stroke is also
more likely to be severe and fatal in these
patients; those who survive face persistent
neurological deficits, persistent disability
and poorer functional performance.
1,2
The European Society of Cardiology
(ESC) has now issued revised practice
guidelines for the management of atrial
fibrillation, including guidance on the
role of a novel oral treatment, dabigatran
etexilate, for the prevention of stroke and
systemic embolism in patients with atrial
fibrillation.
Dr Jeffrey Friedman, therapeutic head
of cardiovascular products at Boehringer
Ingelheim in the USA confirmed that the
US Food and Drug Administration (FDA)
has granted a priority review designation
for dabigatran etexilate for the prevention
of stroke in AF. A priority review designa-
tion is given to new drugs that are expect-
ed to offer major advances in treatment,
or provide a treatment where no adequate
therapy exists. (An FDA advisory commit-
tee met on September 20 to review and
discuss dabigatran etexilate data.)*
In addition to the USA, the registration
process for dabigatran etexilate is under-
way in Europe, Japan and other countries.
The company expects to receive market-
ing authorisation for dabigatran etexilate
in these countries by the end of 2010 or
the beginning of 2011.
Dr Friedman pointed out that
Boehringer Ingelheim has a long-term
commitment to stroke prevention, with
the development of Actilyse in 1982,
Asasantin retard in the 1990s, and more
recently, Micardis for the prevention of
stroke and myocardial infarctions in the
early 2000s. ‘Telmisartin is still the only
ARB with a broad claim for cardiovascu-
lar protection, based on the ONTARGET
studies’, Dr Friedman noted.
Discussing the latest RELY results,
3
Dr
Jonas Oldgren from the Uppsala Clinical
Research Centre, pointed out that all
centres, even those with poorer INR
control determined from their patients’
time-in-treatment data, achieved better
results using dabigatran than warfarin
in the reduction of stroke and systemic
embolism.
As might be expected in the poorer
warfarin-control setting, both dosages
of dabigatran demonstrated superior
advantages over warfarin in the reduc-
tion of secondary outcomes, such as the
composite of all cardiovascular events,
total mortality and major bleeding. The
secondary outcome results in centres
with better INR control were comparable
between dabigatran and warfarin. ‘Local
standards of care do therefore affect the
benefits of switching to new treatment
strategies’, Prof Oldgren said.
For each patient involved in the warfa-
*Stop press
FDA meeting on dabigatran
One of cardiology’s fondest wishes
moved closer to fulfillment as an
FDA advisory panel unanimously
recommended approval of a potential
replacement for warfarin in one of the
most common heart disorders. Barring
any unforeseen damning revelations
about the drug, the FDA’s approval of
the oral thrombin inhibitor dabigatran
(Pradaxa, Boehringer Ingelheim) for
stroke prevention in atrial fibrillation
is all but certain.
The panel, with its nine voting
members, made the decision based
on what’s generally seen as the
well-designed, solidly executed, 18
000-patient Randomized Evaluation
of Long-Term Anticoagulant Therapy
(RELY) trial, which showed dabigatran
was non-inferior to warfarin at a lower
dosage and superior at a higher one for
preventing thromboembolic stroke in
paroxysmal or permanent AF.
Debate among the advisory panel
throughout the day was tame; there
were few criticisms of the RELY
trial’s design, little disappointment in
the results, and clear enthusiasm for
replacing warfarin in such a wide-
spread indication.
The panel wasn’t charged with
voting on a question that provided
some of the only suspense throughout
the day; whether the approval should
include only the higher dose, which
demonstrated superiority in RELY,
or perhaps both dosage levels. They
voted informally nonetheless, with
those expressing a preference for both
dosages (generally wanting to give
clinicians more flexibility) edging out
those favouring only the higher dose.
Some of the latter panelists felt the
lower dose would become the default
for clinicians concerned about safety
but at the expense of efficacy.
Warfarin is distinguished as being
one of the oldest, most widely used,
most effective, and most disliked
drugs in cardiology: it dramatically
cuts ischaemic stroke risk in AF but
generally requires tight anticoagula-
tion monitoring to get the dosage right,
which can be arduous for patients and
the healthcare system. Patients must
also banish a lot of healthy, vitamin
K-containing foods from their diet.
The kicker with dabigatran, even
when ‘non-inferior’ to warfarin, is
that it doesn’t require anticoagulation
monitoring, or major diet changes, for
that matter. And, as the trial suggested
and some panelists agreed, at the high-
er dose it seems more stroke-preventive
than warfarin.
As previously reported by heart
wire
,
RELY compared the two dabigatran
dosage levels against a convention-
al warfarin regimen for the stroke-
prevention indication. Dabigatran was
non-inferior to warfarin at the lower
dosage and superior at the higher one,
the latter achieving a 34% decline in
risk (
p
<
0.001) over a median of two
years.
Source: theheart.org
