CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 5, September/October 2011
284
AFRICA
New insights and results from the RE-LY trial
The RE-LY trial with dabigatran has
provided clinicians worldwide with a new
benchmark standard for anticoagulation
and stroke prevention in atrial fibrilla-
tion. This view was presented at the 2011
European Society of Cardiology (ESC)
congress by Dr Gregory Lip, profes-
sor of cardiovascular medicine at the
University of Birmingham, who is well
placed to evaluate clinical expectations
for these new agents. He has acted as
clinical advisor to the UK Institute of
Health and Clinical Excellence (NICE)
Guidelines on Atrial Fibrillation (AF)
Management and has served as stroke
prevention head for the 2010 ESC guide-
lines on AF management.
‘There is an urgent need for clini-
cians to adjust to this paradigm shift in
stroke prevention, based on the insights
and results from RE-LY with dabigatran,
currently the only registered anticoagulant
for AF.
1,2
In addition, the emerging data on
the oral factor Xa inhibitors, Apixaban
and Rivaroxaban will also influence clini-
cal approaches to the use of anticoagu-
lants in a wide variety of clinical settings.’
Two new RE-LY sub-studies were
released at the ESC and showed that
dabigatran provided consistent benefits in
reducing stroke inAF, regardless of wheth-
er the patients were on aspirin, clopidog-
rel or other concomitant therapies, such
as the anti-arrhythmics, amiodarone and
verapamil.
3,4
Dr Lip pointed out that the
antiplatelet agent, aspirin has little benefit
in stroke prevention inAF, and may in fact
be less safe than warfarin, especially in
the elderly.
5
Co-chair of this special ESC symposi-
um, Dr ElaineHylek, of BostonUniversity,
USA, pointed out that warfarin and other
vitamin K antagonists (coumarin) are very
effective, reducing overall risk of strokes
by 68%. This benefit dwarfs the benefit
shown in statin trials in the early 1990s.
‘Despite this, warfarin is under-used,
with only 50% of patients in the USA
and Swedish registries being treated with
warfarin. The perception of bleeding risk
and difficulties around availability with
food and other drugs seems to discourage
warfarin use’, she noted. This under-
use is aggravated by the fact that in
the ACTIVE-W trial, it was shown that
patients on warfarin need to be within the
target INR (2–3) for 58 to 65% of the time
in order to achieve these benefits.
Also, some patients have low INR
variability, in contrast to other individu-
als who show high variability. INR vari-
ability is therefore highly individualised,
a factor that clinicians and patients must
understand.
‘Dabigatran in the RE-LY trial of
stroke in non-valvular atrial fibrillation
showed that dabigatran etixilate 150 mg
bid further reduced the risk of stroke or
systemic embolism by an additional 35%
compared to well-controlled warfarin’,
Dr Lip stressed. This was achieved with
a similar rate of bleeding compared to
warfarin.
The 110-mg bid dose of dabigatran
was non-inferior to warfarin with a
lower bleeding risk. Interestingly, there
is a suggestion, on further analysis of the
RE-LY data, of an age interaction with
dabigatran, such that dabigatran 110 mg
twice dailywas associatedwith a lower risk
of major bleeding compared to warfarin
in patients under 75 years of age, and with
a similar risk in those older than 75 years.
The higher dose was associated with
a trend towards a higher risk of bleeding
in those older than 75 years. Importantly,
this was due to the rate of extracranial
haemorrhages being slightly higher, rath-
er than being due to intracranial haemor-
rhages, which were consistently reduced
with dabigatran compared to warfarin,
irrespective of age.
6
‘This can give reassurance for the use
of the 75-mg bid dose in the super-elderly
(
≥
75 years)’, Dr Lip noted. ‘There is also
some data to suggest that patients with
paroxysmal AF do better on the 110-mg
dose’, Dr Lip added.
In conclusion, Dr Lip noted that the
advent of dabigatran has moved the pivot
point of oral anticoagulant benefit versus
bleeding to a lower CHADS
2
score of
above 0, and if using the newer CHA
2
DS
2
-
VASc score, of 1 and above. This means
that oral anticoagulation should be used
more widely to the benefit of more
patients, thereby effectively reducing their
risk of stroke.
Comments from attending
South African experts
Dr Adri Kok, private practice physician,
Benoni, Gauteng
As a physician, I am very aware that atrial
fibrillation is still a poorly diagnosed risk
factor for arterial embolisation and stroke.
It is a preventable cause of stroke and
the availability of a safer-than-warfarin
anticoagulant in the form of dabigatran, a
direct thrombin inhibitor, is an important
development.
The effective level of anticoagulation
with warfarin is difficult to attain in the
majority of patients and often results in
bleeding complications and hospitalisa-
tion for treatment of excessive anticoagu-
lation. Apart from the inadequate stroke
prevention due to poor INR control,
these hospitalisation events significantly
contribute to cost, as do the INR determi-
nations and bleeding complications.
To have a safer and effective alterna-
tive is extremely useful and will improve
the successful management of these high-
risk patients. At present we are very
careful of exposing an older patient to
warfarin therapy as the bleeding risk may
outweigh the potential benefit. With the
results of the RE-LY trial, dabigatran
provides us with a safe, effective and reli-
able alternative for these patients.
Dr Jeff King, specialist physician, private
practice, Gauteng
Now, for the first time, we have a comple-
ment of drugs that can be used effectively
to more safely reduce the risk of stroke
in AF. While warfarin is cheap, tried and
tested, it still has potential cost-ineffective
life-threatening complications, of which
clinicians are well aware.
There is a clinical need to give
earlier and greater attention to the AF
co-morbidities as risk managed by the
CHA
2
DS
2
-VASc score. These AF patients
that I typically see are identified but not
completely, by the CHA
2
DS
2
-VASc score,
including the middle-aged and elderly
patients in whom rhythm disturbances,
with lone atrial fibrillation, are a conse-
quence of the ageing process. Secondly,
I see diabetics, hypertensives, obese
patients, ischaemic heart patients with
myocardial dysfunction and idiopathic
dilated cardiomyopathy, with or without
cardiac failure.
It is important to manage under-recog-
nised aggravating risks such as exces-
sive alcohol intake and obstructive sleep
apnoea. Trials are awaited for the treat-
ment of non-valvular associated AF.
A matter of great concern to me is the
delayed access or denial of access to these
