CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 10, November 2012
576
AFRICA
Benefits of dabigatran maintained for more than two years
Prevention of stroke in patients with
non-valvular atrial fibrillation was
sustained over more than two years’ use
of the novel oral anticoagulant drug,
dabigatran, according to data from the
first long-term study of these new agents.
The results from the RE-LY-ABLE
(
Long-term Multi-centre Extension of
Dabigatran Treatment in Patients with
Atrial Fibrillation) study
1
were presented
at the American Heart Association (AHA)
scientific sessions 2012.
RE-LY-ABLE is an extension of
the previously published RE-LY study,
following which, 5 851 patients continued
to receive dabigatran 110 or 150 mg bid
(
Table 1).
1
Presenting the results, Prof
Stuart Connolly, director of Cardiology at
McMaster University, Hamilton, Canada,
said: ‘RE-LY-ABLE shows the results
seen in RE-LY continue to be observed
during long-term follow up. We see similar
rates of stroke or systemic embolism and
comparable rates of major bleeding, with
similar rates of intracerebral bleeding and
intracranial haemorrhage’ (Table 2).
‘
Most patients with atrial fibrillation
(
AF) need life-long anticoagulation
treatment to be protected from ischaemic
stroke. The unique long-term data we now
have for dabigatran are reassuring for
both patients and physicians’, said Prof
Connolly. He added that the combined data
of RE-LY and RE-LY-ABLE provide more
than four years of information on efficacy
and safety.
2,3
RE-LY-ABLE showed that there was
a consistent reduction in ischaemic and
haemorrhagic stroke with both doses of
dabigatran versus a blinded control group
(
Table 3). Additionally, the incidence of
major bleeding was 3.74% per year in
patients receiving dabigatran 150 mg bid
and 2.99% per year in those treated with
110
mg bid compared with controls. Rates
of intracranial bleeding were 0.33 and
0.25%
per year in the 150- and 110-mg
groups, respectively.
The rate of myocardial infarction was
0.69%
per year in patients treated with 150
mg bid and 0.72% per year in the 110-mg
bid group. ‘This is consistent with the
results seen in RE-LY’, Prof Connolly said.
Based on these data, Prof Connolly
commented, ‘The consistent incidence of
ischaemic and haemorrhagic stroke as well
as rates of intracranial bleeding observed
indicate that dabigatran provides on-going
protection of the brain. Furthermore, both
doses of dabigatran had similar net clinical
benefit and mortality rates. In RE-LY-
ABLE, the safety profile of dabigatran
was consistent with the findings from the
RE-LY trial.’
Commenting after the presentation, Prof
Gregory Lip, professor of Cardiovascular
Medicine at the University of Birmingham,
UK said, ‘The results of RE-LY-ABLE will
be a valuable contribution to evidence-
based decision making in the selection of
a treatment for patients with AF over the
longer term. Despite the prevalence of
AF and the five-fold increase in the risk
of stroke, there remains significant scope
for improvement in reducing the risk of
stroke in the AF population. RE-LY-ABLE
will serve to give added confidence to
physicians in their prescribing decisions
when managing this increasingly prevalent
condition over the long term.’
Net benefit analysis
Prof Connolly also presented a net benefit
analysis at theAHAof all 12 091 dabigatran-
treated patients in both RE-LY and RE-LY-
ABLE. This showed that in patients treated
over more than four years, the hazard ratio
for stroke and systemic embolism was 0.81
(95%
CI = 0.66–0.96), with rates of 1.25%
per year if patients received dabigatran 150
mg bid and 1.50% per year in the 110-mg
bid group. Prof Connolly commented:
‘
There is now convincing data that there is
no difference in total mortality between the
two doses of dabigatran over a mean follow
up of 4.3 years.
Discussing this net clinical benefit, Prof
John Eikelboom, Department of Medicine,
McMaster University, Hamilton, Canada,
said ‘Both high (150-mg bid) and low
(110-
mg bid) doses (of dabigatran) provide
similar net benefit over warfarin. The
higher dose achieved this clinical benefit
through (superior) stroke prevention
while the lower dose achieved it through a
reduction in bleeding. So, the picture here
is one of complete internal consistency.
Clinicians can be confident that if they
start a patient on dabigatran, it will remain
a good decision three to four years later.’
J Aalbers
1.
Connolly SJ,
et al
.
Presented 7 November
2012
at the American Heart Association
Scientific Sessions 2012.11.15.
2.
Connolly SJ,
et al
.
N Engl J Med
2009;
361
:
1139–1151.
3.
Connolly SJ,
et al
.
N Engl J Med
2010;
363
:
1875–1876.
TABLE 2. PATIENTS IN RE-LYAND RE-LY-ABLE
Treatment
Dabigatran
150
mg bid,
n
(%)
Dabigatran
110
mg bid,
n
(%)
Randomised to RE-LY
6015
6076
Completed RE-LY and still receiving dabigatran
4492 (75)
3397 (75)
Patients enrolled into RE-LY-ABLE
2914 (86)
2937 (87)
Completed RE-LY-ABLE and still receiving dabigatran
2511 (86)
2508 (85)
Continued in RE-LY-ABLE beyond 28-month visit
1082 (44)
1104 (44)
TABLE 3. OUTCOMESWITHTWO DABIGATRAN DOSES COMPARED IN RE-LY-ABLE
Event
Dabigatran
150
mg (%/year)
Dabigatran
110
mg (%/year)
Hazard ratio
(95%
CI)
Stroke/systemic embolism
1.46
1.60
0.91 (0.69–1.20)
Major bleed
3.74
2.99
1.26 (1.04–1.53)
Intracranial bleed
0.33
0.25
1.31 (0.68–2.51)
Death
3.02
3.10
0.97 (0.80–1.19)
Stroke, systemic embolism, MI, pulmonary
embolism, major bleed or death
7.36
6.89
1.07 (0.94–1.22)
TABLE 1. THE RE-LY-ABLE STUDY
Purpose
RE-LY-ABLE (Long-term Multi-centre Exten-
sion of Dabigaran Treatment in Patients with
Atrial Fibrillation study) included patients who
completed the RE-LY trial and were recruited
into a cluster-randomised trial to evaluate the
long-term effects of continued treatment with
dabigatran.
Objective
To establish the long-term safety of dabigatran
and to assess its efficacy on the prognosis,
cardiovascular risk profile and quality of care
in patients with atrial fibrillation.
