CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 1, January/February 2010
AFRICA
59
Stop press focus on RE-COVER study
Themilestone results of theRE-COVER™
study show a novel oral, direct thrombin
inhibitor dabigatran to be as effective as
well-controlled warfarin, with less bleed-
ing, in the treatment of acute venous
thromboembolism (VTE).
Compared to well-controlled warfarin,
dabigatran showed:
1
equal efficacy in the reduction of recur-
●●
rent VTE and deaths related to VTE
significantly fewer bleeding events
●●
confirmed liver safety.
●●
In New Orleans, USA, Boehringer
Ingelheim recently announced very
positive results from their landmark
RE-COVER™ study, the most advanced
trial programme assessing a novel oral
anticoagulant in development for acute
venous thromboembolism treatment.
These results were presented at the
American Society of Hematology annu-
al meeting
1
and published in the
New
England Journal of Medicine
online.
The oral, direct thrombin inhibitor,
dabigatran [150 mg twice daily (BID)],
showed equal efficacy compared to well-
controlled warfarin in preventing recur-
rent VTE (2.4% vs 2.1%, hazard ratio
1.10, 95% CI: 0.65–1.84,
p
<
0.001
for pre-specified non-inferiority margin).
With regard to safety, dabigatran demon-
strated a significant 37% reduction in
major or clinically relevant non-major
bleeding (
p
=
0.002). Major bleeding
was comparable between dabigatran (20
patients, 1.6%) and warfarin (24 patients,
1.9%). For any bleeds, dabigatran showed
a significant 29% reduction (
p
=
0.0002)
compared to warfarin. These outstand-
ing results were achieved without any
evidence of liver problems.
1
‘The results of RE-COVER™ are a
long-awaited breakthrough in the treat-
ment of VTE. Not only does dabigat-
ran offer an effective therapy to prevent
recurrent VTE, it does so with less
bleeding than warfarin’, commented
Dr Sam Schulman, principal investiga-
tor, Department of Medicine, McMaster
University, Hamilton, Canada. ‘Warfarin
is a highly effective therapy when well-
controlled within its narrow therapeutic
range, as in clinical trials, but in the real
world, sufficient control is rarely achieved
and maintained, leaving patients poorly
protected from VTE, or at risk of bleed-
ing. With dabigatran, we have a therapy
that protects our patients effectively and
safely, without the need for frequent labo-
ratory monitoring and dose changes.’
VTE, which includes deep-vein throm-
bosis (DVT) and its potentially fatal acute
complication, pulmonary embolism (PE),
is the third most common cardiovascular
disease worldwide (after coronary heart
disease and stroke).
2
VTE affects around
1.5 million Europeans
3
and three million
Americans
4
each year and kills more than
double the number of people as AIDS,
breast cancer, prostate cancer and traffic
accidents combined in Europe.
3
Earlier this year, the RE-LY
®
study
(18 113 patients in 44 countries world-
wide) showed groundbreaking results for
dabigatran, convincingly beating warfarin
in stroke prevention and treatment of
atrial fibrillation.
5
‘The results of the RE-COVER™
trial are very encouraging news for
VTE patients’, said Eve Knight, chief
executive of the patient organisation,
AntiCoagulation Europe. ‘Although
warfarin is an effective treatment, it impos-
es many restrictions on patients’ lives as
they require regular blood tests and dose
adjustments, and have limitations placed
on the food and drink they can consume.
In addition, the unpredictability of warfa-
rin places patients at risk of recurrent
clots or increased bleeding if it is not
sufficiently monitored. AntiCoagulation
Europe therefore welcomes the news that
dabigatran may offer a safer, more simple
alternative to warfarin for the treatment of
potentially life-threatening blood clots.’
Current guidelines recommend treating
acute VTE with anticoagulants to prevent
new blood clots from forming and old
ones from getting any bigger, as well as
reducing the risk of both post-thrombotic
syndrome and thromboembolic pulmo-
nary hypertension. These chronic diseases
can cause substantial illness and a high
economic burden.
6,7
Current standard
treatment involves the short-term use of a
low-molecular weight heparin for therapy
initiation in hospital, with subsequent
continuation of treatment with a vitamin
K antagonist (VKA, such as warfarin).
8
This provides a three-fold reduction in
recurrence of VTE, and extended duration
of therapy reduces this risk by 50%.
9,10
While VKAs are highly effective anti-
coagulants, they have multiple limitations,
which make maintaining patients within
the narrow therapeutic INR range of 2.0 to
3.0 challenging, requiring frequent moni-
toring to ensure patient safety and effi-
cacy. Even with close monitoring, as in a
clinical trial, patients spend only half their
time within this range and this tends to be
lower in the ‘real-world setting’.
11
Outside
of the narrow range, the rate of bleeding
is 44% and the rate of clotting is 48%.
12
Dabigatran provides effective, predict-
able and consistent anticoagulation with
a low potential for drug interactions and
no food interactions, and without the
need for routine coagulation monitoring
or dose adjustment. In contrast to VKAs,
which variably act via different coagula-
tion factors, direct thrombin inhibitors
achieve potent antithrombotic effects
by specifically blocking the activity of
thrombin (both free and clot bound), the
central enzyme in the process responsible
for clot (thrombus) formation.
In total, four trials involving 8 900
patients are exploring dabigatran in
VTE treatment: RE-COVER™ and
RE-COVER™ II in acute VTE, and
RE-MEDY™ and RE-SONATE™ in
the prevention of secondary VTE. The
results of RE-COVER™ and the very
favourable results of RE-LY
5
add to the
growing database of evidence support-
ing the efficacy and safety of dabigat-
ran across a wide range of acute and
chronic thromboembolic disorders from
the RE-VOLUTION
®
clinical develop-
ment programme involving over 38 000
patients.
‘Following the outstanding results
from the RE-LY
®
trial, these impres-
sive new data mean dabigatran has the
potential to benefit even more patients
and overtake warfarin as the treatment of
choice’, commented Dr Andreas Barner,
the chairman of the board of managing
directors of Boehringer Ingelheim. ‘We
look forward to submitting these results
to the regulatory authorities so that the
results of this landmark trial can be put
into a real-world setting.’
About RE-COVER
™
RE-COVER™ is a global, phase III,
randomised, double-blind, parallel-group
study evaluating whether oral dabigat-
ran (150 mg BID) is as effective and
