CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 5, September/October 2010
AFRICA
301
Effective single-drug approach is welcomed for deep-vein thrombosis treatment
Rivaroxaban protection is non-inferior and safe when compared to low-molecular weight heparin and warfarin
Results from the EINSTIEN-DVT trial
were announced at the recent ESC 2010
congress, showing the therapeutic equiva-
lence of rivaroxaban (15 mg twice daily
for three weeks, followed by 20 mg once
daily) to current standard therapy in treat-
ing and preventing further venous throm-
botic events (VTE).
Prof Harry Buller, Academic Medical
Centre, Amsterdam presented the results
in the hot-line session and pointed out that
this trial is the largest ever undertaken in
deep-vein thrombosis (DVT), with 3 449
patients entered into the study from 32
countries.
‘EINSTEIN-DVT was designed as a
non-inferiority trial and although open
label, all events were adjudicated blind-
ly. The primary-efficacy outcome was
defined as symptomatic recurrent VTE:
composite of recurrent DVT, non-fatal or
fatal pulmonary embolism (PE)’, he said.
This trial has now shown that rivar-
oxaban taken orally is as effective in
preventing recurrence of symptomatic
VTE as well-managed patients receiving
the current standard therapy of injectable
low-molecular weight heparin (LMWH),
enoxaprin or fondaparinux, and an oral
vitamin K antagonist, chiefly warfarin.
While scientific publication of the full
results will still follow, Prof Buller present-
ed substantiating data for the conclusions.
‘The first symptomatic recurrent VTE
occurred in 3% of patients receiving stand-
ard therapy, compared to 2.1% on rivar-
oxaban (hazard ratio of 0.68). This differ-
ence was significant and reached our pre-
set standard for non-inferiority’, he said.
‘Importantly, there was no difference in
the principal safety outcome, measuring a
composite of major and non-major clini-
cally relevant bleeding events (8.1%in both
treatment arms). Rivaroxaban did however
show a tendency to cause fewer major
bleeds (14 in the rivaroxaban arm and 20
in the enoxaparin/warfarin arm)’, Prof
Büller said. Net clinical benefit, a param-
eter of primary efficacy plus no major
bleeding, favours rivaroxaban therapy.
Overall control of patients receiving
enoxaprin and vitamin K antagonists was
good, with 57% within the targeted INR
range of 2 to 3, and this increased to 60%
at three months after the trial. The trial was
conducted over a 12-month period.
Discussing the results, Eve Knight of
Anti-Coagulant Europe, the non-profit
organisation that represents the interests
of patients who have to take anti-coagulant
therapy following a VTE, pointed out that
patients have great difficulty with the
cumbersome warfarin therapy.
‘You are continually having to visit
the clinic and have blood drawn for INR
monitoring. You have to watch your food
and drink intake, which greatly impacts on
quality of life. VTEs affect young people
who are still very active, the patients in the
EINSTEIN trial were about 56 years of
age, causing ongoing disruption to one’s
working life and can affect career progress
very badly’, she stressed.
Rivaroxaban is available in South
Africa for the prevention of DVT follow-
ing orthopaedic surgery and Bayer will
be making representation to regulatory
authorities across the world for the use
of this drug in treating both primary and
secondary DVT. ‘As this drug has the
potential to change clinical practice, it
may well receive priority attention’, Dr
Berkowitz, Bayer Schering Pharma medi-
cal director noted.
rin arm of the RELY trial, the quality
of warfarin treatment was calculated by
establishing the time in therapeutic range
(TTR). The average individual time in
therapeutic range (iTTR; with a target
INR of 2.0–3.0) for patients randomised
to warfarin was 64%, which is a similar
level of control to that seen in recently
published prospective, randomised trials.
There were considerable variations in
TTR among the trial centres across the
44 participating countries. In the present
sub-group analysis, each centre’s average
TTR (cTTR) was calculated as the aver-
age of all individual patients’ TTRs in the
warfarin group.
The distribution of cTTRs across study
centres was investigated and interquar-
tile limits were identified. The quartiles
of cTTR for the warfarin patients were
<
57.1%, 57.1–65.5% and
>
72.62%.
Outcomes were assessed across the three
treatment arms (dabigatran etexilate 110
mg BID, 150 mg BID, and warfarin).
Results demonstrated that:
3
•
Dabigatran etexilate 150 mg BID was
superior to warfarin in the reduction of
stroke and systemic embolism, inde-
pendent of the level of centre-based
INR control.
•
Dabigatran etexilate 110 mg BID was
similar to warfarin in the reduction of
stroke and systemic embolism, with
lower rates of major bleeding, inde-
pendent of the level of centre-based
INR control.
•
Both dosages of dabigatran etexilate
were superior to warfarin in terms of
intracranial haemorrhage (ICH), irre-
spective of centre-based INR control.
For further information on dabigatran
please contact Sue Thomas (Medical
Information, Boehringer Ingelheim) on
(011) 348-2514.
J Aalbers, Special Assignments Editor
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2010;DOI:10.1016/S0140-6736(10)61194-4.
