The Specialist Forum Volume 13 No 11 November 2013 | Page 76

HYPERTENSION

NOACs: from bench to bedside

N

ew oral anticoagulants (NOACs) have been shown to be at
least as effective in prevention and treatment of deep vein
thrombosis (DVT) and pulmonary embolism (PE), compared
to previous therapy standards such as heparin or warfarin, according
to Dr Jan Beyer-Westendorf, head of the Thrombosis Research Unit,
Centre for Vascular Medicine at the University Hospital Carl Gustav
Carus in Germany.
Despite concerns that have been raised over the past year about
major bleeding events associated with anticoagulants, Dr BeyerWestendorf stressed that the risk of bleeding should be weighed
against the risk of venous thromboembolism (VTE) events. In his view,
the advantage of using NOACs far outweighs any other risks.

Weighing the risks
When Dr Beyer-Westendorf and his colleagues started using NOACs
for VTE prevention after hip or knee replacement surgery, they met
with resistance from surgeons who felt that with these new drugs,
the balance between the risk of bleeding and the risk of DVT and VTE
was still unclear, despite very convincing trial data, which indicated
a relative risk reduction for VTE of up to 40% without the downside
of increased bleeding complications. To address their concerns, Dr
Beyer-Westendorf and his unit undertook a retrospective study in
which they reviewed the medical records of more than 1000 patients
who were treated using the NOAC rivaroxaban and compared this data
with data from over 3500 orthopaedic patients receiving injectable
thromboprophylaxis during the three year period before the introduction of rivaroxaban.
In their cohort study, they compared the efficacy and safety of rivaroxabin with injectable thromboprophylaxis by focusing on the following:
• Whether a patient had an established DVT or pulmonary embolism
• Safety issues like major bleeds
• Patient outcomes
• Types of surgery
• Wound infections
• Length of hospital stay.
The results indicated that there was a 48% relative risk reduction
against low molecular weight heparin and a 60% risk reduction against
fondaparinux thromboprophylaxis. “You might say most patients,

after orthopaedic surgery will develop distal DVT, which might be
un­
important events? But if you look at proximal, thigh, pelvic DVTs
or pulmonary embolism, death from VTE, there is still a risk reduction of between 30%-50%, when changing to rivaroxaban,” said Dr
Beyer-Westendorf.

Bleeding versus risk reduction
Studies have indicated that between 10%-12% of patients experience
bleeding at the wound site, while at the same time there was a 40%
risk reduction in symptomatic thromboembolic events as well as a 40%
risk reduction in significant events and around 30% in symptomatic
VTE events.
“In our daily care registry, we also did not find any indication that this
superior effectiveness was achieved with the downside of increased
bleeding risks. If anything, we also detected a decrease in major
bleeding complications including wound bleeding and less surgical
complications requiring revision surgery, which contributed to a shorter
hospital stay in patients receiving rivaroxaban thromboprophylaxis”, Dr.
Beyer-Westendorf stated.

Treatment of acute VTE
The Einstein trials, which included more than 8000 participants with
either acute DVT or PE and compared the outcomes of patients treated
with heparin for a few days followed by warfarin, with those treated with
rivaroxaban, showed a 11% risk reduction in recurring VTEs and an impressive 46% relative risk reduction for major bleeding. The researchers concluded that rivaroxaban was at least as effective in preventing
recurring VTE events, but was much safer than the previous standard
therapy heparin and wafarin. In essence, this means that the use of
rivaroxaban reduced the risk of an unfavourable outcome such as recurring VTE or major bleeding by 23%. The findings of this study had
a huge impact on the daily care situation, said Dr Beyer-Westendorf,
adding that another advantage of using rivaroxaban is that the recurring
VTEs and bleeding are prevented simultaneously.

Treating ‘frail’ patients
In daily care, noted Dr Beyer-Westendorf, patients who are elderly and
frail often are considered non-eligible for warfarin treatment. These
patients may currently be treated with daily injections of heparin for a
few months. The problem on the one hand is that these patients are at
high risk of recurrent DVTs and should therefore, be placed on more
intense anticoagulation, but on the other hand, they are also more at
risk of developing major bleeding.
“It therefore makes very little difference whether or not you give these
patients more or less anticoagulation, because these patients will have
problems. It is, therefore, correct to be very sceptical of using warfarin
on these kinds of patients,” said Dr Beyer-Westendorf, adding that in
circumstances like these, the best option is to change to another drug.
In the Einstein trials, more than 1 500 patients were fragile. If you
look at these high-risk patients specifically, rivaroxaban achieved a
relative risk reduction for recurrent VT E of 32%, while at the same
time reducing the risk for major bleeding by an impressive 73%. Dr.
Beyer-Westendorf concluded that the positive risk-benefit profile of
rivaroxaban also extends to the high-risk population of elderly, fragile
patients with acute VTE.

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November 2013 | Cardiology & Stroke Forum