CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 6, July 2013
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AFRICA
warfarin performed similarly in terms of
bleed rates; however, the rivaroxaban arm
displayed a lower incidence of intracranial
bleeds. ‘Oral anticoagulation is the basis
for almost all AF patients and NOACs
should be the first choice in newly treated
patients’, concluded Dr Mochmann.
Dr Beyer-Westendorf’s musings were
directed to the efficacy and safety of
NOACs in daily care, with the opening
statement ‘… choose one NOAC with the
broadest range indicated. Get experience
…, if you are unhappy, change to another
NOAC’. Dr Beyer-Westendorf also
considered differences in clinical trial
results compared to the use of these
agents in daily practice.
Venous thromboembolism
Globally, venous thromboembolism
(VTE) is estimated to cause at least three
million deaths a year. Known conse-
quences of VTE include fatal pulmonary
embolism (PE), risk of recurrent VTE,
post-thrombotic syndrome (PTS), chronic
thromboembolic pulmonary hypertension
(CTPH) and a reduced quality of life.
Within a five-year period after idiopathic
deep-vein thrombosis (DVT), approxi-
mately one-third of patients will develop
PTS. This is characterised by pain, oede-
ma, hyperpigmentation, eczema, varicose
collateral veins and venous ulceration.
Drawbacks of current VTE treatment
options (vitamin K antagonists and
heparin) are initial parenteral treatment,
and its poor acceptance by patients.
Barriers presented by the use of vitamin
K antagonists in the treatment and
prevention of VTE include the narrow
therapeutic range, inter-patient variability
in dose response, multiple food and
drug interactions, and the requirement
for regular coagulation monitoring and
dose adjustment. Major bleeds with poor
outcome are common.
An FDA analysis performed in 2011
found the anticoagulants to have the most
serious adverse events. Warfarin is at the
top of this list, despite having been used
for 50 years. The complicated dosing
regimen of warfarin is not ideal, with long
hospital stays associated with overdose.
Major orthopaedic surgery represents
an increased risk of DVT and anticoagu-
lants are routinely used to prevent these
potentially life-threatening complications.
Dr Beyer-Westendorf considered the net
clinical benefit of the use of NOACs
in VTE prevention after orthopaedic
surgery, particularly rivaroxaban, apixa-
ban and dabigatran. All of the NOACs
were as good as, or better than, heparin in
terms of prevention of symptomatic VTE
and risk of bleeding.
Data from his retrospective ORTHO-
TEP registry consisting of three cohorts,
including 5 000 patients undergoing hip-
or knee-replacement surgery, indicate
that replacing heparin with rivaroxaban
results in a symptomatic DVT relative
risk reduction of up to 60%. In terms
of proximal DVT, PE and death from
VTE, rivaroxaban provides a relative risk
reduction of up to 30% compared to
heparin of fondaparinux, with equivalent
safety.
ForVTE therapy, rivaroxaban is rapidly
becoming the standard in many countries,
with the benefits of a simpler dosing
regimen (15 mg bd for three weeks, 20
mg od thereafter) than warfarin, and with
no adaptations required for gender and
old age. Patients are unable to overdose
on rivaroxaban due to a ‘ceiling effect’, a
point where no further rivaroxaban can be
absorbed. Combined data on rivaroxaban
from the EINSTEIN DVT and EINSTEIN
PE trials present a relative risk reduction
of 46% for major bleeds and 11% for
recurrent VTE.
Furthermore, data from a large
prospective daily-care registry of NOACs
(run by Dr Beyer-Westendorf in Germany)
seem to indicate a rather benign pattern of
bleeding complications: of all NOAC
bleeds seen in this registry, 62% were
minor and did not require any treatment,
and 33% were non-major but clinically
relevant bleeds, most of which could be
treated without surgery or interventions.
Only 5% were major bleeds, most of
which were treated by red blood cell
transfusions, PCC or interventions.
There was an 8% mortality rate within
the major-bleed group, which is much
lower than the mortality rate with major
warfarin bleeds seen in daily care.
In his concluding statements, Dr
Beyer-Westendorf intimated that the half-
life and elimination rates of NOACs are
very similar to low-molecular weight
heparin (LMWH) and are therefore
convenient for use in planned surgery,
with good data for the safety profile.
Treatment is interrupted at least 24
hours prior to surgery, depending on
the thromboembolic and bleeding risk
of the procedure. There is no need for
and no use in giving LMWH in the
interim. He further stated that switching
from warfarin to rivaroxaban is safe and
effective.
There are low discontinuation rates
with rivaroxaban, with reports of high
patient and doctor satisfaction. The use of
rivaroxaban is effective and safe for acute
and long-term VTE treatment as well as
stroke prevention inAF. Bayer HealthCare
Pharmaceuticals is anticipating the
imminent registration of rivaroxaban for
AF in South Africa.
G Hardy
