CARDIOVASCULAR JOURNAL OF AFRICA • Vol 23, No 6, July 2012
AFRICA
349
anticoagulation in older patients with AF,
hypertension and CKD.
Warfarin
Warfarin has been the mainstay of
anticoagulation in AF patients. However,
large observational studies have suggested
that compared to placebo, warfarin is
associated with increased risk of both
haemorrhagic and ischaemic stroke in
advanced CKD and is contra-indicated
in stages 4 and 5. Another concern is that
warfarin blocks vitamin K
2
, which may
be important in the prevention of vascular
calcification.
New oral anticoagulants
Prof Rayner continued by discussing
trials in which the new agents were
comparators against warfarin. The RELY
(dabigatran), ROCKET-AF (rivaroxaban)
andARISTOTLE (apixaban) trials showed
that in non-valvular AF, the new agents
were non-inferior or superior to warfarin.
Results from RELY indicated dabigatran
110 mg bid was non-inferior to warfarin,
with 20% fewer major bleeds; whereas
the 150-mg bid dose was superior to
warfarin, although it displayed a similar
rate of major bleeds.
Of note are recent reports of a greater
bleeding risk in the elderly with the use
of dabigatran as opposed to warfarin.
Adverse drug reactions reported to the
Federal Drug Administration suggest
bleeding risk for dabigatran to be higher
(505 cases) than warfarin (176 cases) in
the first quarter of 2012. The RELY study
patients were younger, heavier and with
better kidney function. Rivaroxaban (15 or
20 mg QD) was found to be non-inferior
to warfarin on intention-to-treat analysis
but superior in on-treatment analysis,
displaying a similar rate of major bleeds.
Dabigatran is excreted 80% unchanged
in the urine, with the pharmacokinetics of
dabigatran highly influenced by renal
function. It is currently contra-indicated
in CKD stages 4 and 5 and a dose
reduction is required in CKD stage 3.
Rivaroxaban is excreted one-third
unchanged in the urine, with
concentrations and half-life less
influenced by renal function. Reduction
of the 20-mg rivaroxaban dose to 15
mg is recommended in CKD stage 3,
and it should be used with caution in
stage 4 patients. Rivaroxaban is not
recommended for use in CKD stage 5.
Currently approved registration for the
useof rivaroxaban inadults in theEuropean
Union include the prevention of vascular
thromboembolism in patients undergoing
elective hip- or knee-replacement surgery
(registered for such use in South Africa),
treatment and prevention of recurrent
deep-vein thrombosis and pulmonary
embolism following an acute deep-vein
thrombosis, and prevention of stroke and
systemic embolism in non-valvular AF
patients with another risk factor such as
age or hypertension.
Management of bleeding
complications
Prof Rayner commented on the
management of bleeding complications
in the anticoagulated patient. The next
dose should be delayed or, if appropriate,
treatment should be interrupted.
Individualised bleeding management
may include symptomatic treatment such
as mechanical compression, surgical
intervention and fluid replacement; and
haemodynamic support such as blood
products or blood components. For life-
threatening bleeding, use of specific
procoagulant agents such as prothrombin
complex concentrate (PCC), a PCC
and factor VIIa should be considered;
although there is currently limited clinical
experience with these measures.
Prof Rayner’s concluding statements
were that the new anticoagulants are an
exciting development. The lack of need
for dose monitoring of the new agents
does not however imply a reduction
in haemorrhagic risk. He emphasised
responsible prescribing, the importance
of weighing risk against benefit, and the
importance of understanding the effects
of renal dysfunction on these agents.
Glenda Hardy
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