CLINICAL
THROMBOSIS
THE THROMBOTIC RISK OF
NON-VALVULAR AF
Prof
James Ker
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia that a clinical practioner will have to deal with. The
prevalence of atrial fibrillation increases with increasing age.
AF increases the risk of an
embolic stroke five-fold,
irrespective of whether the AF
is chronic or paroxysmal and
recently it was realised that up
to 30% of cryptogenic strokes
may be caused by AF.
AF also increases the risk of
systemic embolism apart from stroke.
Strokes caused by AF are associated
with about a 50% increased risk of
disability and a 60% increased risk
of death as compared to strokes of
other aetiologies. Strokes related to
AF result from cardio-embolism of a
large cerebral artery and therefore
tend to be larger than other strokes.
However, strokes related to AF are
largely preventable because oral
anticoagulants (OAC) are so effective,
which includes vitamin K antagonists
(VKA) such as warfarin and the newer
non-VKA oral anticoagulants (NOACs)
of which there are two available in SA -
dabigatran and rivaroxaban. The most
important risk factors for non-valvular
stroke are: Prior stroke or transient
ischaemic attack (TIA), increasing
age, hypertension and diabetes
mellitus. Women seem to have a
higher stroke risk.
EFFECT OF ASPIRIN
A meta-analysis of aspirin to reduce
the risk of stroke in AF did not show
any benefit. The relative risk reduction
(RRR) was 19% but the confidence
interval (CI) went from -1 to 35, thus
crossing the ‘1’ line, making the result
non-significant. The bleeding risk of
aspirin was considerable with major
bleeding and intracranial bleeding not
different between OAC and aspirin.
Adverse events occurred more
frequent among very elderly who
were taking aspirin.
EFFECT OF WARFARIN
Stroke or systemic embolism is
significantly reduced by VKA (warfarin):
RRR 64% (CI: 49%-74%) as compared to
placebo or no treatment. The absolute
risk reduction is 2.7% per year which
translates to a number-needed-to-treat
(NNT) of 37 for embolism inpatients
per year with no history of prior stroke
(primary prevention). In patients with
a prior history of stroke (secondary
prevention) warfarin reduced stroke by
absolute reduction of 8.4% with NNT
of only 12, which is highly effective.
Warfarin also significantly reduced
mortality by a RRR of 26% (95% CI:3-
43%) with absolute risk reduction of
1.6% per year, NNT 63.
The problem with warfarin is that
it has a narrow therapeutic index that
necessitates frequent monitoring with
dose adjustments, slow onset of action
and slow decline in effect when drug
is stopped, poor patient adherence and
many food and drug interactions.
EFFECT OF NOACs
A meta-analysis of four phase three
trials comparing the efficacy and
safety of the new oral anticoagulants
with warfarin for stroke prevention in
patients with AF has been published.
There were 42 411 patients receiving
a new oral anticoagulant as compared
to 29 272 patients with AF receiving
warfarin. The underlying risk for stroke
differed significantly between trials
with CHADS2 scores varying from
3-6. Median time of follow-up ranged
from 1.8 years to 2.8 years. Stroke or
systemic embolism were significantly
reduced by NOACs as compared to
warfarin: Pooled effect with a random-
effect model showed a RRR of 19%
(95% CI: 9-27%) by NOACs as compared
to warfarin. Haemorrhagic stroke was
reduce by 51% (95% CI: 36-62%) in the
NOAC group as compared to warfarin.
Intracranial haemorrhage was equally
significantly reduced by NOAC by RRR
52% (95% CI: 41%-61%). Major bleeding
did not show any significant difference.
The NOACs did not significantly reduce
ischaemic strokes as compared to
warfarin. All-cause mortality was also
significantly reduced by NOACs with
RRR