SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 7 NUMBER 2 • JUNE 2010
59
Antiplatelet therapy and anticoagulation
Although antiplatelet therapy can have a role in combination
with oral anticoagulation therapy, the ‘routine’ addition of aspirin
to warfarin in patients with stable vascular disease is no longer
recommended because it is associated with excess bleeding risk,
particularly in the elderly, without clear benefit.
28,29
Combination
therapy may be helpful in some patients with prosthetic valves, and
those with unstable cardiovascular disease where the risk:benefit
ratio has to be judged individually.
Inpatientswith acute coronary syndromes, or in those undergoing
coronary angioplasty/stenting, use of dual antiplatelet (aspirin plus
clopidogrel) therapy is now routine. However, dual antiplatelet
therapy itself is inferior to warfarin in stroke prevention,
14
so cannot
be regarded as a satisfactory replacement for AF patients in this
context.
Triple therapy
(aspirin, clopidogrel, and warfarin), although
associated with a moderate increase in bleeding complications, is
sometimes used in these complex scenarios and is currently guided
by consensus opinion, given limited trial data.
29,30
Factors influencing type and duration of combination therapy
include: coronary anatomy, presence of intracoronary stents,
perceived bleeding risk, and CHADS2 score. After an initial period
of triple therapy, stented patients may then be continued on
warfarin plus a single antiplatelet (typically clopidogrel),
2,30
with
some cardiologists continuing this therapy beyond 12 months,
although contemporary guidelines advise warfarin monotherapy in
stable patients beyond this stage.
31
The interventional cardiac centre should be contacted if the
planned thromboprophylaxis strategy is not clear.
Thromboprophylaxis therapies for the future
The benefit of warfarin is reduced, if not lost, when the INR is out
of the therapeutic range for a significant proportion of the time.
Indeed, it confers no advantage over antiplatelet therapy per se
if the INR is out of range for more than 40% of the time.
32
Even
with specialist anticoagulation clinic input, achieving stable INRs
can be challenging. This, together with the multiple food and drug
interactions and the inconvenience of serial retesting, has driven
the development of newer oral antithrombotic agents.
Recently,
dabigatran
– a direct thrombin inhibitor – has been
shown to be as efficacious as warfarin, but with a lower bleeding
risk; furthermore, at a higher dose, it offered superior stroke
prophylaxis with a similar rate of major haemorrhage to warfarin
therapy.
33
Its use does not require monitoring or dose adjustment,
and appears ideal for those who cannot achieve stable INRs on
warfarin. Ultimately, it appears likely that dabigatran and similar
drugs
34
will replace warfarin, which would herald a new era of
anticoagulation and optimal management of thromboembolic
risk.
An obvious non-pharmacological target for reduction of
thromboembolism is the left atrial appendage, given that it is
responsible for more than 90% of thrombi in non-rheumatic
AF.
12
It may be excised or excluded in patients undergoing
cardiac surgery,
35,36
although prospective stroke outcome data
are awaited. Percutaneous appendage closure devices have been
developed recently, which may have much wider application
than surgical techniques and could become an alternative to
oral anticoagulation.
38,39
However, general uptake will depend on
proven long-term efficacy and cost-effectiveness compared with
oral anticoagulation.
Treatment of AF (rate and/or rhythm control)
Acute symptomatic AF
For many cases of AF, relatively stable clinical status at presentation
allows initial management to take place in primary care.
Sudden-onset AF, whether first-presenting or recurrent,
associated with severe symptoms of dizziness, breathlessness, or
palpitation should be considered for management in an acute
secondary care setting. In particular, patients with a ventricular
rate greater than 150 bpm, ongoing chest pain, or signs of
critical hypoperfusion need emergency admission. Those with
life-threatening haemodynamic instability should be treated by
emergency electrical cardioversion. This particularly applies to the
rare but life-threatening condition of pre-excited (broad complex)
AF in the context of Wolff-Parkinson-White (WPW) syndrome –
an irregular broad complex tachycardia, which may be the first
presentation of some WPW patients.
If the patient can be stabilised by medical therapy (including
acute rate control), consideration is then given to duration of AF:
Greater than 48 hours or uncertain, the strategy should be
•
anticoagulation and rate control in the first instance, with a
view to cardioversion after
>
3 weeks at therapeutic INR (target
2.5)
Less than 48 hours, attempts to restore sinus rhythm (typically
•
intravenous flecainide if no structural heart disease, amiodarone
otherwise) can be made.
Rate control
Drugs achieve control of the ventricular rate during AF by acting on
the atrioventricular (AV) node to reduce the number of impulses
that get through. Ideally, rate-controlling agents should control the
heart rate both at rest and during activity in a graded manner, as
is the physiological norm in sinus rhythm. Although such an ideal
does not exist, patients with otherwise good cardiac function may
tolerate this state of ‘rhythm failure’ if excessive rate swings are
prevented.
Although the aim of rate control is primarily to improve
haemodynamic stability and symptoms, it is known that persistently
high rates put some patients at risk of subsequent cardiac failure
– so-called
tachycardia-related cardiomyopathy
. This means that
even asymptomatic patients should have their need for rate control
assessed.
Suggested targets for rate control are a resting heart rate of
60–80 beats/min, and 90–115 on moderate exercise.
2
In the
AFFIRM trial, goals were pre-defined as
<
80 bpm at rest, and
<
110
bpm during a six-minute walk test.
39
In retrospective analysis of the
RACE trial (target
<
100 bpm at rest only) and AFFIRM data,
40
the
primary endpoint of mortality, cardiovascular hospitalisation, and
myocardial infarction did not differ between those who achieved
the rate target and those who did not. Therefore, although
many cardiologists would use the target rate-control guidelines
– particularly in symptomatic patients (before accepting that the
‘rate control strategy’ has failed), it remains uncertain how strict
the goals should be. The ongoing RACE II study,
40
prospectively
comparing ‘strict’ with ‘lenient’ rate control outcomes, may provide
further clarification.
How can rate control be assessed in primary care?
The AFFIRM trial used the six-minute walk test to assess rate control,
while other options include treadmill testing or 24-hour Holter
