CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 3, April 2013
100
AFRICA
Use new antiplatelet therapies consistently in clinical practice
Optimising the benefits of new anti-
platelet therapies in daily clinical
practice should be based on selecting
the particular agents that the responsible
clinician would like to use in managing
acute coronary syndrome (ACS) patients
and then sticking to this selection.
Speaking in Accra, Ghana to African
cardiologists and physicians attending
a special AstraZeneca-sponsored CME
symposium, Prof Jean-Pierre Bassand,
past president of the European Society of
Cardiology and head of Cardiology at the
University of Besancon, Franche-Comte,
noted that ‘In my 35 years of experience in
cardiology, physicians and nurses respond
best when they have a simpler regimen of
anti-coagulation and anti-platelet agents
to use in the ACS setting.’
Aspirin’s position as a rather weak anti-
platelet agent is now open to challenge by
the newer agents, which offer greater and
more consistent platelet inhibition, Prof
Bassand said. ‘The use of clopidogrel
with aspirin in dual anti-platelet therapy
was based on the results of the CURE
and Chinese CCS1 studies, which showed
significant reductions in the traditional
composite endpoints of cardiovascular
death, myocardial infarction (MI) and
stroke. These agents in combination
became the first-line antiplatelet treatment
in ACS to reduce events, and of course in
interventional approaches, to reduce stent
thrombosis.’
Over time and in response to the still
significant mortality and morbidity that
ACS patients are exposed to, new efforts
in anti-platelet innovation focused mainly
on the ADP receptors of platelets, now
referred to as P2Y
12
receptors.
The first agent to be introduced in this
class of P2 Y
12
antagonists was prasugrel,
which showed superiority to clopidogrel
in combination with aspirin, with a 20%
relative risk reduction (RRR) in death, MI
and stroke in the TRITON study, but with
an expected increase in major bleeding
risk. The range of inhibition of platelets
was much greater (75% inhibition)
compared to the 35–40% achieved using
clopidogrel. The benefits of prasugrel
have been shown to be a faster onset of
action with greater and more consistent
platelet inhibition.
‘But the TRITON study used a
niche approach in that prasugrel was
administered in the catheterisation
laboratory toACS patients whose anatomy
was known and who were also clopidogrel
naïve. This has resulted naturally in a
more limited evidence-based guideline
recommendation for prasugrel’s use
internationally’, Prof Bassand said.
The next agent (recently launched in
both Ghana and Mauritius), ticagrelor, is
a new chemical class of P2Y
12
antagonist,
a cyclopentyltriazolo-pyrimidine and not
a thienopyridine pro-drug like clopidogrel
and prasugrel. It does however have a
similar profile to prasugrel with regard to
its onset of action, and achieving greater
inhibition of platelet function with an
increased risk of bleeding.
In the PLATO trial, a major phase III
trial in over 18 000ACS patients, tigacelor
was compared to clopidogrel, both in
combination with aspirin. The primary
endpoint was time to first occurrence of
death from vascular causes, MI or stroke.
At 12 months, the primary endpoint had
occurred in 9.8% of patients receiving
ticagrelor compared to 11.7% of patients
receiving clopidogrel. This treatment
benefit was seen within 30 days and was
maintained over the study period of 12
months. There was also a further 15%
risk reduction in myocardial infarction
rates in patients receiving ticagrelor over
clopidogrel-treated patients.
‘However, what was completely new
in the PLATO study was the statistically
highly significant absolute risk reduction
of 1.1% in cardiovascular mortality in the
ticagrelor-treated patients’, Dr Bassand
said. The explanation for the overall
reduction in cardiovascular death is
uncertain, but may be due to the blocking
of adenosine uptake by cells. ‘Perhaps
the better results are also due to a more
consistent effect of ticagrelor over the
wider base of patients treated in the
PLATO study, which included all-comers
in the ACS, reflecting the spectrum of
patients seen in daily clinical practice.’
‘PLATO also included all ACS patients
whether they had been treated with
clopidogrel or not, and also regardless of
whether the clinician intended to manage
the patient medically, using interventional
or surgical procedures’, Prof Bassand
stressed.
Prof Bassand has been intimately
involved with the development of
ESC guidelines for STEMI (2012) and
non-STEMI (2007 and 2011) management
over the past decade. ‘These guidelines
have incorporated the new agents but not
in a hierarchical manner. The guidelines
include the first-line use of ticagrelor
based on the PLATO study results, noting
its particular value in diabetic and renal-
failure patients.
For prasugrel patients, selection is
needed, as those with a low body weight,
a prior history of stroke and the elderly
(above 75 years) do not derive benefit
and are at higher risk for bleeding’. In
addition, prasugrel should be given in
the catheterisation laboratory only, in
clopidogrel-naïve patients intended for
PCI once their anatomy is known, except
in patients with STEMI intended for
primary PCI in whom prasugrel can be
administered before their anatomy is
known. In medically managed patients,
no superior efficacy over clopidogrel was
shown with prasugrel in the Trilogy
trial. In patients who cannot be given
ticagrelor or prasugrel, clopidogrel
remains a valid option.
Setting his sights on the future, Prof
Bassand noted the need to recognise the
weak anti-platelet action of aspirin and
the developing data based on the WOEST
trial, which has driven a first nail in the
coffin of aspirin use in ACS. ‘While
this study was in only 600 patients and
looks at the use of clopidogrel with a
vitamin K antagonist, compared to triple
therapy with aspirin, clopidogrel and a
vitamin K antagonist in patients with
atrial fibrillation who are already on oral
anticoagulation for thrombosis prevention
and who then undergo PCI stenting, the
results showed no benefit of triple over
dual therapy but a higher risk of bleeding
and death. This may have implications for
aspirin therapy if this information were
confirmed by larger trials in the future.’
J Aalbers
Prof JP Bassand speaking at the
African launch of ticagrelor
‘We may in future have to recommend no
aspirin for ACS patients’, he speculated.
