CARDIOVASCULAR JOURNAL OF AFRICA • Vol 21, No 6, November/December 2010
344
AFRICA
Myocardial salvage after myocardial infarction depends on early
therapy
In a thought-provoking session on triple
anti-platelet therapy in acute coronary
syndromes, Prof Marco Valgimigli,
Ferrara, Italy, argued that the effect of
clopidogrel is negligible if given too
late to ST-segment elevation myocardial
infarction (STEMI) patients. ‘Clopidogrel
is not fully absorbed during STEMI.
This impaired bio-availability of both the
active and inactive metabolite,
1
combined
with late administration of clopidogrel,
results in minimal anti-platelet inhibition.
In fact, there is limited clinical evidence
supporting the upstream use of clopidog-
rel’, he said.
Referring to the BRAVE 3 study of
abciximab which, when added to aspi-
rin and clopidogrel in STEMI patients,
showed a negligible effect in further
reducing infarct size and mortality. Prof
Valgimigli ascribed this also to late
delivery of the study drug. This negative
outcome was interpreted by the BRAVE 3
study investigators that abciximab should
not be given to STEMI patients in the
catheterisation laboratory.
‘In my view this is not the correct
interpretation’, said Prof Valgimigli. ‘The
problem was that the study drug was
given after four hours to more than 50%
of patients, and time from symptom onset
to PCI was more than five hours in over
50% of the patients. If you consider the
relationship between time-to-treatment
reperfusion and the extent of myocardial
salvage,
2
this is not linear. While early
reperfusion within at least four hours
results in a large reduction in mortality
following significant myocardial salvage,
later intervention results in a much
reduced mortality reduction. Therefore
the overall lack of benefit from abcixi-
mab in Brave 3 is due to treatment and
reperfusion delay.’
Using Medical Research Institute
(MRI) studies
3
of STEMI patients strati-
fied by delay of treatment, Prof Valgimigli
pointed out that the area of potential
myocardial salvage is largest if time to
reperfusion is short and within one to
two hours post infarct. Therefore GIIb/
IIIa agents are of very significant value
if given early.
The evidence for early administra-
tion of anti-platelet agents has been well
shown in the ON-TIME-2 trial
2
of very
early upstream bolus tirofiban treatment.
At the time of arrival at the PCI centre,
patients treated with tirofiban on top of
aspirin and clopidogrel had significantly
lower residual ST-segment deviation than
those receiving only aspirin and clopidog-
rel. The one-year survival rate of those
patients receiving tirofiban within 75
minutes after diagnosis and primary PCI
was 60% lower than those receiving dual
anti-platelet therapy.
Is this time-delay concept the same for
other anti-platelet agents such as clopi-
dogrel? ‘The answer is yes.
4
If clopi-
dogrel is given within six hours there is
a significant benefit on death, re-MI or
stroke in patients undergoing primary
PCI, which disappears if clopidogrel is
given more than 12 hours after diagnosis’,
Prof Valgimigli said.
Is there benefit from using GIIb/IIIa in
non-STEMI patients? ‘In a recent meta-
analysis of 14 RCTs, including 3 424
patients,
5
of tirofiban on top of clopidog-
rel, and aspirin versus clopidogrel plus
aspirin, tirofiban reduced death/MI in the
30 days post-intervention, with an NNT
of 16 to save one life or prevent one MI.’
If one looks at the background therapy
and asks if clopidogrel is improving the
effect of tirofiban, the answer is appar-
ently negative.
5
‘Overall, the explanation for the added
value of GIIb/IIIa might lie within the
multiple other pathways of platelet activa-
tion which still function in the presence
of aspirin and clopidogrel – the platelet
aggregation inhibitor action of the GIIb/
IIIas is therefore a necessary and useful
action’, Prof Valgimigli concluded.
J Aalbers, Special Assignments Editor
1. Heestermans AA, van Werkum JW, Taubert
D. Impaired bioavailability of clopidogrel
in patients with a ST-segment elevation
myocardial infarction.
Thrombosis Res
2008;
122
(6): 776–781.
2. Gersh BJ, Stone GW, White HD, Holmes DR
Jr. Pharmacological facilitation of primary
percutaneous coronary intervention for acute
myocardial infarction: is the slope of the
curve the shape of the future?
J Am Med
Assoc
2005;
293
(8): 979–986.
3. Ripa RS, Nilsson JC, Wang Y,
et al
. Short-
and long-term changes in MI function
morphology, edema and infarct mass after
ST-segment elevation myocardial infarction
evaluated by serial magnetic resonance imag-
ing.
Am Heart J
2007;
154
(5): 929–936.
4. Chen ZM,
et al
. Oral presentation, ACC
2005.
5. Valgimigli M, Biondi-Zoccai G, Tebaldi M,
van’t Hof AW, Campo G, Hamm C,
et al
.
Tirofiban as adjunctive therapy for acute
coronary syndromes and percutaneous coro-
nary intervention: a meta-analysis of rand-
omized trials.
Eur Heart J
2010;
31
(1):
35–49. E-pub 2009 Sep 14.
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