Q |
What are the main results from COMMIT/CCS-2 for
clopidogrel? |
A |
Adding 75mg daily of oral clopidogrel to aspirin within 24
hours of the onset of a heart attack significantly reduced the
relative risk of death in hospital by 7% and the risk of death,
repeat heart attack or stroke by about 10%, without any
significant increase in serious bleeding. These benefits were
additional to standard heart attack treatments, and were seen
even in older patients and those presenting many hours after the
onset of symptoms (who do not typically receive “clot
busting” fibrinolytic therapy). |
Q |
What are the main implications of the clopidogrel
results? |
A |
On average, adding clopidogrel to current therapies benefits
one in every 100 heart attack patients. So, for every million
patients having a heart attack, giving this simple additional
treatment for about two weeks would save 5,000 lives and prevent
another 5,000 repeat heart attacks or strokes. As there are about
10 million heart attacks in the world every year, the findings
from this study – if implemented appropriately widely
– would make an important contribution to saving lives and
reducing disability. |
Q |
What has COMMIT/CCS-2 told us that we did not know
before? |
A |
The use of aspirin for the emergency treatment of heart
attacks had been shown previously in ISIS-2 (Second International
Study of Infarct Survival) to reduce the risk of death and repeat
heart attacks by about one quarter. As a consequence of that
research, which was also conducted by our team, aspirin is now
used routinely during a heart attack (and is then continued
long-term). Aspirin and clopidogrel are anti-platelet drugs that
work through different pathways. COMMIT/CCS-2 has now shown that
blocking both of these pathways with the combination of aspirin
and clopidogrel is even more effective at preventing death and
repeat heart attacks than using aspirin alone. |
Q |
Both aspirin and clopidogrel are anti-platelet
drugs. Is their combination safe? |
A |
The major concern related to any anti-platelet drug is
bleeding, but the study showed that adding clopidogrel to aspirin
for a few weeks in hospital is remarkably safe. There was a small
increase in the risk of minor bleeding and bruising. But, this
large study did not find any material increase in the risks of
haemorrhagic stroke or other serious bleeding (i.e. fatal or
transfused bleed) with the use of clopidogrel in this
setting. |
Q |
How important do you rate the findings? |
A |
Very important. These new findings show that clopidogrel
should now be considered routinely for a wide range of patients
admitted to hospital with suspected heart attacks (largely
irrespective of their age, other characteristics, or the use of
other treatments). |
Q |
Are these results for clopidogrel definitive? |
A |
The large numbers of deaths and relevant non-fatal events on
which these results are based make the findings extremely
reliable and definitive. |
Q |
Were the COMMIT/CCS-2 clopidogrel results in line
with what you expected? |
A |
Adding clopidogrel to aspirin had previously been shown to
reduce the risk of heart attacks in people who had unstable
angina or were undergoing percutaneous coronary intervention
(PCI) balloon angioplasty or stenting. So, although the use of
clopidogrel as an emergency treatment for heart attacks had not
previously been extensively studied, it was reasonable to hope
that it might add to the benefits produced by aspirin. |
Q |
Were there any disappointments with the clopidogrel
findings? |
A |
No – these results are good news for people who are
having a heart attack. |
Q |
Were there any differences between the findings for
clopidogrel in men and women or in different age groups? |
A |
No. The efficacy and safety findings for clopidogrel were
consistent in men and women, and at different ages (including
even among the large numbers of participants aged over 70 who are
quite often not well represented in such studies). |
Q |
Were there any differences between the findings for
patients with heart attacks of differing severity? |
A |
No. Again, the findings for clopidogrel were generally
consistent between patients presenting at different levels of
risk (including those who presented with heart failure). |
Q |
Did the results reveal any types of patients that
are definitely not suitable for clopidogrel? |
A |
Patients who were thought to be at increased risk of bleeding
because they had active bleeding or a history of a bleeding
disorder were excluded from the study. Among the patients
included in the study, however, no particular group could be
identified who would not benefit from clopidogrel. |
Q |
COMMIT/CCS-2 was looking at short-term treatment in
hospital. Do the findings tell us anything about longer-term use
of these drugs? |
A |
The addition of clopidogrel to aspirin for the long-term
treatment of unstable angina has previously been shown to prevent
heart attacks in that setting, and the present COMMIT/CCS-2
results reinforce this evidence. Aspirin is currently used
long-term after heart attacks and ischaemic strokes, and studies
are ongoing to determine whether the addition of clopidogrel
would safely produce greater reductions in the risks of further
heart attacks and strokes. |
Q |
Given the size of this study, are any further
studies of clopidogrel necessary? |
A |
COMMIT/CCS-2 provides clear evidence about the benefits and
safety of adding clopidogrel to aspirin during and just after a
heart attack, which complements the available evidence about the
long-term use of this combination in unstable angina and during
coronary artery procedures. Further studies about the long-term
use of adding clopidogrel to aspirin after heart attacks and
strokes, as well as in other situations associated with high
risks of occlusive vascular events, are still needed. |
Q |
Were you concerned about possible interactions
between clopidogrel and other drugs used by patients having heart
attacks? |
A |
The doctors of patients in the study were free to use any
other treatments in hospital that they considered necessary. In
particular, all of the patients were given daily aspirin, about
two-thirds received anticoagulants (typically heparin) and about
half received fibrinolytic drugs. There was no evidence that the
risks of serious bleeding with clopidogrel were materially
increased in the presence of these other treatments that affect
blood clotting. Nor was there any evidence that the reductions in
the risks of repeat heart attacks or death with clopidogrel were
materially influenced by the use of these or any other treatments
(including the other study drug, metoprolol). That is, the
benefits of clopidogrel appeared to be additional to those of all
of the other current standard treatments used during a heart
attack, without any particular safety concerns. |
Q |
Do you think the dosage of clopidogrel used in
COMMIT/CCS-2 was optimal? |
A |
The daily dose of 75 mg clopidogrel studied has been shown to
produce anti-platelet effects within a few hours and to achieve
maximal anti-platelet effects within a few days. Significant
benefits emerged with this clopidogrel regimen during days 0-1
(i.e. an average of 36 hours) of treatment in COMMIT/CCS-2, which
indicates that it was effective early after initiation. A loading
dose of 300mg clopidogrel could be used to produce maximal
anti-platelet effects more rapidly, but may cause more
bleeding. |
Q |
Are the findings from this study in China
applicable to other populations? |
A |
Yes. There is no evidence that the nature of heart attacks is
materially different in China than elsewhere, or that Chinese
patients react differently to clopidogrel than do other
populations. Furthermore, the concomitant therapies used in
hospital in the study were very similar to those typically used
in other countries. |
Q |
Previous studies have already shown that
clopidogrel is effective in treating heart disease. How could you
justify using placebo? |
A |
Adding clopidogrel to aspirin had previously been shown to be
beneficial for people who had unstable angina or were undergoing
angioplasty or stenting. Before the results of COMMIT/CCS-2
became available, however, there was no good evidence for the use
of clopidogrel during a heart attack. Moreover, entry to the
study was guided by the “uncertainty principle”: that
is, each patient was eligible for inclusion in the study only
when their responsible doctors were substantially uncertain as to
whether clopidogrel was clearly indicated or clearly
contraindicated. |
Q |
Are these results for clopidogrel likely to be
applicable to any other type of anti-platelet drug? |
A |
COMMIT/CCS-2 shows that blocking platelet function in more
than one way can safely produce greater reductions in serious
vascular events. But, these efficacy and safety results for this
particular combination of clopidogrel and aspirin cannot
necessarily be extrapolated to other anti-platelet drug
combinations. |
Q |
Is clopidogrel expensive? Will this treatment be
affordable in less developed countries as well as in more
developed countries? |
A |
Clopidogrel currently costs about US$2-4 per 75 mg daily
dose. But, since the regimen studied in COMMIT/CCS-2 lasted an
average of only about 2 weeks, it is likely to be affordable for
most patients – even in less well developed countries. |
Q |
Are you going to follow the patients long-term to
assess outcomes, or is day of discharge from hospital the final
outcome? |
A |
The study aimed to assess outcome during the scheduled
treatment period of 4 weeks or prior hospital discharge, and
there is currently no plan to follow patients longer-term. |
Q |
The findings on clopidogrel seem clear – that
is, that it saves lives and prevents repeat heart attacks. What
is the most important 'take home' message for doctors? |
A |
Immediate use of 75 mg daily clopidogrel in addition to
aspirin should be considered routinely for all patients
presenting with a suspected heart attack regardless of their sex,
age and the use of other standard treatments (including
fibrinolytic therapy or anticoagulants), unless there is some
clear contraindication (such as a particularly high risk of
bleeding). |