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ClOpidogrel and Metoprolol in Myocardial Infarction Trial |
REACTIONS FROM INDEPENDENT HEART SPECIALISTS TO
COMMIT/CCS-2
Comment by Professor Jean-Pierre Bassand,
Besançon, France, immediate Past-President of the European
Society of Cardiology (ESC).
This is landmark study for several reasons. With
45,852 patients it is the second largest ever carried out in
cardiology. It was organised, run and completed in China thanks
to an exemplary collaboration between the Chinese cardiology
community and Oxford University CTSU.
The findings provide evidence that this dual
platelet inhibition (clopidogrel plus aspirin) results in a
significant reduction of the risk of death and major adverse
cardiac events in patients with acute myocardial infarction,
without excess risk of bleeding. For the first time since GUSTO
(published in 1993), a significant improvement in outcome is
achieved thanks to improved pharmacological treatment in ST
elevation MI. The fact that, in this trial, early use of
metoprolol leads to significant reduction in ventricular
fibrillation and recurrence of MI at the expense of an increased
risk of cardiogenic shock has to be interpreted with
caution.
These two major findings may well prompt us to
launch a revision of the European Society of Cardiology's
Guidelines on the management of this disease.
Dr Nicholas Brooks, President-elect, British
Cardiac Society
The results of this massive trial should prompt an
early revision of guidelines in the United Kingdom where
thrombolytic therapy, rather than the 'gold-standard' of primary
angioplasty is still the most widely used treatment for acute ST
segment elevation myocardial infarction. The incremental benefit
of clopidogrel, added to current anti-thrombotic regimens, is
relatively modest. However the cost of treatment, for up to four
weeks, is also modest and the number of lives saved and
re-infarctions and strokes prevented would fall well within the
limits generally approved by health economists.
The conclusions from the metoprolol arm, though
negative in terms of mortality, are also very helpful against the
existing uncertainty over the value of early intravenous
beta-blockade in the thrombolytic era. Routine consideration of
early intravenous therapy, widely recommended but rarely
implemented, can be withdrawn from the guidelines; oral treatment
should be started when the patient is stable.
The trialists deserve great credit for clarifying
two aspects of the standard of care for patients with acute
myocardial infarction. For once the results of a trial have
answered as many questions as they have posed.
Dr Christopher Cannon, Professor of Medicine,
Harvard Medical School, USA.
Speaking of the findings on metoprolol:
"In this era of increased attention on drug safety, this landmark trial shows that a class of drugs widely thought to be safe and highly effective can have adverse effects in some patients, while being very beneficial in others. It reaffirms the need for doctors to balance the risks and benefits of all medical therapies in individual patients."
"In this era of increased attention on drug safety, this landmark trial shows that a class of drugs widely thought to be safe and highly effective can have adverse effects in some patients, while being very beneficial in others. It reaffirms the need for doctors to balance the risks and benefits of all medical therapies in individual patients."
Dr Michael Gent, former Professor of Clinical
Epidemiology, McMaster University, Hamilton, Ontario, Canada, and
principal investigator in the first large trial of clopidogrel
(CAPRIE).
Speaking of the findings on clopidogrel:
"This is a terrific result. Is this an advance in the treatment of heart attack? Absolutely. The research team has clearly demonstrated a very important benefit. There is no doubt now that a combination of aspirin and clopidogrel should become standard practice straightaway in the emergency treatment of acute MI unless there is a particular reason why not in an individual patient. The one concern - that the combination of aspirin and clopidogrel might cause bleeding - has been shown not to be a problem and it is also clear from the uniformly consistent results that the benefits have to be cost effective."
"This is a terrific result. Is this an advance in the treatment of heart attack? Absolutely. The research team has clearly demonstrated a very important benefit. There is no doubt now that a combination of aspirin and clopidogrel should become standard practice straightaway in the emergency treatment of acute MI unless there is a particular reason why not in an individual patient. The one concern - that the combination of aspirin and clopidogrel might cause bleeding - has been shown not to be a problem and it is also clear from the uniformly consistent results that the benefits have to be cost effective."
Dr Salim Yusuf, Professor of Medicine, Director
of Population Health Research Institute, McMaster University,
Hamilton, Ontario, Canada.
"The results of COMMIT emphasise yet again the
importance of large well-conducted randomised trials. Although
the impact of Clopidogrel appears modest, it is clinically
important and likely highly cost efficient, especially since it
has few side effects. The COMMIT trial also clarifies the
appropriate patient selection for the use of beta-blockers. Both
results are of significant importance for the clinician looking
after patients with heart attacks."
Professor Peter Weissberg, Head of Medical
Information at the British Heart Foundation (BHF).
"This is the most recent of several studies that
have shown that the antiplatelet drug clopidogrel has benefits
for patients with vascular disease. Its use is already well
established for patients with unstable angina and this study
confirms that it is safe and effective also in heart
attacks.
"The findings on metoprolol, a commonly used beta blocking drug, are not altogether unexpected and simply serve to emphasise that, despite their well established benefits after recovery from a heart attack, such drugs should be used with caution in the early hours of an attack."
Comment by Prof. Run-Lin Gao, President of Chinese Cardiology Society:
"This is certainly the largest randomised trial ever conducted in China of treatment for heart disease, with excellent quality data and extremely important new findings. The study provided reliable evidence about the beneficial effects of adding clopidogrel to aspirin and other current standard therapies in acute MI, with very good safety profile. For the first time in over 10 years, a significant improvement in patient survival is achieved with a simple and practicable medical treatment in major heart attack. The study also helped to clarify substantial uncertainties regarding the appropriate use of early beta-blocker in acute MI, emphasizing yet again the importance of large randomised trials. The findings from this study, if implemented widely, would make a significant contribution to the hospital care of acute MI not only in China but also in other populations. We would like to congratulate the joint Fuwai-Oxford research team on accomplishing this landmark study."