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Emergency clopidogrel could save thousands of
lives worldwide - findings from 46,000-patient heart attack
trial
But caution needed with metoprolol early after
heart attack
Orlando Adding the
anti-platelet drug clopidogrel to aspirin for the emergency
treatment of heart attacks could save thousands of lives a year
worldwide and prevent thousands of repeat heart attacks and
strokes, according to new research presented today (Wednesday 9
March) at the American College of Cardiology annual
conference.
The study also established that giving the
beta-blocker metoprolol as an emergency treatment for heart
attacks cuts the risks of repeat heart attacks and of ventricular
fibrillation.1 But, early use of beta-blocker
treatment raises the risk of cardiac shock in the immediate
aftermath of a heart attack, and these early benefits and hazards
tend to cancel each other out.
The findings are from the 45,852-patient
COMMIT/CCS-2 randomised study2 - the largest ever
conducted in China and the second largest study of emergency
heart attack treatment in the world. This five-year joint
Chinese/British venture involving 1,250 hospitals was organised
by the Fuwai Hospital, Chinese Academy of Medical Sciences,
Beijing, China, and the Clinical Trial Service Unit (CTSU) of
Oxford University, UK.
Aspirin and clopidogrel are anti-platelet drugs
that prevent blood clots through different mechanisms. The use of
aspirin for the emergency treatment of heart attacks had been
shown previously to reduce the risk of death and repeat heart
attacks by about one quarter. The objective of COMMIT/CCS-2 was
to see whether adding clopidogrel to aspirin might be even more
beneficial than aspirin alone.
Beta-blockers are proven effective long-term
treatment in the years after a heart attack. But, their value as
emergency treatment is uncertain and such use is limited,
although current guidelines advise prompt administration unless
there are contraindications. COMMIT/CCS-2 aimed to establish
whether using intravenous then oral metoprolol during a heart
attack could cut deaths and reduce the risk of repeat heart
attacks and cardiac arrest.
Dr Zhengming Chen of the CTSU, the study's
principal investigator, told the ACC's 54th Annual Scientific
Session in Orlando, Florida, that adding 75 mg of oral
clopidogrel daily to aspirin 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 bleeds. These benefits were additional to
those of standard heart attack treatments, and were seen even in
older patients and those presenting several hours after the onset
of symptoms (who do not typically receive "clot busting"
fibrinolytic therapy for their heart attack).
He said: "This means that, on average, adding
clopidogrel to current therapies benefits one out of every 100
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 an estimated 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."
Professor Rory Collins, co-chair of the study's
steering committee and co-director of the CTSU, told the
conference that giving three intravenous doses of 5 mg metoprolol
during a heart attack, followed by 200 mg daily oral doses in
hospital, reduced the relative risk of repeat heart attacks and
ventricular fibrillation by 15-20%, but increased the relative
risk of cardiac shock by about 30% (chiefly during the first day
or so of treatment). In absolute terms, the overall balance of
these different effects was about even, and there was no clear
reduction in hospital mortality for any particular type of
patient.
He emphasised that there was already compelling
evidence that long-term use of beta-blockers after a heart attack
benefited patients. "Our finding of clear reductions in repeat
heart attacks and ventricular fibrillation reinforces this
evidence," he said. "Early after a heart attack, however, the
benefits and hazards with intravenous then oral metoprolol
counter-balanced each other. So, to maximise the benefits and
minimise any potential hazard, it may generally be prudent to
wait until a heart attack patient's condition has stabilised
before starting beta-blocker therapy."
Professor Liu Lisheng of the Fuwai Hospital,
co-chair of the study's steering committee, emphasised the value
of such international collaboration. "The findings from this
large collaborative study in China should help to improve the
treatment of many millions of people around the world who have
heart attacks each year."
The study's cost of UK£1.6 million (US$3
million) was split between the manufacturers of clopidogrel
(Sanofi-Aventis/Bristol-Myers Squibb) and of metoprolol
(AstraZeneca). The British Heart Foundation and UK Medical
Research Council also supported the Oxford coordinating centre.
However, the trial was designed, conducted, analysed, interpreted
and presented by the researchers entirely independently of the
funders.
(ends)
Notes
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