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----- Original Message ----- 
From: "Charles Brault" <[EMAIL PROTECTED]>
To: "URG-L Mailing List" <[EMAIL PROTECTED]>
Sent: Friday, August 22, 2003 1:34 AM
Subject: URG-L: Angioplastie est sup�rieure � la thrombolyse !




Evidence builds for transfer PCI, with potential role for
thrombolysis: DANAMI-2 and SIAM III

Boston, MA and Bethesda, MD - Results of the DANAMI-2 trial, showing
a strategy of transfer PCI to be superior to thrombolytics for AMI,
have now been published in the August 21, 2003 issue of the New
England Journal of Medicine.[1] Meanwhile, the SIAM III study,
appearing this week in the August 20, 2003 issue of the Journal of
the American College of Cardiology, suggests that transferring
patients for immediate stenting following thrombolysis at a community
hospital reduces cardiac events, compared with a conservative
approach of delayed elective stenting.[2]

An editorial accompanying DANAMI-2 says it is time to rethink the
logistics of emergency care such that AMI patients are taken not to
the closest hospital but to the closest center with primary
angioplasty. Others say a facilitated PCI approach will likely win
out in the end, regardless of where a patient first arrives with an
MI.

DANAMI-2: applicable results

The Danish Multicenter Randomized Study on Fibrinolytic Therapy
versus Acute Coronary Angioplasty in AMI 2 (DANAMI-2) results were
first presented at the 2002 American College of Cardiology meeting,
as reported by heartwire. Lead investigator Dr Henning R Andersen
(Aarhus University Hospital, Denmark) also presented intermediate
results at the XIVth World Congress of Cardiology in May 2002. In the
interim, results from the PRAGUE 2 study, conducted throughout the
Czech Republic, were reported at the 2002 European Society of
Cardiology meeting, reaffirming the DANAMI-2 results.

DANAMI-2 results
A total of 1572 AMI patients participated in the DANAMI 2 trial and
were randomized to either intravenous alteplase or primary
angioplasty; 1129 patients were enrolled at referral hospitals and
443 patients were enrolled at five invasive-treatment centers.
"In a large cohort, we found that primary angioplasty is superior to
fibrinolysis for patients who have myocardial infarction with
ST-segment elevation, even when patients are admitted to a local
hospital without angioplasty capabilities and must be transported to
an invasive-treatment center," the investigators write.
Among patients randomized to angioplasty from a referral hospital,
8.5% died, had clinical evidence of reinfarction, or had a disabling
strokethe primary composite end point of the studywithin 30 days of
the initial AMI. By contrast, the primary end point was reached by
14.2% of patients randomized to thrombolysis at a referral hospital.
These results were comparable to those of patients randomized at
invasive-treatment centers.
"The superiority of angioplasty over fibrinolysis was driven by a 75%
reduction in the relative risk of clinical reinfarction, whereas the
reduction in the risks of death and stroke did not reach statistical
significance," Andersen et al write.
Of note, the median time from the onset of symptoms to randomization
was 135 minutes in the overall population, and the median distance
that patients had to be transported between a referral and invasive
hospital was 50 km (31 miles). A full 96% of patients were
transferred from referral hospitals to invasive-treatment hospitals
within two hours.

One of the most important take-home messages of DANAMI-2, on top of
the primary results of the study, was the sheer feasibility of a
transfer PTCA strategy in a country with almost no angioplasty
expertise before the trial. The five invasive-treatment hospitals had
limited experience in performing primary angioplasty at the beginning
of the study. Moreover, ambulance transfer time did not in itself add
significantly to the overall delay between time of symptom onset and
start of treatment.

"This fact makes our results applicable to most Western communities
and opens the way for more widespread use of primary angioplasty in
the treatment of patients who have myocardial infarction with
ST-segment elevation," Andersen et al write.

In an editorial accompanying DANAMI-2, Dr Alice K Jacobs (University
Medical Center, Boston, MA) asserts that the time has come "to
discard the practice of transporting patients with AMI to the nearest
hospital and to transport them preferentially to centers of
excellence for primary PCI. . . . Moreover, now is the time for
tertiary hospitals capable of performing primary angioplasty to offer
it 24 hours a day, seven days a week."[3]

She adds that strategies for combined pharmacologic and mechanical
reperfusion "hold promise," but that issues of bleeding risk must be
resolved.

Andersen et al concur, noting, "there has been great interest in
'facilitated' angioplasty involving the use of a reduced dose of a
fibrinolytic drug in combination with more aggressive antithrombotic
treatment before angioplasty," although "trials dealing with such
strategies have not yet provided convincing evidence of their
effectiveness."

INSIGHTS FROM SIAM III

A new addition to the literature on this topic is the Southwest
German Study in Acute MI III (SIAM III), a small German study of 163
AMI patients initially treated with thrombolysis at community
hospitals with no onsite cath-lab facilities. SIAM III randomized
trial participants to either hospital transfer and immediate stenting
within six hours of thrombolysis or delayed, elective stenting
approximately two weeks after AMI.

Dr Bruno Scheller (Universit�t des Saarlands, Homburg/Saar, Germany)
and colleagues compared a primary end point of death, reinfarction,
ischemic events, and target lesion revascularization at six months in
the immediate and delayed stenting groups. Before randomization, all
patients received two 10 MU boluses of reteplase, 30 minutes apart,
250 mg of intravenous aspirin, plus a bolus of 5000 IU heparin
followed by a heparin infusion of 1000 IU/hour.
The authors report that the composite primary end point was
significantly reduced in the immediate stenting group, a result
driven largely by the reduction in ischemic events
(rehospitalizations, unplanned angiography, and intractable angina).
Major bleeding complications were similar between the two groups.
Nineteen patients initially randomized to delayed intervention ended
up undergoing early angiography within five days of thrombolysis due
to electrocardiographic evidence of ischemia.

"In summary, immediate transfer of patients to centers for coronary
angiography and stenting within six hours after thrombolysis for AMI
is safe and improves event-free survival, in particular recurrent
ischemia as well as LV function, compared with elective stenting
later on," Scheller and colleagues write.

In an editorial accompanying Scheller et al's study, Dr Raymond G
McKay (Hartford Hospital, CT) points out that SIAM III "illustrates
many of the problems commonly observed in treating STEMI patients
from the community hospital."[4] These include a
longer-than-recommended time to thrombolysis and time to angiography,
an "unacceptable" incidence of recurrent ischemic events, deaths, and
reinfarction at 30 days in the delayed stenting group, and a
less-than-ideal TIMI flow grade 3 at two weeks in the same patients.
The 8.6% incidence of major bleeding in all patients was also
"unacceptably high," McKay says.

"Apart from these limitations, however, the SIAM III study does
rekindle ongoing interest in the facilitated PCI concept," McKay
concludes. What is needed, he adds, are more data to clarify the
efficacy and safety of the facilitated PCI approach. "Such an
approach is clearly needed for all patients, but particularly for the
STEMI patients presenting to the community hospital without immediate
access to a catheter-based therapy."

Passed the point where benefits outweigh risks

To heartwire, McKay hedged his bets in favor of combined
pharmacologic and interventional therapy, despite questions of
bleeding risk or initial hospital admission.

"I think that the facilitated PCI approach will probably win,
regardless of whether the patient presents to a community hospital or
to a tertiary center with on-site cath lab. From the results of
DANAMI-2 and PRAGUE 2 and the other community hospital studies, it's
clear that patients who present to a community hospital have a
door-to-balloon time that is really going to be excessive. So while
they are waiting for definitive revascularization in the cath lab,
there needs to be an attempt to open the infarcted vessel."

The benefits even extend to patients who report first to an invasive
center, McKay said. "Even in the tertiary hospital setting, I think
the advantages of the adjunctive pharmacotherapy are also quite
apparent. Early reperfusion while waiting to get to the cath lab is
more common with the adjunctive pharmacotherapy, the TIMI 3 flow is
more commonly seen, and the outcomes of the intervention are perhaps
better because of improved visualization and fewer embolic episodes."

He believes bleeding risk, the last major obstacle to facilitated
PCI, is fast becoming a thing of the past. "At this point in the
game, catheter technique has improved with smaller catheters, better
groin closure devices, and lower doses of heparin . . . and I think
there is still more to learn with thrombolytics and GP IIb/IIIa
inhibitors, but I think we've passed the point where the benefit is
outweighing the risk."




1. NEJM August 21st, conclusion

A Comparison of Coronary Angioplasty with Fibrinolytic Therapy in
Acute Myocardial Infarction

"Conclusions A strategy for reperfusion involving the transfer of
patients to an invasive-treatment center for primary angioplasty is
superior to on-site fibrinolysis, provided that the transfer takes
two hours or less."


2. Journal of the American College of Cardiology, August 20th.

Beneficial effects of immediate stenting after thrombolysis in acute
myocardial infarction

Objectives

The Southwest German Interventional Study in Acute Myocardial
Infarction (SIAM III) investigated potentially beneficial effects of
immediate stenting after thrombolysis as opposed to a more
conservative treatment regimen.
Background

Treatment of acute myocardial infarction (AMI) by thrombolysis is
compromised by Thrombolysis In Myocardial Infarction (TIMI) 3 flow
rates of only 60% and high re-occlusion rates of the infarct-related
artery (IRA). Older studies showed no benefit of coronary angioplasty
after thrombolysis compared with thrombolytic therapy alone. This
observation has been challenged by the superiority of primary
stenting over balloon angioplasty in AMI.
Methods

The SIAM III study was a multicenter, randomized, prospective,
controlled trial in patients receiving thrombolysis in AMI (<12 h).
Patients of group I were transferred within 6 h after thrombolysis
for coronary angiography, including stenting of the IRA. Group II
received elective coronary angiography two weeks after thrombolysis
with stenting of the IRA.
Results

A total of 197 patients were randomized, 163 patients fulfilled the
secondary (angiographic) inclusion criteria (82 in group I, 81 in
group II). Immediate stenting was associated with a significant
reduction of the combined end point after six months (ischemic
events, death, reinfarction, target lesion revascularization 25.6%
vs. 50.6%, P = 0.001).
Conclusions

Immediate stenting after thrombolysis leads to a significant
reduction of cardiac events compared with a more conservative
approach including delayed stenting after two weeks.


----------------------------------



Have any systems received questions based on the last paragraph
especially?


A major study of heart attack treatment shows that reaming clogged
arteries with angioplasty is more effective than clearing them with
drugs, a finding likely to intensify debate over the best way to
treat the 1.1 million people who have heart attacks each year.

Angioplasty is so much more effective than clot-busting drugs --
which are used routinely because they can be given anywhere -- that
40% more heart attack patients would survive and avoid major
complications if they could obtain the procedure within an hour and a
half, the research shows.

The Danish study, in today's New England Journal of Medicine, is the
latest to prompt U.S. doctors and health-care providers to rethink
how they supply emergency heart attack care. Most U.S. hospitals
don't provide emergency angioplasties because the procedure requires
additional equipment and staff. The USA, unlike Denmark, doesn't have
a national health system designed to rush patients to hospitals that
perform emergency angioplasties. As a result, doctors are reluctant
to risk delaying crucial treatment.

''The time of transport is absolutely critical,'' says Sidney Smith,
professor of cardiology at The University of North Carolina-Chapel
Hill, who adds that the study provides an ''excellent demonstration
of how a rapid transport system and hospitals working together can
achieve good results.''

The Danish researchers compared the two heart attack treatments in
1,129 patients. They found that 14% of patients treated with
clot-busters died or had another heart attack or stroke. Only 8% of
those treated with angioplasty had major complications. That may be
difficult to achieve in the USA, where the average ''door to balloon
time'' -- the time it takes to get a patient from home into the
angioplasty suite -- is about three hours. In the Danish study, the
time was half that.

Smith says heart specialists, hospitals and ambulance services are
discussing setting up a regional heart attack treatment network.
''There's a real opportunity for progress,'' he says.


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