1. Dipyridamole with
or without aspirin
This consensus statement was prepared by Professor
Jan-Edvin Olsson, Linköping, Sweden. The discussion was chaired
by Professor Gudrun Boysen, Copenhagen, Denmark and by Professor
Jan-Edvin Olsson. Professor Hans-Christoph Diener, Essen, Germany
and Professor Charles Warlow were speakers in this session.
The attached document was accepted as a consensus
statement by the Update conference.
1.1.
This consensus statement is provisional, since the European Stroke
Prevention Study 2 (ESPS2) was published shortly before the
meeting and had been read only by a minority among the audience.
1.2.
Awaiting further analysis of the published report of ESPS2 and a
systematic overview of the effect of dipyridamole, a low or medium
dose of aspirin (75-300 mg daily), as mono-therapy, should be the
first choice of antiplatelet treatment for patients with
uncomplicated first ever stroke or TIA.
1.3.
Patients should be informed of the results of ESPS2 and the possibility
of this supplementary preventive treatment.
1.4.
In patients with recurrent ischaemic cerebral events, a dose of 200 mg
dipyridamole twice daily may be added to the aspirin treatment.
1.5.
In patients with aspirin allergy, monotherapy with dipyridamole may be an
alternative to ticlopidine.
2. Ticlopidine
This consensus statement was prepared by Dr Hans-Göran
Hårdemark, Uppsala, Sweden. The discussion was chaired by Dr Hans-Göran Hårdemark, and Professor Rolf Nyberg-Hansen,
Oslo, Norway. Associate Professor Andreas Terent Uppsala, Sweden
and Professor Juha Sivenius, Koupio, Finland, were speakers in
this session,
The attached document was accepted as a consensus
statement by the Update conference.
Update consensus statement, Stockholm, November 1996
2.1.
Ticlopidine is registered in some countries (incl Sweden) for stroke
prevention in patients with intolerance to aspirin. The results of
a large clinical trial of its derivative, clopidogrel, were not
available at the meeting.
2.2.
Ticlopidine, in an oral dose of 250 mg twice daily, is indicated as a
first choice of antiplatelet treatment in patients with peptic
ulcer, history of gastrointestinal bleeding and bronchial asthma
and in patients with intolerance to aspirin for other reasons.
2.3.
Ticlopidine should be an alternative to aspirin or combined
aspirin-dipyridamole in non.-responders to these treatments.
3. Carotid surgery
This consensus statement was prepared by Professor
Christian Blomstrand, Gothenburg, Sweden, and by Associate
Professor Jesper Swedenborg, Stockholm, Sweden. The discussion was
chaired by Professor Christian Blomstrand and Associate Professor
Jesper Swedenborg. Professor Charles Warlow, Edinburgh, Scotland,
and Associate Professor Nils Gunnar Wahlgren, Stockholm, Sweden,
were speakers in this session.
The attached document was accepted as a consensus
statement by the Update conference.
3.1.
Today the only well-documented predictor reflecting the risk of future
stroke in patients with carotid stenosis is the degree of
stenosis. Other risk factors exist but their role in the decision
making for carotid surgery is less well or not at all examined.
3.2.
The two large randomised studies of carotid surgery, the European Carotid
Surgery Trial (ECST), and the North American Carotid
Endarterectomy Trial (NASCET), measure the degree of stenosis from
angiography with slightly different methods. A 70% NASCET stenosis
is approximately equivalent to a 80% ECST stenosis, hereafter
named severe stenosis.
3.3.
From existing data it can be concluded that surgery is of benefit in
patients with a symptomatic severe carotid stenosis, if the rate
of severe surgical complications is below 5%. For low degrees of
stenosis (<30% ECST stenosis), surgery is harmful. For patients
with moderate stenosis (ECST 30-80%), no bene-fit from surgery has
been demonstrated. It is, however possible that patients, at least
in the upper range of stenosis degree in the latter group, with a
certain risk factor profile, may benefit from surgery. Until such
risk factors have been established, either from existing data or
from new randomised studies, operation for moderate stenosis is
not recommended unless clinical indications speak very strongly in
favour of surgery. Risk factors which may be of importance are
presence of cerebral versus retinal ischaemic attacks, minor
stroke versusTIA, presence of infarct on CT, plaque morphology,
flow restriction by the carotid stenosis and presence of
associated disease.
3.4.
Attempts to confirm a diagnosis of suspected symptomatic carotid stenosis
should be urgently started and include history, neurological and
cardiovascular examination and duplex scanning of the carotid
arteries. CT and/or MR investigation should be done at least in
cases with symptoms of cerebral lesions.
3.5.
Patients who are considered for carotid surgery, in general patients with
severe carotid stenosis, should promptly be referred to a team of
co-ordinated expertise including neurologist, vascular surgeon,
internist specialised in cardiovascular medicine and experts in
ultrasonography and radiology. A sufficient volume of experience
in carotid surgery and in neurovascular diagnostics corresponding
to the requirements of ECSTand NASCET centres should be requested
from this team.
3.6.
With respect to timing of surgery it should be kept in mind that the risk
of stroke is highest the first weeks after a qualifying symptom
and gradually falling to a level similar to asympto-matic stenoses
after ½-1 year. Accordingly in all cases with symptomatic carotid
stenosis (TIA, amaurosis fugax or minor stroke), surgery should be
performed as early as possible.
3.7.
Duplex scanning needs validation against angiography in each centre
before decisions about surgery can be made without conventional
angiography. If angiography is used the deg-ree of stenosis should
be clearly stated in per cent according to the ECST method. Since
cerebral angiography carries a small but definite risk of
complications, attempts should be made to adopt and evaluate
alternative non-invasive angiographic techniques like MR or CT
angiography to complement ultrasonographic techniques in patients
who need angiography.
3.8.
Duplex scanning of the carotid artery and check up of all patients by the
neurologist regarding neurological or neuropsychiatric symptoms
should be done pre- and postoperatively. A quality register should
include such data to be valid. Thorough follow-up of vascular risk
factors and treatment of other vascular diseases is of crucial
importance and collaboration between the patients primary doctor
(general practitioner, internist, cardiologist or neurologist) and
the carotid surgery team must be near and firm.
3.9.
The documentation of the usefulness of emergency carotid surgery is weak
and it should be pointed out that the risks are larger in the
early phase after stroke with moderate or severe deficits.
3.10.
Surgery for asymptomatic stenosis has been shown to be of benefit in the
Asymptomatic Carotid Artery Surgery Trial in North America but the
benefit is very small and several questions remain to be answered.
Therefore surgery for asymptoma-tic carotid stenosis is not
recommended unless included in a trial. The Asymptomatic Carotid
Artery Surgical Trial is a large multicenter European Trial which
is presently going on.
3.11.
Angioplasty with or without stenting has no proven value as an alternate
standard method in carotid stenosis and should as yet only be used
within the context of randomised studies. Angioplasty of
intracranial severe stenoses and in proximal aortic arch artery
stenosis should only be performed in highly specialised
neurovascular centers with experienced interventional
neuroradiologist and careful docu-mentation of effects including
complications.
4.
Aspirin and anticoagulants in secondary stroke prevention
This consensus statement was prepared by Associate
Professor Bo Norrving, Lund, Sweden. The discussion was chaired by
Associate Professor Bo Norrving, and Associate Professor Andreas
Terent, Uppsala, Sweden. Associate Professor Andreas Terent and
Professor Gudrun Boysen, Copenhagen, Denmark, were speakers in
this session.
The attached document was accepted as a consensus
statement by the Update conference.
General therapy
4.1.
Aspirin: Besides active risk factor intervention, aspirin should be basic
therapy in the long term secondary prevention after TIA and
ischemic stroke, provided specific therapies are not indicated (see
below). An aspirin dose of 75 mg is recommended as first choice,
and should be continued without any fixed time limit. Aspirin
carries a risk of major or fatal bleeding complications of 0.6%
per year compared to about 0.2% in placebo groups.
4.2.
Anticoagulants: Anticoagulants are not recommended as routine secondary
prevention after cerebral ischemic events in patients with sinus
rhythm, because this therapy has not been shown to be more
effective than aspirin in this setting and carries a higher risk
of bleeding.
Specific
situations
4.3.
Atrial fibrillation, and other well established cardioembolic sources:
Anticoagulants are recommended as first choice in these patients,
provided that there are no contraindications. A target INR
interval of 2.0-3.0 is recommended. Treatment should continue as
long as the arrhythmia persists and no contraindications develop.
In secondary prevention in non-valvular atrial fibrillation
patients, anticoagulants carry a risk of major or fatal bleeding
complications of 2.1%-2.8% per year. As secondary choice, aspirin
in a dose of 300 mg could be used. In patients with mechanical
heart valve prosthesis or mitral valve stenosis, anti-coagulants
are also recommended, aiming at an INR of 3.0 to 4.5. There are no
randomised clinical trials guiding clinical practice in patients
with acute myocardial infarction and embolism to the brain, but
anticoagulants for 3-6 months may be used; further antithrombotic
therapy may be guided from echo-cardiographic findings.
4.4.
New ischemic symptoms during antiplatelet therapy. The
possibility of non-ischemic causes should be considered, and a CT
scan should be done in most instances. Screening tests for large
artery stenosis and cardioembolic sources should be performed (or
repeated if performed earlier). If negative, addition of
dipyridamol to aspirin is recommended. A switch to ticlopidine is
an alternative. The prognostic significance of new TIAs during
antithrombotic therapy is unknown.
5. Aspirin and
anticoagulants in acute stroke
This consensus statement was prepared by Associate
Professor Bo Norrving, Lund, Sweden. The discussion was chaired by
Associate Professor Mona Britton, Stockholm, Sweden and by
Associate Professor Carl-Erik Söderström, Stockholm, Sweden. Dr
Peter Sandercock, Edinburgh, Scotland, and Dr Trond Dahl, Oslo,
Norway, were speakers in this session.
The attached document was accepted as a consensus
statement by the Update conference.
General therapy
5.1.
Aspirin: The role of antiplatelet therapy in acute stroke is unclear at
present. However, the value of aspirin for secondary prevention of
stroke following TIA or minor ischemic stroke has been clearly
established, and it is highly probable that the relative risk
reduction of aspirin is similar in the acute phase. Interim
results from two major trials, IST and CAST, are consistent with
this view, and show that early treatment is not associated with
any major bleeding hazard. However, final results from these two
trials are not yet available.
5.2.
Heparin: From a systematic review, anticoagulants highly significantly
reduces the risk of deep venous thrombosis, whereas the effect on
other outcomes is unclear. Although the benefits and risks of
heparin use in acute stroke is not yet clarified, a low dose of
heparin is often used in patients with immobility or leg paresis
(patient groups with the highest risk of these complications),
after a CT scan has excluded intracerebral haemorrhage. From a
pharmaco-logical point of view, low molecular heparin appears more
logical to use than unfractionated heparin, but there is as yet no
trial evidence on this issue. High dose unfractionated heparin is
associated with an increased bleeding risk and should not be used.
Specific situations
5.3.
Atrial fibrillation: Anticoagulants are well established as secondary
prevention in patients with atrial fibrillation, but the benefit
and risks of treatment start in the acute phase is unknown. It
seems advisable to perform a CT scan after 4-8 days and start with
oral anticoagulants if CT does not show any bleeding. Similar
guidelines may be applied for patients with other well established
cardioembolic sources (such as acute myocardial infarction, mitral
valve stenosis, thrombus in the left atrium or ventricle, and
dilated cardiomyo-pathy).
Early
(immediate) heparin and oral anticoagulant therapy is by tradition
sometimes started in patients with TIA or minor stroke and no
contraindications for long term treatment, provided that a CT scan
has excluded haemorrhage.
5.4.
Progressive ischemic stroke: The pathophysiology of progressive stroke is
largely unknown. The value of antithrombotic therapy has not been
established from clinical trials but is widely used clinically.
Heparin therapy is often used on an individual basis for 4-5 days,
provided that the symptoms are not already severe, and that
thromboembolism (and not systemic and other causes) are thought to
be the most likely cause of the worsening.
5.5.
Severe large artery stenosis: These patients are thought to carry a high
risk of early re-embolisation, but this has not been clearly
established, nor has the most effective antithrombotic therapy in
the acute phase. Until supported by more data, on an individual
basis heparin therapy may be used in patients with severe (>70
%) large artery stenosis presenting with TIA or minor ischemic
stroke.
6. Thrombolysis
This consensus statement was prepared by Associate
Professor Nils Gunnar Wahlgren, Stockholm, Sweden. The discussion
was chaired by Professor Werner Hacke, Heidelberg, Germany and by
Dr Vasilios Kostulas, Huddinge, Sweden. Professor Werner Hacke, Dr
Christian Carlström, Stockholm, Sweden and Professor Livia
Candelise,Milan, Italy, were speakers in this session.
The attached document was accepted as a consensus
statement by the Update conference.
6.1.
Thrombolytic therapy using 0.9 mg of tPA within 3 hours after onset
of symptoms, is the only medical therapy for stroke proven
efficacious. However, intravenous thrombolysis cannot currently be
recommended for use in an unselected population of acute ischaemic
stroke patients.
6.2.
It is recommended to include acute stroke patients in placebo-controlled
trials with tPA, even if the delay between onset of symptoms and
treatment is less than 3 hours, since the number of patients in
randomised t-PA trials still is limited.
6.3.
Although inclusion in clinical trials should be the first choice, active
tPA treatment within a strict quality control protocol
demonstrating a low complication rate may be justified after
informed consent within 3 hours after onset of neurological
symptoms in centers with expertise in neurological evaluation of
stroke patients, and in evaluation of early infarct signs on CT.
Unrestricted use of active tPA in centres without sufficient
expertise should be strongly discouraged.
6.4.
Streptokinase, or other thrombolytic agents with unproven efficacy and
safety in acute stroke, should not be used in acute stroke, except
within clinical trial settings.
6.5.
The need of extended randomised trials of thrombolysis in acute stroke
was generally acknowledged.