The putative neuroprotective
effects of antiplatelet compounds and the angiotensin II receptor
antagonist telmisartan were investigated in the Prevention Regimen
for Effectively Avoiding Second Strokes (PRoFESS) trial (Lancet
Neurology 2008; 7:875-884).
Patients who had had an
ischaemic stroke were randomly assigned in a two by two factorial
design to receive either 25 mg aspirin (ASA) and 200 mg
extended-release dipyridamole (ER-DP) twice a day or 75 mg
clopidogrel once a day, and either 80 mg telmisartan or placebo once
per day. The predefined endpoints for this substudy were disability
after a recurrent stroke, assessed with the modified Rankin scale (mRS)
and Barthel index at 3 months, and cognitive function, assessed with
the mini-mental state examination (MMSE) score at 4 weeks after
randomisation and at the penultimate visit. Analysis was by
intention to treat.
There was no significant
difference in the proportion of patients with recurrent stroke with
a good outcome, as measured with the Barthel index, across all
treatment groups. Additionally, there was no significant difference
in the median MMSE scores, the percentage of patients with an MMSE
score of 24 points or less, the percentage of patients with a drop
in MMSE score of 3 points or more between 1 month and the
penultimate visit, and the number of patients with dementia among
the treatment groups. There were no significant differences in the
proportion of patients with cognitive impairment or dementia among
the treatment groups.
The trial concluded that
disability due to recurrent stroke and cognitive decline in patients
with ischaemic stroke were not different between the two
antiplatelet regimens and were not affected by the preventive use of
telmisartan.
What is the link between low
calcium intake in Japan and the risk of stroke? This seems the main
question which a recent study (Stroke.
2008; 39:2449) is trying to investigate.
To investigate the association
between calciumintake and risk of cardiovascular
diseases, a total of 41 526 Japanese men and womenage 40
to 59 years without a history of CVD or cancer and who
had completed a food consumption frequency questionnaire wereenrolled in the study. The subjects were followed up from 1990to 1992 to 2003, and after 533 692 person-years of follow-up,1321 incident cases of stroke (664 ischaemic, 425
intraparenchymalhaemorrhage, and 217 subarachnoid
haemorrhage) and 322 of coronaryheart disease were
documented.
Total calcium intake showed an
inverse associationwith the risk of total stroke. The
study showed that dietary calcium intake was not significantlyassociated with risk of coronary heart disease.
The authors concluded that
dietary calcium intake, especially calciumfrom dairy
products, was found to be associated with a reduced
incidence of stroke among middle-aged Japanese.
To focus on the life style is a
good way to try to prevent stroke and cardiovascular diseases. There
are few studies which proved the correlation between cigarette
smoking and the risk of stroke. However; the effect of smoking
reductionon cardiovascular disease outcomes has not been
studied in Asianpopulations.
In a recent study ( Stroke. 2008;39:2432),
a total of 475 734 Korean men aged 30 to 58 years,
stratified into 9 groups based on smoking status at 2 differenttime points (1990 and 1992), were followed from 1992 to 2001for the occurrence of stroke or myocardial infarction (MI)
events.
Compared with nonreducing heavy
smokers (20 cigarettes/d),those who quit smoking showed
significantly lower risks of ischaemicstroke,
subarachnoid haemorrhage, and MI. For haemorrhagic
stroke, quitters showed lower risk compared with heavy smokers,but the difference was not statistically significant. Compared
with nonreducingheavy smokers, the risks of all stroke
combined and MI amongreducers tended to decrease,
although the reductions were notstatistically
significant. The risks of subarachnoid haemorrhageand MI
in those who reduced from moderate to light smoking tendedto be lower than in nonreducing moderate (10 to 19
cigarettes/d)smokers.
This study concluded that
smoking cessation was associated with a decreasein the
risks of ischaemic stroke, subarachnoid haemorrhage, and
MI.
How safe is carotid stenting as
a potential alternative to carotid endarterectomy in cases of severe
carotid artery stenosis?
Mas J-L et al previously
reported that the rate of any stroke or death within 30 days after
treating the severely stenotic carotid artery surgically was higher
with stenting (angioplasty) than with endarterectomy.
This current study (Lancet
Neurology 2008; 7:885-892) is reporting the results of up to 4 years
of treating carotid artery diseased patients to prevent stroke.
In this follow-up study of a
multicentre, randomised, open, assessor-blinded, non-inferiority
trial, the authors compared outcome after stenting with outcome
after endarterectomy in 527 patients who had carotid stenosis of at
least 60% that had recently become symptomatic. The primary endpoint
of the EVA-3S trial was the rate of any periprocedural stroke or
death (ie, within 30 days after the procedure).
The results of this study suggest that
carotid stenting is as effective as carotid endarterectomy for
middle-term prevention of ipsilateral stroke, but the safety of
carotid stenting needs to be improved before it can be used as
an alternative to carotid endarterectomy in patients with
symptomatic carotid stenosis.
It is important to explore the effects of stroke
in the young population on their ability to return back to work.
This study (Stroke.
2008;39:1526) aimed to
determine the frequency and determinantsof return to
work, in particular the effect of early psychiatric
morbidity, in a population-based study of stroke survivors.
The third Auckland Regional Community Stroke(ARCOS) study was a prospective, population-based, stroke
incidencestudy undertaken in Auckland, New Zealand
during 2002 to 2003.After a baseline assessment early
after stroke, data were collectedon all survivors at 1
and 6 months follow-up.
The results showed that among 1423 patients
registered with first-everstrokes, there were 210
previously in paid employment who survivedto 6 months.
Among those cognitively competent,psychiatric morbidity
at 28 days was a strong independent predictorof not
returning to work.
This study concluded that about half of
previously employed peoplereturn to paid employment
after stroke, with psychiatric morbidityand physical
disability being independent, yet potentially treatable,
determinants of this outcome.
Using the new technologies in stroke
rehabilitation is still under studied especially in stroke in
children. The authors of this study aimed to test whether
contralesional, inhibitory repetitive transcranial magnetic
stimulation (rTMS) could affect interhemispheric inhibition to
improve hand function in chronic subcortical paediatric acute
ischaemic stroke (AIS).
Patients were paired for age and weakness and were randomised within
each pair to sham treatment or inhibitory, low-frequency rTMS over
contralesional motor cortex (20 min, 1200 stimuli) once per day for
8 days. An occupational therapist did standardised tests of hand
function at days 1 (baseline), 5, 10, and 17 (1 week
post-treatment), and the primary outcomes were changes in grip
strength and the Melbourne assessment of upper extremity function (MAUEF)
between baseline and day 10. Patients, parents, and occupational
therapists were blinded to treatment allocation.
The study concluded that contralesional inhibitory rTMS was safe and
feasible for patients with paediatric subcortical AIS, and seemed to
improve hand function in patients with hemiparesis. The authors
mentioned that further studies are required to confirm the potential
role of rTMS in paediatric neurorehabilitation.
Dr.
Amer Jafar writes from the 17th European Stroke Conference, Nice/
France:
In an international press
conference, it was annonuced on the third day of the 17th European
stroke conference (15th May 08) that the European Commission
will invest more than 21 million euros to support central research
into strokes for a period of five years. Dr. Manuel Hallen, head of
health research in the EU, announced the establishment of a
“European Stroke Network” (ESN) with 30 institutional partners from
14 European countries at the XVII. European Stroke Conference in
Nice. The Network is based on two complementary projects in the
field of vascular and cerebral research, namely EUSTROKE (The
European Stroke Research Network) and ARISE (Affording Recovery In
Stroke), which are coordinated by Prof. Stephen Meairs in Mannheim
and Prof. Ulrich Dirnagl in Berlin.
In his presentation in
the press conference Dr Hallen mentioned thatpooling of
competences and resources promotes cooperation and collaboration
amongst European teams, helps to avoid duplication of effort and
increases our chances to make discoveries that can benefit human
health. Research like this will give hope to reduce and eventually
prevent strokes and future suffering of patients and their families.
EUSTROKE aims at improving our understanding of the neurovascular
unit in the brain, which should lead to better prevention and
treatment of stroke. ARISE will investigate a number of novel,
promising therapies, including safer thrombolytics, therapies to
induce repair of lost function, as well as a fast way to selectively
cool the brain. Together, they combine expertise in clinical as well
as pre-clinical stroke research. A common ESN Trial Platform will
help obtain clinical proof of principle and translate research
findings into effective therapy of stroke. For the first time relevant
comorbidities, gender, age and long term outcomes will be
investigated. Services of this advanced ESN Trial Platform, which
will boast over 350 European stroke centers, will be offered to the
European stroke research community.
Johann
Jakob Wepfer Prize 2008 awarded to Marie-Germaine Bousser
The
Johann Jakob Wepfer Prize worth 20,000 euros, which has been
awarded by the ESC Committee since 2005 for outstanding
achievements in clinical work and basic stroke research, was
this year awarded to the French doctor and scientist Professor
Marie-Germaine Bousser, Paris, for her work in the field of
stroke research, especially its genetic and molecular bases in
the early forms encountered in young people. The award is
coupled with the request to present a paper from her work, a
request which she gladly took up with an excellent and as always
highly interesting presentation “about some translations in
vascular neurology”. The laudation was presented by the Dutch
neurologist Prof. Jan van Gijn from the University Medical
Center Utrecht, another outstanding pioneer in stroke research
who captivated the over 2,500 listeners with his wit, charm and
competence.
ESC 14th May
2008
PRoFESS drug Trial:
insignificant results on all fronts
The main event on the second
day of the European Stroke Conference was the announcement of
the results of the long awaited Profess drug trial. The three
lead main investigators of the trial were sharing an hour
presentation at about 11GMT in a fully packed lecture theatre in
the Acropolis in Nice/France. The first speaker was Dr. R,.
Sacco, from University of Miami, Miami, USA. The title of his
presentation was prevention regimen for effectively avoiding
second stroke (Profess) trial: Comparison of a fixed- dose
combination of extended- release dipyridamole ( ER-DP)plus
aspirin (ASA) with clopidogrel. He mentioned that 20,333
patients (mean age 66 years;36% female) were recruited from 695
sites in 35 countries. Median time from ischaemic stroke to
randomisation was 15 days; 39.9% of patients were randomised
within 10 days. He concluded that there is no significant
difference in reducing the risk of recurrent strokes between the
group of ischaemic stroke patients treated with fixed-dose
combination of ASA plus ER-DP (200mg) given twice daily and the
group of stroke patients treated with Clopidogrel alone.
Telmisartan versus
Placebo
Dr. S.
Yusuf from McMaster University in Canada was talking in the
conference about Telmisartan (one of the angiotensin receptor
blocker) and whether it is reducing recurrent strokes in
patients with previous stroke and hypertension. He and his team
compared the telmisartan group of patients with another group
treated for their hypertension with placebo (other drugs but not
telmisartan). Dr Yusuf concluded that there are no significant
differences between the two groups and telmisartan has failed to
show any significant reduction in recurrent stroke in
hypertensive patients comparing to placebo. However, he
confirmed that the potential benefit of telmisartan in treating
hypertension is similar in all type of strokes.
Cognitive and
functional outcomes after stroke
The
last speaker in this session regarding Profess drug trial was
Professor H. Diener from University of Duisburg-Essen, Essen in
Germany. He mentioned that
the Prevention Regimen for Effectively Avoiding Secondary
Strokes (PRoFESS) trial is the largest secondary stroke
prevention trial to date, and investigated whether the
fixed-dose combination of acetylsalicylic acid (ASA) plus
extended-release dipyridamole (ER-DP) compared to clopidogrel,
and telmisartan compared to usual care reduced the risk of
further strokes. Angiotensin II receptor blockers are
neuroprotective in animal models of stroke, and can
theoretically reduce the risk of vascular dementia or severity
of a recurrent stroke. Also there are experimental data to
suggest that dipyridamole may have an effect on cognitive
decline in dementia due to subcortical ischaemia through several
mechanisms including: prevention of new vascular lesions;
anti-oxidant and anti-inflammatory effects; and an increase in
cerebral perfusion. Therefore the effect of telmisartan and ASA
plus ER-DP on both the severity of recurrent stroke, and
cognitive function were assessed.
Patients aged 50 years or older
with an ischaemic stroke within 120 days and who where stable
were included in the trial. A fixed-dose combination of ASA (25
mg) plus ER-DP (200 mg), given twice daily, compared to
once-daily clopidogrel (75 mg), and telmisartan (80 mg once
daily) compared with placebo were investigated using a 2 x 2
factorial study design. Severity of recurrent stroke was
assessed by modified Rankin. Cognitive function was assessed by
serial changes in Mini Mental State Examination. Professor
Diener concluded that there are no significant differences
between the patients groups regarding the cognitive and the
functional outcomes.
ESC 13th May 2008
2cond TIA satellite symposium
There was a discussion in the
symposium today 13th May 08 regarding the term TIA
and whether it should be called unstable TIA, acute cerebral
ischaemia or acute cerebral vascular syndrome. It was clear in
the conference today that there was no consensus on the term
TIA. At the end of the session Dr. Peter Sandercook/UK wanted
the audience to have a vote by raising hands to chose which term
they think it is more suitable to replace the TIA one.
In the next session regarding TIA
and its differential diagnosis Prof. Henerrici, Germany
mentioned that TIA and stroke should have the same emergency
workout. He referred to a study in his centre which is going to
be presented as a poster later today in which his team has
studied 120 patients with TIA. It was found that the risk of
stroke is 11.7%. Prof Hennerici mentioned in his lecture that
ABCD2 score and DW1 are useful in combination for TIA risk
stratification.
The next speaker was Prof.
Dienner from Germany who was talking about how to define outcome
parameters of TIA in Randomised Controlled Trials (RCT). He
concluded that TIA should not be an endpoint in RCT as it is
very difficult to diagnose. There was another presentation
regarding the MRI and its vascular contributions from Dr.
Schwartz in Hannover. He pointed out that DW1 can show a
positive proof of ischaemia or cytotoxic injury. However, there
are few other differential diagnoses that MRI can help in
exploring such as migraine, venous congestion, focal epilepsy
and cortical arterial hypertension in pregnancy. It will help in
making the diagnosis clear for arteriovenous malformation cases
as well.
DWI MRI can help in planning the
therapeutic intervention according the message from Dr. Schwartz
in this TIA satellite symposium as part of the 17th
European stroke conference in Nice, France.
ABCD2 score
and TIA
The Study concluded that the ABCD2
score may be an useful tool not only to predict recurrence of minor
stroke or TIA but also in screening for diagnosis. Patients with
ABCD2 score of 3 and above might be targeted for rapid assessment
and treatment if there are limited clinic resources. These results
require validation in larger patient groups.
Antihypertensive therapy in
thrombolysed stroke patients: Results from SITS-ISTR
The results of this study suggest a
more active blood pressure lowering approach in moderate
hypertension is indicated early after intravenous thrombolysis. In
particular, not providing antihypertensive therapy in known
hypertensives was associated with worse outcome and initiation of
new antihypertensive therapy in moderate hypertension seemed to have
a favourable outcome.
Is it time to reassess the
SITS-MOST criteria for thrombolysis?
This study concluded that more than
one-third of patients not fulfilling SITS-MOST criteria benefit from
tPA treatment. The authors continued to say that extension of
SITS-MOST criteria should be considered in future studies
Thrombolysis in young patients: the SITS-MOST data.
The data of this study confirm that outcomes are better in young
ischaemic stroke patients compared to older ones after treatment
with intravenous t-PA. However, a more detailed critical analysis of
indicators that might predict outcome and/or different response to
intravenous thrombolysis between the two age subgroups is warranted.
Ischemic Stroke Outcome at
90 Days
The authors mentioned that their
data show a negative correlation between early plasma levels of
inflammatory biomarkers - in particular TIMP-1, IL-6, CRP, and S-100
- and stroke outcome at 90 days. Patients with full recovery in
functional scores show a different time course of biomarkers
compared to those with poor clinical outcome. Interestingly 90d
after stroke significant differences in levels of TIMP-1, MCP-1,
IL-6, and CRP depending on stroke severity are still detected.
Risk factors for cerebral
infarction
In a specialized session for the
risk factors of stroke, this paper from Sweden concluded that
conventional cardiovascular risk factors remain major determinants
of stroke. The relative importance of individual risk factors is
changing over time with increasing contribution of atrial
fibrillation and hypertension and decreasing contribution of smoking
in men. The prospects for better primary prevention of stroke are
evident. This study was done on 66 610 patients reported to the
Swedish National Quality Register for Stroke Care (Riks-Stroke).
Metabolic syndrome (MetS) in
lacunar stroke (LS|)
This study concluded that the
prevalence of MetS in ischaemic stroke patients is high. LS patients
without white matter lesions (WML) significantly more often had MetS
than LS patients with WML. As no difference was found between the LS
patients without WML and cortical stroke (CS) patients, MetS is
possibly more strongly related to atherosclerotic disease (e.g. LS
without WML) than with small vessel disease (LS with WML). The
results therefore suggest a different, non-atherosclerotic
pathophysiology underlying LS with WML.
Effectiveness of statin
treatment in patients with a recent TIA or ischemic stroke
The benefit of statins in patients
with acute ischaemic stroke or TIA has been demonstrated in
Randomised controlled trial. Effectiveness in daily practice may
however be violated by a different patient population and less
patient compliance.
This study concluded thattThe effect
of statins on the occurrence of vascular events within 3 years in
this study is similar to the effect observed in RCT's.
Prevention regimen for
effectively preventing second strokes (PRoFESS) Trial
There is a high risk of recurrent
stroke following an initial stroke or transient ischaemic attack. A
combination of acetylsalicylic acid (ASA) and extended release
dipyridamole (ER-DP) or clopidogrel were superior to ASA in
secondary stroke prevention trials. The Prevention Regimen for
Effectively Avoiding Secondary Strokes (PRoFESS) trial, the largest
secondary stroke prevention trial to date, investigated whether the
fixed-dose combination of ASA plus ER-DP compared to clopidogrel
reduced the risk of recurrent strokes. There will be another study
in the conference regarding Profess trial. The results of which will
elucidate the role of telmisartan in addition to usual care in the
prevention of recurrent stroke.
Endarterectomy versus
Angioplasty in patients with Symptomatic Severe carotid Stenosis
This trial was stopped prematurely
after the inclusion of 527 patients for reasons of both safety and
futility. The 30-day risk of any stroke or death was significantly
higher after stenting (9.6%) than after endarterectomy (3.9%),
resulting in a relative risk of 2.5 (95% CI, 1.2 to 5.1). Long-term
outcomes after a mean follow-up of more than 3 years will be
presented.
Examination of depression in
those with mild stroke
This study concluded that despite
minimal functional disability, community dwelling subcortical stroke
survivors report depression that is sustained over time and is at a
higher proportion than those in the community without stroke.
Recognition of risk factors for depression over time in this
sub-group is critical for optimizing post-stroke care.
Blood biomarkers to improve
prediction of the prognosis in ischaemic stroke
This systematic review concluded
that no class of marker, other than those of cardiac damage, was
reasonably consistently associated with poor outcome. Methods were
weak: none assessed if the biomarker added predictive ability to a
clinical model, few were blinded & cohorts were no ideal. The
authors suggested that future studies should: prespecify outcomes,
blind measurement of biomarker and outcome, examine unselected
cohorts of stroke patients & assess if biomarkers add power to
validated clinical models.
Effect of intravenous
thrombolysis in acute ischaemic stroke on outcome in daily
practice
Thrombolysis with intravenous
thrombolysis has been proven effective for treatment of patients
with acute ischaemic stroke randomised clinical trials. In daily
practice, the effect of thrombolysis may be less because of
co-morbidity, less strict contra-indications and treatment by less
experienced doctors.
This study ,however, confirms that
intravenous thrombolysis for acute ischaemic stroke improves outcome
also in standard practice, outside the setting of a randomised
clinical trial.
Mobile versus Hospital Based
Telestroke Service. A Controlled Analysis
Telemedicine is increasingly used to
provide acute stroke expertise for hospitals without full-time
neurological services.
This study from Germany concluded
that Teleconsultation using a laptop workstation and broadband
mobile telecommunication is technically stable and allows remote
clinical decision making. There remain disadvantages regarding
videoconference quality on the hub side and lack of
video-transmission to the spoke side.
In their original research paper ( Stroke.
2008;39:1205) Smith W S et al mentioned that endovascular mechanical
thrombectomy may be used during acute ischaemic stroke due to large
vessel intracranial occlusion. First-generation MERCI devices
achieved recanalization rates of 48% and, when coupled with
intraarterial thrombolytic drugs, recanalization rates of 60% have
been reported. Enhancements in embolectomy device design may improve
recanalization rates.
Multi MERCI was an international, multicenter, prospective,
single-arm trial of thrombectomy in patients with large vessel
stroke treated within 8 hours of symptom onset. Patients with
persistent large vessel occlusion after IV tissue plasminogen
activator treatment were included. Once the newer generation (L5
Retriever) device became available, investigators were instructed to
use the L5 Retriever to open vessels and could subsequently use
older generation devices and/or intraarterial tissue plasminogen
activator. Primary outcome was recanalization of the target vessel.
The results of the study revealed that one hundred sixty-four
patients received thrombectomy and 131 were initially treated with
the L5 Retriever. Mean age±SD was 68±16 years, and baseline median
National Institutes of Health Stroke Scale score was 19 (15 to 23).
Treatment with the L5 Retriever resulted in successful
recanalization in 75 of 131 (57.3%) treatable vessels and in 91 of
131 (69.5%) after adjunctive therapy (intraarterial tissue
plasminogen activator, mechanical). Overall, favorable clinical
outcomes (modified Rankin Scale 0 to 2) occurred in 36% and
mortality was 34%; both outcomes were significantly related to
vascular recanalization. Symptomatic intracerebral haemorrhage
occurred in 16 patients (9.8%); 4 (2.4%) of these were parenchymal
haematoma type II. Clinically significant procedural complications
occurred in 9 (5.5%) patients.
The study concluded that higher rates of recanalization were
associated with a newer generation thrombectomy device compared with
first-generation devices, but these differences did not achieve
statistical significance. Mortality trended lower and the proportion
of good clinical outcomes trended higher, consistent with better
recanalization.
One of the main complications following
immobility after stroke is the occurrence of venous thromboembolism
(VTE).
The optimal form of pharmacologic prophylaxis following stroke is
unknown.
The researchers identified randomized trials comparing
unfractionated heparin (UFH) to low-molecular-weight heparin (LMWH)
for VTE prevention in ischaemic stroke patients. They focused on the
risk for VTE, pulmonary embolism (PE), bleeding, and mortality as a
function of the type of agent used for prophylaxis (Chest. 2008
Jan;133(1):149-55).
This study showed that the use of LMWH was associated with a
significant risk reduction for any VTE. Limiting the analysis to
proximal VTEs also indicated that LMWHs were superior. LMWH use led
to fewer PEs as well. There were no differences in rates of overall
bleeding, intracranial haemorrhage, or mortality based on the type
of agent employed.
The study concluded that the prophylactic use of LMWH compared to
UFH following ischaemic stroke is associated with a reduction in
both VTE and PE. This benefit is not associated with an increased
incidence of bleeding.
The main message from reading this paper is a broader use of LMWH
for VTE prevention after ischaemic stroke is warranted.
A few international studies suggest an inverse
association of the intake of fat with risk of ischaemic stroke. On
the contrary of coronary heart disease, only 10% a 15% of ischaemic
strokes are associated to large vessels atherosclerosis. This
suggests different mechanisms for these two pathologies. This
study’s aim is to quantify the ischaemic stroke risk associated to
dietary fat (Acta Med Port. 2007 Jul-Aug;20(4):307-18).
It included two hundred ninety seven individuals of both sexes,
hospitalized in the S. João Hospital in Oporto, Portugal, with a
first episode of ischaemic stroke. Six hundred and seventy one
controls of both sexes were also evaluated, selected by random digit
dialing. The target population was Caucasian adults aged 44 years or
older, living in the area served by the above named hospital,
without cognitive abnormalities and who had not changed their
dietary habits in the past year.
The information was obtained by a structured questionnaire, by
interview that included socio-demographic, medical and behavioural
aspects (physical activity, tobacco use, food habits). Food intake
in the past year was evaluated by a validated, semi-quantitative
food frequency questionnaire.
The results of the study showd that lipids accounted for less than
30% of the total energy and less than 10% were saturated fatty acids
and polyunsaturated fatty acids but the cholesterol ingestion in men
were higher than 300 mg. The increasing quartiles of total lipids,
monounsaturated, polyunsaturated and saturated fatty acids and
cholesterol were independent protective risk factors.
However, the intake of trans fatty acids increases the risk. Intake
of oleic and linolenic fatty acids only had significant protection
in women while intake of all n-3 fatty acids, dodecohexanoic acid in
particular, had a significant protective effect in both sexes.
The study concluded that the total intakes of fat, saturated fat,
monounsaturated fat and polyunsaturated fat were associated with
reduced risk of ischaemic stroke of both sexes.
TIA or transient ischaemic attack is an acute
loss of focal cerebral function with symptoms last less than 24
hours. Previous studies have suggested that the risk of recurrent
stroke is up to 10% in the week after a transient ischaemic attack
(TIA) or minor stroke. Modelling studies suggest that urgent use of
existing preventive treatments could reduce the risk by 80–90%, but
in the absence of evidence many health-care systems make little
provision. Professor Peter Rothwell et al’s aim was to determine the
effect of more rapid treatment after TIA and minor stroke in
patients who are not admitted direct to hospital (The Lancet 2007;
370:1432-1442).
The research team did a prospective before (phase 1: April 1, 2002,
to Sept 30, 2004) versus after (phase 2: Oct 1, 2004, to March 31,
2007) study of the effect on process of care and outcome of more
urgent assessment and immediate treatment in clinic, rather than
subsequent initiation in primary care, in all patients with TIA or
minor stroke not admitted direct to hospital. The study was nested
within a rigorous population-based incidence study of all TIA and
stroke (Oxford Vascular Study; OXVASC), such that case
ascertainment, investigation, and follow-up were complete and
identical in both periods. The primary outcome was the risk of
stroke within 90 days of first seeking medical attention, with
independent blinded (to study period) audit of all events.
The findings of the study showed that of the 1278 patients in OXVASC
who presented with TIA or stroke (634 in phase 1 and 644 in phase
2), 607 were referred or presented direct to hospital, 620 were
referred for outpatient assessment, and 51 were not referred to
secondary care. 95% (n=591) of all outpatient referrals were to the
study clinic. Baseline characteristics and delays in seeking medical
attention were similar in both periods, but median delay to
assessment in the study clinic fell from 3 (IQR 2–5) days in phase 1
to less than 1 (0–3) day in phase 2 (p<0•0001), and median delay to
first prescription of treatment fell from 20 (8–53) days to 1 (0–3)
day (p<0•0001). The 90-day risk of recurrent stroke in the patients
referred to the study clinic was 10•3% (32/310 patients) in phase 1
and 2•1% (6/281 patients) in phase 2; there was no significant
change in risk in patients treated elsewhere. The reduction in risk
was independent of age and sex, and early treatment did not increase
the risk of intracerebral haemorrhage or other bleeding.
The authors concluded that early initiation of existing treatments
after TIA or minor stroke was associated with an 80% reduction in
the risk of early recurrent stroke.
Patients with transient ischaemic attack (TIA) or
minor stroke are at high immediate risk of stroke. The optimum early
treatment options for these patients are not known.
Within 24 h of symptom onset, the authors of this study randomly
assigned, in a factorial design, 392 patients with TIA or minor
stroke to clopidogrel (300 mg loading dose then 75 mg daily; 198
patients) or placebo (194 patients), and simvastatin (40 mg daily;
199 patients) or placebo (193 patients). All patients were also
given aspirin and were followed for 90 days (Lancet Neurology 2007;
6:961-969)
Descriptive analyses were done by intention to treat. The primary
outcome was total stroke (ischaemic and haemorrhagic) within 90
days. Safety outcomes included haemorrhage related to clopidogrel
and myositis related to simvastatin.
The median time to stroke outcome was 1 day (range 0–62 days). The
trial was stopped early due to a failure to recruit patients at the
prespecified minimum enrolment rate because of increased use of
statins. 14 (7•1%) patients on clopidogrel had a stroke within 90
days compared with 21 (10•8%) patients on placebo. 21 (10•6%)
patients on simvastatin had a stroke within 90 days compared with 14
(7•3%) patients on placebo.
The interaction between clopidogrel and simvastatin was not
significant (p=0•64). Two patients on clopidogrel had intracranial
haemorrhage compared with none on placebo. There was no difference
between groups for the simvastatin safety outcomes.
Immediately after TIA or minor stroke, patients are at high risk of
stroke, which might be reduced by using clopidogrel in addition to
aspirin. The haemorrhagic risks of the combination of aspirin and
clopidogrel do not seem to offset this potential benefit. The
authors were unable to provide evidence of benefit of simvastatin in
this setting. This aggressive prevention approach merits further
study.
The Lancet Neurology (Lancet Neurology 2007;
6:830-838) has published in it’s latest issue a personal view about
the subject of using homocystine- lowering agents in stroke
prevention.
On the basis of the results of several recent clinical trials, many
researchers have concluded that vitamin therapy designed to lower
total homocysteine concentrations is not effective in reducing the
risk of cardiovascular events. However, whereas almost all
myocardial infarctions are due to plaque rupture, stroke has many
more pathophysiological mechanisms, and thrombosis—which is
increased by raised total homocysteine concentrations—has an
important role in many of these processes. Thus, stroke and
myocardial infarction could respond differently to vitamin therapy.
A detailed assessment of the results of the recent HOPE-2 trial and
a reanalysis of the VISP trial restricted to patients capable of
responding to vitamin therapy suggest that higher doses of vitamin
B12 and perhaps new approaches to lowering total homocysteine
besides routine vitamin therapy with folate, vitamin B6, and vitamin
B12 could reduce the risk of stroke. The author concluded that
lowering homocysteine level could still help to prevent stroke, if
not other vascular outcomes.
Anticoagulants are more effective than
antiplatelet agents at reducing stroke risk in patients with atrial
fibrillation, but whether this benefit outweighs the increased risk
of bleeding in elderly patients is unknown. Mant J et al assessed
whether warfarin reduced risk of major stroke, arterial embolism, or
other intracranial haemorrhage compared with aspirin in elderly
patients (The Lancet 2007; 370:493-503).
The trial (the Birmingham Atrial Fibrillation Treatment of the Aged
Study, BAFTA) recruited 973 patients aged 75 years or over (mean age
81•5 years, SD 4•2) with atrial fibrillation from primary care and
randomly assigned to warfarin (target international normalised ratio
2–3) or aspirin (75 mg per day). Follow-up was for a mean of 2•7
years. The primary endpoint was fatal or disabling stroke (ischaemic
or haemorrhagic), intracranial haemorrhage, or clinically
significant arterial embolism. Analysis was by intention to treat.
There were 24 primary events (21 strokes, two other intracranial
haemorrhages, and one systemic embolus) in people assigned to
warfarin and 48 primary events (44 strokes, one other intracranial
haemorrhage, and three systemic emboli) in people assigned to
aspirin. Yearly risk of extracranial haemorrhage was 1•4% (warfarin)
versus 1•6% (aspirin).
These data support the use of anticoagulation therapy for people
aged over 75 who have atrial fibrillation, unless there are
contraindications or the patient decides that the benefits are not
worth the inconvenience. This trial will have huge implications on
the practice of stroke medicine and on the implementation of the
effective strategy to prevent cardiovascular diseases in the elderly
with atrial fibrillation.
There are limited and
conflictingdata on gender differences in clinical
outcomes among patientswith symptomatic intracranial
arterial stenosis. This study (Stroke
2007; 38:2055) examined gender differences in patients enrolled in
the Warfarin-AspirinSymptomatic Intracranial Disease (WASID)
Study.
Participants were 569 men and
women with symptomaticintracranial arterial stenosis.
They were followed-up for theoccurrence of ischaemic
stroke and the combined end point ofstroke or vascular
death from February 1999 through July 2003(mean
follow-up, 1.8 years).
Two-year rates of the primary
end point were28.4% and 16.6% for women and men,
respectively. The probabilities of ischaemic stroke (P=0.005)and of the combined end point of stroke or vascular death (P=0.017)over time were significantly higher in women than men. Womenhad a greater multivariate-adjusted risk for ischaemic stroke
and for the combinedend point of stroke or vascular
death.
The study concluded that women
with symptomatic intracranial arterialstenosis are at
significantly greater risk for ischaemic strokeand for
the combined end point of stroke or vascular death.These
findings suggest the need for vigorous screening of risk
factors and for aggressive management of risk factors and strokein women. They also suggest the need to ensure adequate
numbersof women in clinical trials designed to explore
new and promisingtherapies for intracranial arterial
stenosis.
Pain and
spastic shoulder are frequent in hemiplegia following a stroke.
Shoulder pain is a major problem for these patients, interfering
with physiotherapy, sleep and daily activities.
This randomised, double blind, placebo controlled, two parallel
group study was conducted to assess the beneficial effect of
injection of botulinum toxin A (Dysport) into the subscapularis
muscle on shoulder pain in stroke patients with spastic hemiplegia
(Journal of Neurology, Neurosurgery, and Psychiatry
2007;78:845-848).
A single dose of botulinum toxin A (500 Speywood units) or placebo
was injected into the subcapularis muscle. Pain was assessed using a
10 point verbal scale. Subscapularis spasticity was assessed by the
change in passive shoulder lateral rotation and abduction. Upper
limb spasticity was assessed using the Modified Ashworth Scale for
shoulder medial rotators, and elbow, wrist and finger flexors.
Assessments were carried out at baseline and at weeks 1, 2 and 4.
Twenty patients (10 patients per group), 11 with ischaemic stroke
and 9 with haemorrhagic stroke, completed the study. Pain
improvement with botulinum toxin A was observed from week 1; score
difference from baseline at week 4 was 4 points versus 1 point with
placebo (p = 0.025). Lateral rotation was also improved, with a
statistically significant difference compared with placebo at week 2
(p = 0.05) and week 4 (p = 0.018). A general improvement in upper
limb spasticity was observed; it was significant for finger flexors
at week 4 (p = 0.025).
The study concluded that subscapularis injection of botulinum toxin
A appears to be of value in the management of shoulder pain in
spastic hemiplegic patients. The results confirm the role of
spasticity in post-stroke shoulder pain.
Cilostazol is an antiplatelet agent that inhibits phosphodiesterase
III in platelets and vascular endothelium. Many RCTs have
demonstrated the efficacy and safety of cilostazol, but the data
were limited. A research team from Tokyo Women’s Medical University
in Japan conducted a meta-analysis of these RCTs to verify the
effects of cilostazol on ischaemic and haemorrhagic events.
Data
from 13 randomized placebo-controlled trials involving 6165 patients
were analysed. Endpoints examined for safety and efficacy were
cerebrovascular events, cardiovascular events and bleeding
complications. Relative risk and 95% confidence interval were
estimated using the Mantel-Haeszel model.
The
results showed that the 13 trials included 10 trials in patients
with peripheral artery disease, 2 in those with cerebrovascular
disease and 1 in those with coronary stenting. Of 6165 patients,
4383 (71%) patients were males, and mean age was 64.9 years. There
was no difference in patient backgrounds between the groups.
Incidence of total vascular events was significantly lower in the
cilostazol group.
A
significantly lower incidence of cerebrovascular events was seen in
the cilostazol group compared to the placebo group but there was no
significant difference in the incidence of cardiovascular events
between the groups. There was no difference in the incidence of
serious bleeding complications between the cilostazol (1.4%) and
placebo (1.5%) groups.
This
first meta-analysis of Cilostazol conducted on over 6000 patients
with a history of vascular events demonstrated a great preventive
effect of cilostazol on cerebrovascular events with no associated
increase in cardiovascular or bleeding risks.
The results of
the 2006 National Sentinel Audit for Stroke in UK show that patients
in Wales are more likely to die from stroke, or if they survive will
have higher levels of disability than in England or Northern
Ireland.
The Audit,
funded by the Healthcare Commission, was carried out on behalf of
the Intercollegiate Stroke Group by the Royal College of Physicians,
London’ Clinical Effectiveness and Evaluation Unit (CEEu), and
covers 100% of eligible hospitals in England and Wales. As in 2005,
results for each participating site are published on the RCP
website:
http://www.rcplondon.ac.uk/pubs/books/strokeaudit/strokeaudit2006.pdf
The late launch
of a National Service Framework in Wales in 2006 appears to have
handicapped the development of specialist stroke services in Wales,
which need urgent attention. Only 45% of eligible hospitals in Wales
(nine hospitals) have a stroke unit, compared with 97% of eligible
hospitals in England. Only 3 sites (15%) have acute stroke unit
provision. Given the evidence for the benefits of stroke units, the
very low rate of stroke unit provision and admission is
unacceptable.
Only 28% of patients in
Wales were treated in a stroke unit during their stay compared
to 64% in England and 73% in Northern Ireland
Only 22% of patients in
Wales spent more than half their time on a stroke unit (56%
England, 60% NI)
Patients managed on stroke
units have much better results than patients looked after in
other settings – they are much more likely to have had their
ability to swallow checked, to have started aspirin within 48
hours, been assessed by therapists within the recommended times;
had rehabilitation goals documented and have a home visit
performed before discharge
Only 38% of patients had
brain imaging to confirm their diagnosis within 24 hours of the
onset of symptoms, a figure similar to England (43%) and NI
(40%). This figure is unacceptably low and must be improved.
Patients need a brain scan to determine if it is appropriate to
prescribe aspirin – if given within 48 hours of the stroke this
can save lives and reduce disability
The percentage of patients
screened for swallowing disorders in Wales was 55% compared to
67% in England and 62% in Northern Ireland
Physiotherapy assessment
within the first 72 hours of admission was carried out in 54% of
patients in Wales, compared to 72% in England and 74% in
Northern Ireland
The audit
concludes that Wales needs to identify systems to raise the quality
of stroke across the whole patient pathway, particularly through the
development of stroke units.
Dr Tony Rudd,
Chair of the Intercollegiate Stroke Network and Associate Director
of the RCP Clinical Effectiveness and Evaluation Unit, said:
"While there
have been some welcome improvements in the quality of stroke care
over the last two years there are still too many patients who
receive substandard care which is likely to result in higher death
rates or greater disability than necessary. The failure of the
majority of hospitals in Wales to offer stroke unit care is
scandalous and needs urgent action"
Further results from
the audit showed that:
62% of patients were admitted to a stroke unit at
some point in their stay, compared to 46% in 2004. 54% spent over
half their stay in a stroke unit (40% in 2004). This is a
significant and welcome improvement, as now 91% of hospitals have a
stroke unit (79% in 2004) but there is still a lack of capacity
The most dramatic rise in
stroke units was in England, which improved from 82% in 2004 to
97% in 2006, while in Wales the number of stroke units is 9
(45%), the same as in 2004
76% of patients with minor
stroke in hospital for less than 2 days are not being managed on
specialist units. These patients have a high risk of having
another stroke and should receive expert care and investigation
Mean length of stay has
fallen considerably over the last two cycles of audit from 27.9
days in 2004 and 34 days in 2001, to 25.4 days in 2006. These
shorter lengths of stay are not due to patients being moved too
early into care homes, as the audit measures transfer to care
homes separately and there is no change from the 2004 figure of
13%.
The proportion of patients
with mild stroke has fallen from 29% in the 2004 audit to 24% in
2006, suggesting that such patients are being discharged earlier
without the opportunity to complete their rehabilitation – this
is worrying as there has been no significant increase in
specialist community rehabilitation teams
Early access to a stroke
unit has improved since 2004, but only 15% of patients are
admitted to a stroke unit on the same day and only 12% of
patients are being admitted directly to a stroke unit (within 4
hours of arrival at hospital)
Only 42% of patients had
brain imaging to confirm their diagnosis within 24 hours of the
onset of symptoms. This figure is unacceptably low and must be
improved. Patients need a brain scan to determine if it is
appropriate to prescribe aspirin – if given within 48 hours of
the stroke this can save lives and reduce disability
Only 9% of patients were
scanned within 3 hours of stroke – if not scanned on the day of
admission, they normally have to wait until the next working day
- this is a particular problem if admitted at the weekend as
very few scans are performed outside the hours of 8.00 am-6.00
pm
Problems remain with
stroke patients getting access to therapists and social workers
– a third of patients who have difficulty swallowing have not
been assessed by a Speech and Language Therapist within 72 hours
of admission or within 7 days for those having difficulty
communicating. The situation is similar for physiotherapy and
for occupational therapy and social work it is even worse
The objective of this study was to estimate the
high blood pressure values and the 10-year risk of stroke in the
Spanish general population aged 60 years or older using the
Framingham scale (Stroke. 2007; 38:1167.)
This study was a multicenter, population-based, cross-sectional one
performed in Spanish primary care centers. A randomized selection of
centers and recruitment population was used.
The research team analyzed 7343 subjects (mean age, 71.6 years;
standard deviation, 7.0; 53.4% females, 34.4% obese subjects, and
27.1% diabetic subjects). Electrocardiographic–left ventricle
hypertrophy was present in 12.9% of the subjects, atrial
fibrillation in 8.4%, and established cardiovascular disease in
28.9%; 73.0% already had hypertension diagnosed, and 12.8% showed
high blood pressure without a prior diagnosis of hypertension. Among
hypertensive subjects, 29.1% had high blood pressure on therapeutic
objective, and of the total population 35.7% had high blood pressure
under control. Those with hypertension already diagnosed showed a
higher prevalence of other stroke risk factors (left ventricle
hypertrophy, atrial fibrillation, diabetes, or established
cardiovascular disease). The estimated 10-year stroke risk was
19.6%, and was greater in hypertensive patients than in patients
with high blood pressure without known hypertension, or in
normotensive subjects.
The study concluded that the 10-year estimated stroke risk was
19.6%, and it was greater in hypertensive patients as compared with
the remainder people at any blood pressure range. The concomitant
stroke risk factors are more prevalent in patients with hypertension
already diagnosed, which implies an important additional estimated
risk of stroke.
The objective of this study (J Neurol. 2007 Mar
14) is to determine independent clinical predictors of
stroke-associated pneumonia (SAP) that are available in all patients
on day of hospital admission.
The authors studied 236 patients with acute ischaemic stroke
admitted to the neurological intensive care unit at our university
hospital. Risk factors of SAP and of non-responsivity of early-onset
pneumonia (EOP; onset within 72 hours after admission) to initial
antibacterial treatment were analyzed.
The results showed that the incidence of SAP was 22%. The following
independent risk factors were found to predict SAP with 76% (EOP:
90%) sensitivity and 88% specificity: dysphagia, National Institute
of Health Stroke Scale >/= 10, non-lacunar basal-ganglia infarction,
and any other infection present on admission. Excluding the patients
with other infections on admission, the same independent risk
factors (except infection) were found. Further, but not independent
risk factors were: combined brainstem and cerebellar infarction,
infarction affecting more than 66% of middle cerebral artery
territory, hemispheric infarction exceeding middle cerebral artery
territory, impaired vigilance, mechanical ventilation, age >/= 73
years, current malignoma, and cardioembolic stroke, whereas patients
with lacunar infarctions had significantly lower risk. In contrast
to previous reports, no impact of male gender or diabetes was found.
Initial vomiting, especially if associated with impaired vigilance,
predicted antibacterial treatment non-responsivity of EOP. In
non-responders exclusively fungal pathogens were identified.
The study concluded that increased risk of pneumonia in acute stroke
patients can be sufficiently predicted by a small set of clinical
risk factors
Venous thromboembolism prophylaxis with low molecular weight heparin
or unfractionated heparin is recommended in acute ischaemic stroke,
but which regimen provides optimum treatment is uncertain. The
clinicians in this study aimed to compare the efficacy and safety of
enoxaparin with that of unfractionated heparin for patients with
stroke (The Lancet 2007; 369:1347-1355)
The researchers has randomly assigned 1762 patients with acute
ischaemic stroke who were unable to walk unassisted within 48 h of
symptoms to receive either enoxaparin 40 mg subcutaneously once
daily or unfractionated heparin 5000 U subcutaneously every 12 h for
10 days (range 6–14). Patients were stratified by National
Institutes of Health Stroke Scale (NIHSS) score (severe stroke ≥14,
less severe stroke <14). The primary efficacy endpoint was the
composite of symptomatic or asymptomatic deep vein thrombosis,
symptomatic pulmonary embolism, or fatal pulmonary embolism. Primary
safety endpoints were symptomatic intracranial haemorrhage, major
extracranial haemorrhage, and all-cause mortality.
In the efficacy population (ie, one or more dose received, presence
of deep vein thrombosis or pulmonary embolism, or assessment for
venous thromboembolism), enoxaparin (n=666) and unfractionated
heparin (669) were given for 10•5 days.
Enoxaparin reduced the risk of venous thromboembolism by 43%
compared with unfractionated heparin; this reduction was consistent
for patients with an NIHSS score of 14 or more or less than 14. The
occurrence of any bleeding was similar with enoxaparin or
unfractionated heparin.
The frequency of the composite of symptomatic intracranial and major
extracranial haemorrhage was small and closely similar between
groups. The clinicians noted no difference for symptomatic
intracranial haemorrhage between the groups; the rate of major
extracranial bleeding was higher with enoxaparin than with
unfractionated heparin.
The results suggest that for patients with acute ischaemic stroke,
enoxaparin is preferable to unfractionated heparin for venous
thromboembolism prophylaxis in view of its better clinical benefits
to risk ratio and convenience of once daily administration.
Hyperglycaemia after acute stroke is a common finding that has been
associated with an increased risk of death. The researchers sought
to determine whether treatment with glucose-potassium-insulin (GKI)
infusions to maintain euglycaemia immediately after the acute event
reduces death at 90 days (Lancet Neurology 2007; 6:397-406).
Patients presenting within 24 h of stroke onset and with admission
plasma glucose concentration between 6•0–17•0 mol/L were randomly
assigned to receive variable-dose-insulin GKI (intervention) or
saline (control) as a continuous intravenous infusion for 24 h. The
purpose of GKI infusion was to maintain capillary glucose at 4–7
mmol/L, with no glucose intervention in the control group.
The primary outcome was death at 90 days, and the secondary endpoint
was avoidance of death or severe disability at 90 days. Additional
planned analyses were done to determine any differences in residual
disability or neurological and functional recovery. The trial was
powered to detect a mortality difference of 6% (sample size 2355),
with 83% power, at the 5% two-sided significance level. This study
is registered as an International Standard Randomised Controlled
Trial (number ISRCTN 31118803)
The trial was stopped due to slow enrolment after 933 patients were
recruited. For the intention-to-treat data, there was no significant
reduction in mortality at 90 days.
There were no significant differences for secondary outcomes. In the
GKI group, overall mean plasma glucose and mean systolic blood
pressure were significantly lower than in the control group.
The study concluded that GKI infusions significantly reduced plasma
glucose concentrations and blood pressure. Treatment within the
trial protocol was not associated with significant clinical benefit,
although the study was underpowered and alternative results cannot
be excluded.
Despite evidence of
a genetic role in stroke, the identification of common genetic risk
factors for this devastating disorder remains problematic. The
researchers aimed to identify any common genetic variability
exerting a moderate to large effect on risk of ischaemic stroke, and
to generate publicly available genome-wide genotype data to
facilitate others doing the same (Lancet Neurology 2007; 6:414-420)
The researchers applied a genome-wide high-density
single-nucleotide-polymorphism (SNP) genotyping approach to a cohort
of samples with and without ischaemic stroke (n=278 and 275,
respectively), and did an association analysis adjusted for known
confounders in a final cohort of 249 cases and 268 controls. More
than 400 000 unique SNPs were assayed.
The authors produced more than 200 million genotypes in 553 unique
participants. The raw genotypes of all the controls have been posted
publicly in a previous study of Parkinson's disease. From this
effort, results of genotype and allele association tests have been
publicly posted for 88% of stroke patients who provided proper
consent for public release. Preliminary analysis of these data did
not reveal any single locus conferring a large effect on risk for
ischaemic stroke.
The data generated here comprise the first phase of a genome-wide
association analysis in patients with stroke. Release of phase I
results generated in these publicly available samples from each
consenting individual makes this dataset a valuable resource for
data-mining and augmentation.
Malignant infarction
of the middle cerebral artery (MCA) is associated with an 80%
mortality rate. Non-randomised studies have suggested that
decompressive surgery reduces this mortality without increasing the
number of severely disabled survivors. To obtain sufficient data as
soon as possible to reliably estimate the effects of decompressive
surgery, results from three European randomised controlled trials
(DECIMAL, DESTINY, HAMLET) were pooled. The trials were ongoing when
the pooled analysis was planned (Lancet Neurology 2007; 6:215-222).
Individual data for patients aged between 18 years and 60 years,
with space-occupying MCA infarction, included in one of the three
trials, and treated within 48 h after stroke onset were pooled for
analysis. The protocol was designed prospectively when the trials
were still recruiting patients and outcomes were defined without
knowledge of the results of the individual trials. The primary
outcome measure was the score on the modified Rankin scale (mRS) at
1 year dichotomised between favourable (0–4) and unfavourable (5 and
death) outcome. Secondary outcome measures included case fatality
rate at 1 year and a dichotomisation of the mRS between 0–3 and 4 to
death. Data analysis was done by an independent data monitoring
committee.
The study concluded that in patients with malignant MCA infarction,
decompressive surgery undertaken within 48 h of stroke onset reduces
mortality and increases the number of patients with a favorable
functional outcome. The decision to perform decompressive surgery
should, however, be made on an individual basis in every patient.
The preventive effect of anticoagulation in
patients with stroke and atrial fibrillation (AF) is documented only
in trials of minor stroke. Although anticoagulation reduced stroke
recurrence, those trials did not demonstrate an influence of
anticoagulation on survival.
A nationwide registry that was started in 2001 with the aim of
registering all hospitalized stroke patients in Denmark now includes
24 791 patients. The authors studied the survival of patients with
ischaemic stroke and AF with respect to anticoagulation treatment
(stroke. 2007; 38:259). All underwent an evaluation for stroke
severity (according to the Scandinavian Stroke Scale), computed
tomography scan, and an evaluation for cardiovascular risk factors.
Follow-up duration was 4 years (mean, 1.2 years).
Of all patients, 22 179 (89.4%) experienced an ischaemic stroke. In
total, 3670 (16.5%) had AF, and 1909 had no contraindication to
anticoagulation treatment. Anticoagulation treatment was initiated
in 1149 of these patients (60.2%) but omitted in 760 (39.8%) despite
no contraindication to such treatment. Of the patients so treated,
18.9% died during follow-up versus 45.2% without treatment. Patients
who received treatment were younger and had less severe strokes.
The data suggest that anticoagulation treatment reduces poststroke
mortality in patients with ischaemic stroke and AF
Neurobiological Technologies, Inc. (NTI)
announced last month the presentation of new analysis of data from
prior clinical trials of ancrod and updates on the clinical
development of their investigational drug, Viprinex(TM) (ancrod),
for the treatment of acute ischaemic stroke at the American Stroke
Associations' International Stroke Conference 2007. Viprinex is a
definbrinogenating agent derived from the venom of the Malayan pit
viper.
It was mentioned in the international stroke conference 2007 that
"The ancrod data support the role of fibrinogen in influencing
stroke outcome and the potential role for ancrod in treating strokes
by lowering fibrinogen levels,".
The drug trials, known as ASP-I and ASP-II, will evaluate whether a
brief infusion of Viprinex begun up to six hours after onset of
stroke symptoms can minimize neurological damage, while maximizing
functional outcomes in stroke patients. The primary endpoint is
death or disability at 90 days. Each of these trials will enroll 650
patients. Patient accrual began in November 2005 and is expected to
continue into 2008. In the ASP studies, patients will receive a
single two to three hour infusion of Viprinex, leading to a
significantly lower overall dose than that used in previous Phase 3
studies, which employed dosing over five to seven days. The aim is
to lower the fibrinogen rapidly, while avoiding prolonged low
fibrinogen levels. It is hoped that this modified dosing schedule
will improve both the potential safety and efficacy of the drug.
More than 5 million US stroke
survivors require comprehensive care for risk factor modification and
secondary prevention. The objective of this study (Arch Neurol. 2007; 64:37-42) is to assess
age-related differences in access to physician care and medications among
stroke survivors (aged 45-64 years vs 65 years). The study was a US population-based survey.
The participants are the stroke survivors (n = 3681) aged 45 years and
older among 159 985 survey respondents. The main outcome measures of the study are general doctor visit, medical
specialist visit, and inability to afford medications within the last 12
months. The results showed that Compared with older stroke survivors, younger
stroke survivors more frequently reported no general doctor visit, no
general doctor or medical specialist visit, and the inability to afford
medications. Younger age was independently associated with no general
doctor visit, no general doctor or medical specialist visit, and the
inability to afford medications after adjusting for sex, race, income,
neurological disability, health status, and comorbidity. With further
adjustment for health insurance, younger age remained independently
associated with the inability to afford medications but not the lack of
physician visits. The authors concluded that stroke survivors younger than 65 years reported
worse access to physician care and medication affordability than older
stroke survivors. Inadequate access among younger stroke survivors may
lead to inadequate risk factor modification and recurrent cardiovascular
events.
Results from the Reduction of Atherothrombosis for Continued Health
(REACH) Registry
Whether a history of
carotid endarterectomy influences patient compliance with medical
treatments and physician attitude toward treatments after ischaemic stroke
or transient ischaemic attack (TIA) is not well known. The researchers studied the baseline data of 18 467 ischaemic stroke and
TIA patients from the international REduction of Atherothrombosis for
Continued Health (REACH) Registry and investigated the impact of a history
of endarterectomy on the secondary medical prevention measured by the use
of antiplatelet agents and statins, and by the control of cholesterol
level, glucose level, and blood pressure ( Stroke. 2006; 37: 2880.). Among the patients with a history of ischaemic stroke or TIA, those with a
history of endarterectomy (n=1474) were more likely to receive
antiplatelet agents and statins, to have a blood pressure <140/90 mm Hg,
and a fasting total cholesterol <200 mg/dL. In diabetic patients,
endarterectomy was associated with lower fasting blood glucose levels. In
multivariate logistic regression analyses, endarterectomy was
significantly associated with the use of antiplatelet agents and statins,
and with a cholesterol level <200 mg/dL. By contrast, the associations
with blood pressure and blood glucose levels were no longer significant.
There was no heterogeneity across the world regions or among the
specialists who enrolled the patients. The study concluded that carotid endarterectomy is associated with a
higher use of antiplatelet agents and statins in stroke/TIA patients. The
absence of such an association with blood pressure and blood glucose
control suggests that the individual determinants of the quality of the
secondary medical prevention vary from one risk factor to another and from
one class of drugs to another.
Elevated von Willebrand factor (vWF)
concentrations are associated with an increased risk of ischaemic heart
disease. Several factors influence vWF antigen levels and activity,
including blood group, genetic variability, acute-phase response, and
proteolysis by A Disintegrin and Metalloprotease with ThromboSpondin motif
(ADAMTS13), a determinant of proteolytic cleavage of vWF. The researchers
assessed how these factors affect the relation between vWF and the
occurrence of stroke to understand the underlying mechanism (Stroke. 2006;
37:2672). In a case-control study of 124 first-ever ischaemic stroke patients and
125 age- and sex-matched controls, the authors studied vWF antigen (vWF:Ag),
vWF ristocetin cofactor activity (vWF:RCo), ADAMTS13 activity, the
–1793C/G polymorphism in the vWF gene, and C-reactive protein. vWF antigen and activity levels were significantly higher in cases than in
controls. The relative risk of ischaemic stroke was highest in individuals
in the upper quartile of vWF:Ag and vWF:RCo compared with individuals in
the lowest quartiles. The study concluded that vWF antigen and activity are associated with the
occurrence of acute ischaemic stroke. This relation is unaffected by the
severity of the acute-phase response or by genetic variation or
degradation.
The objective of this
study is to examine the risk and determinants of dementia following a
clinically overt stroke in a prospectively followed cohort of elderly
subjects (Neurology 2006; 67: 1363-1369).
The authors examined the effect of a clinically detectable stroke on the
risk of dementia using prospective data from 335 subjects in the Baltimore
Longitudinal Study of Aging, all of whom were cognitively and
neurologically normal at entry into the study (mean age at entry 75.1 ±
4.2 years).
The results showed that clinically overt strokes are common in our cohort
(cumulative risk by age 90, 15.4%; 95% CI: 10 to 22%) and confer an
increased risk of dementia compared to subjects without stroke. The
majority of patients who became demented after a stroke had evidence of
mild cognitive impairment preceding the stroke (14 of 19). Moreover, a
clinically symptomatic stroke was a major risk factor for the conversion
of mild cognitive impairment to dementia.When cognitive impairment did not
precede the stroke, there was no increase in the risk of subsequent
dementia. Pathologic data indicate that both vascular and Alzheimer
pathology leads to the prestroke impairment.
The study concluded that dementia after stroke may be determined by
cognitive impairments that exist prior to the stroke.
In the hyperacute stage of the cerebrovascular accident, cerebrovascular
ultrasound can be used to determine the vascular pathology, but the
significance of very early findings on ultrasound is unclear. The present
study (Lancet Neurology 2006; 5:835-840) aimed to assess the prognostic
value of doppler ultrasonography within the first hours after stroke for
functional outcome.
In a prospective multicentre design, patients with clinical signs of
ischaemic anterior-circulation stroke were examined by doppler
ultrasonography of the intracranial and extracranial arteries. Patients
were separated into three groups according to the findings: normal
middle-cerebral artery (MCA); branch occlusions; or a main-stem occlusion.
The primary endpoint was functional outcome at 3 months.
The study identified 361 patients with moderate to severe clinical
deficits (National Institutes of Health Stroke Scale score 5–25). Of
these, 121 (34%) had a normal MCA, 176 (48%) had branch occlusions, 7 (2%)
had severe MCA stenosis, and 57 (16%) had a main-stem occlusion. 50 of the
57 (88%) patients with main-stem occlusion were dead or dependent 3 months
after stroke. An occlusion of the main stem of the MCA within 6 h after
stroke was an independent predictor for poor outcome (p=0•0006). 50% of
patients with ultrasonographic diagnosis of branch occlusions and 63% with
normal MCA had a good outcome. Combination of CT scan without early signs
of infarction and a normal MCA resulted in a predictive value of 71% for a
good functional outcome.
The study concluded that cerebrovascular ultrasonography provides
additional functional prognostic information in the hyperacute stage of
ischaemic stroke. The technique is practical in a well-resourced unit, can
be used to identify patients with high risk for poor functional outcome,
and thus would be an appropriate investigation for future trials.
February 2008
