Stroke as a Hot Topic

Introduction
Stroke is the 3rd highest cause of death in UK and the biggest single cause of major disability.
Can occur at any age – most common>70.
80% ischaemic
>50% physically dependant after 6 months
NSF for elderly contains standards for stroke
Risk of further stroke 10-15% 1st year, 5% per year thereafter.
Risk of death 20% die 1st month. Over 5 years 10%/year

Evidence based treatment and prevention

Stroke Units

These have been shown to improve outcome, patients are less likely to die and more likely to recover fully or partially

Antiplatelet agents

Aspirin
•	Meta analysis in1994 showed high risk patients on aspirin had a decreased risk of stroke
Dipyrimadole
•	1996 ESPS2 showed that in those who suffered a ischaemic stroke or TIA, diprimadole was better than placebo but not as good as aspirin in preventing a stroke, and the combination was better than either alone. But, dipyrimadole had no significant effect on the incidence of MI in these patients. However, there were many flaws and criticisms of this study and the beneficial effect of dipyrimadole is in question, the results of ESPRIT are anticipated.
Clopidogrel
•	CAPRIE showed that it was better than aspirin in preventing vascular death in those with PVD.

Cost of preventing one stroke
o	Aspirin £940
o	Aspirin&Dipyrimadole £8718
o	Clopidigrel £34946

Anticoagulation

European AF Trial showed that in those with AF warfarin was better than aspirin at preventing a stroke, but increased risk of bleeding

Cholesterol

Studies have shown that statins decrease the risk of stroke in those with ischaemic heart disease- 4S,CARE, LIPID

Carotid endarterectomy

In those with 70-99% stenosis the risk of major stroke is 20% in 3 years, this is halved by surgery.

Blood pressure

Increased BP increases the risk of stroke.
Studies have shown that by treating hypertension in survivors of stroke can decrease the further incidence by 29%
PROGRESS trial showed that antihypertensives can decrease the recurrence of strokes, even in normotensive patients. Perindopril plus indapamide were used.
LIFE showed losartan was better than atenolol at reducing the risk of stroke.
HOPE see below
ALLHAT trial showed no difference in primary outcomes (MI) for different antihypertensives, however, lisinolpril was significantly less effective at reducing the secondary end point – stroke.

PAPERS

BJGP Oct 2001
Editorial – The primary care gap
Stroke management in the UK is asymmetrical with the greatest effort expended during the early weeks with negligible input during succeeding months. A survey has shown that 2/3 of those 6 months after a stroke have some residual disability, but less than half were receiving any help.
BMJ 1997 showed patients in a stroke unit are less likely to die and are more likely to recover.  Small RCT have been encouraging as regards community programs.
Community stroke rehabilitation should be further researched and expanded, especially in view of the elderly NSF

BMJ Nov 2001
News - Warfarin-Aspirin Recurrent Stroke Study Group
Aspirin and warfarin are equally effective a preventing recurrence of strokes. The overall rate of death did not differ between the two groups, nor did the incidence of major haemorrhage, however, there were significantly more minor haemorrhages in the warfarin group 

BMJ July 2002
A Multicentre Observational study of presentation and early assessment of acute stroke

Showed median delay for presentation to hospital was 6 hours.
37% arrived within 3 hours
50% arrived within 6 hours
The median delay for those using the emergency services was 2 hours
For those arriving via a GP referral the median delay was 7 hours
65% were assessed within 3 hours
The median delay for assessment by a senior Dr was 1 hour
CT was requested within 3 hours in 22% and 8% had a CT within 3 hours

Conclusion
Delays can be reduced by using the emergency services.
The misconception that delays in presentation prevent early specialist management and possible thrombolysis is not justified.

BMJ March 2002
Use of ramipril in preventing stroke: double blind RCT

9297 patients with vascular disease or diabetes plus an additional risk factor. Those with uncontrolled BP were excluded.
Ramipril decreased BP modestly, and the relative risk of stroke was decreased by 32% and the RR of a fatal stroke was reduced by 61%.
Conclusion was that patients  who are at high risk of stroke should be treated with ramipril irrespective of their initial BP and in addition to other preventative methods. 

BMJ March 2002
Editorial - Preventing Stroke

Discussed the HOPE trial and stated that the findings clearly show that ramipril substantially decreased the risk of stroke and TIAs in 9297 patients with high cardiovascular risk.
Hypertension is still the most important risk factor.
HOPE is not a hypertension study
ACE inhibitors may have additional protective effects
Decreased oxidative stress, decreased prolferative and inflammatory responses producing plaque stabilisation. This is supported by then SECURE study that showed a significant reduction in the progression of athersclerosis for ramipril
Cannot assume a class effect
Need to use 10mg ramipril

BMJ March 2002
Alteplase for stroke: money and optimistic claims buttress the “brain attack” campaign.

American Heart Association rated tPA as class 1 intervention for stroke despite controversy about its safety and efficacy. Most of the experts had ties with the manufacturers of alteplase. Genentech contributed $11 million to AHA. Following public scrutiny AHA recently withdrew statements that alteplase for stroke “saves lives”.
There is still controversy surrounding this – in the same issue of the BMJ Saver etal claim that the evidence is in favour of tPA.
Currently it is recommended that tPA is only given in specialist centres within 3 hours of onset of stroke and as part of RCTs.