CARDIOVASCULAR DISEASES

Health Evidence Bulletins - Wales (logo)
Team Leader: Dr David Fone

Date of completion: 30.9.98

7: Stroke

This bulletin is a supplement to, not a substitute for, professional skills and experience. Users are advised to consult the supporting evidence for a consideration of all the implications of a recommendation.

The Statements The Evidence
7.1 Diagnostic imaging
7.1a. Stroke is characterised by an acute onset of neurological deficit lasting more than 24 hours, resulting from cerebral infarction or haemorrhage. Neurological symptoms from a Transient Ischaemic Attack (TIA) resolve completely within 24 hoursi. CT brain scanning to confirm or exclude cerebral haemorrhage is part of the routine assessment of all patients who present with the acute onset of a focal neurological deficit (preferably within 48 hours and no later than seven days)i-iii.
(Health gain notation – 1 "beneficial")
7.1b. MRI scanning enables a positive diagnosis in the early stages of stroke to be made – of benefit if an effective early intervention in defined categories of stroke becomes available. MRI is currently most effectively used for assessment of stroke if thrombosis of dural sinus, deep vein or cortical vein is suspected, and for the positive diagnosis of thrombotic infarctioni,iii.
(Health gain notation – 2 "likely to be beneficial")
7.1c. Practice guidelines including the use of imaging in transient ischaemic attack and acute stroke are availablei.
(Health gain notation – 1 "beneficial")
i. Scottish Intercollegiate Guidelines Network (SIGN). Management of Patients with Stroke I: Assessment, Investigation, Immediate Management and Secondary Prevention. Edinburgh: Royal College of Physicians, 1997
http://www.show.scot.nhs.uk/sign/pdf/sign13.pdf
[Adobe Acrobat reader required]
(Type V evidence – expert opinion)
ii. Stroke. Towards better management: summary and recommendations of a report by the Royal College of Physicians. Journal of the Royal College of Physicians 1990;24:15-19
(Type V evidence – expert opinion)
iii. Culebras A, Kase C, Masdeu JC et al. Practice guidelines for the use of imaging in transient ischaemic attack and acute stroke: a report of the stroke council, American Heart Association. Stroke 1997;28:1480-97
http://www.americanheart.org/Scientific/statements/1997/
079705.html

(Type V evidence – expert opinion)
7.2 Organisation of care and rehabilitation
7.2a. Full medical assessment should be undertaken and multidisciplinary assessment considered for all acute stroke patients to define the nature of the event, the need for investigation, further management, and the need for rehabilitation: evidence based guidelines are availablei.
(Health gain notation – 1 "beneficial")
i. Scottish Intercollegiate Guidelines Network (SIGN). Management of Patients with Stroke I: Assessment, Investigation, Immediate Management and Secondary Prevention. Edinburgh: Royal College of Physicians, 1997
http://www.show.scot.nhs.uk/sign/pdf/sign13.pdf
[Adobe Acrobat reader required]
(Type V evidence – expert opinion)
7.2b. Stoke patients who receive organised inpatient (stroke unit) care are more likely to be alive, independent, and living at home a year after stroke than those receiving conventional care (odds ratio for death 0.81; 95% CI: 0.68, 0.96; p<0.05 and odds ratio for the combined outcome of death or requiring institutional care 0.75; 95% CI: 0.65, 0.87; p<0.0001)i.
(Health gain notation – 2 "likely to be beneficial")
Caveat: Subjective assessment of what constitutes a stroke unit limits the generalisability of the findings, particularly with respect to the relative effects of the differences in specific management in different models of the "stroke units" identified. Further research and cost-benefit assessments are required.
i. Stroke Unit Trialists’ Collaboration. Organised inpatient (stroke unit) care after stroke. Cochrane Review [updated 17 March 1998]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 18 trials including 3249 patients with median 12 month follow-up)

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7.2c. There is some evidence that formal rehabilitation after stroke is effective in prolonging short term survivali but not long term survival and function (long term survival odds ratio 1.20; 99% CI: 0.84, 1.55)ii. Rehabilitation is best provided by well organised multi-disciplinary teamsi.
There is some evidence to suggest that remedial therapy services (speech, occupational and physiotherapy) should be provided in hospital and in the communityi.
(Health gain notation – 2 "likely to be beneficial")
Caveat: There are few well designed and reliable randomised controlled trials that assess the effectiveness of rehabilitation after stroke. Further good quality research is required.
i. Freemantal N, Pollock C, Sheldon TA, et al. Stroke Rehabilitation. Effective Health Care Number 2. Leeds: School of Public Health, University of Leeds, 1992
http://www.york.ac.uk/inst/crd/ehcb.htm
(Type II evidence – narrative summary review of randomised and non-randomised trials)
ii. Evans RL, Connis RT, Hendricks RD et al. Multisciplinary rehabilitation versus medical care: a meta-analysis. Social Science and Medicine 1995;40(12):1699-1706
(Type I evidence – systematic review and meta-analysis of 2183 patients in 11 studies)
7.2d. Evidence-based clinical guidelines for management of dysphagiai and post-stroke rehabilitation are availableii,iii.
(Health gain notation – 1 "beneficial")
i. Scottish Intercollegiate Guidelines Network (SIGN). Management of Patients with Stroke III: Identification and Management of Dysphagia. Edinburgh: Royal College of Physicians, 1997
http://www.show.scot.nhs.uk/sign/html/html20.htm
(Type V evidence – expert opinion)
ii. Scottish Intercollegiate Guidelines Network (SIGN). Management of Patients with Stroke IV: Rehabilitation, Prevention and Management of Complications, and Discharge Planning. Edinburgh: Royal College of Physicians, 1998
http://www.show.scot.nhs.uk/sign/html/html24.htm
(Type V evidence – expert opinion)
iii.Gresham GE, Duncan PW, Stason WB, et al. Post-stroke rehabilitation. Clinical Practice Guideline Number 16 AHCPR. Rockville, MD: Agency for Health Care Policy and Research and the National Heart, Lung and Blood Institute, Public Health Service, U.S. Department of Health and Human Services, 1995
http://www.ahcpr.gov/clinic/
(Type V evidence – expert opinion)

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7.3 Drug therapy
7.3a. There is evidence to suggest antiplatelet therapy with aspirin in the acute phase of ischaemic stroke produces a small net benefit of 9 (SD 3) fewer deaths or non-fatal strokes per 1000 in the first few weeks (p=0.001) and 13 (SD 5) fewer dead or dependent per 1000 at follow-up of several months (p<0.01)i. Comparisons of heparin anticoagulant therapy vs. aspirin are inconclusiveii, however management with low-dose heparin (5000 IU) and aspirin in combination may be more effective than aspirin or heparin alone, and is more appropriate for patients in atrial fibrillation or with cardio-embolic strokeii.
(Health gain notation – 3 "trade-off between beneficial and adverse effects")
Caveat: The IST trialii was neither double blinded nor placebo controlled and anticoagulation monitoring was not systematic. CT scan was not an entry criterion and hence the comparisons of heparin vs. aspirin were subject to bias. Updated Cochrane Collaboration systematic reviews to include CASTi and ISTii in the meta-analyses are awaitediii,iv. Further trials to address the questions of benefit from antiplatelet and anticoagulant therapy (including standard and low-molecular weight heparins), singly or in combination, in precisely defined sub-groups of patients with acute ischaemic stroke are required.
i. CAST: randomised placebo-controlled trial of early aspirin use in 20 000 patients with acute ischaemic stroke. Lancet 1997;349:1641-49
(Type II evidence – randomised controlled trial of 21,106 patients within 48 hours of suspected ischaemic stroke treated with 160mg/day aspirin for up to four weeks)
ii. The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19 435 patients with acute ischaemic stroke. Lancet 1997;349:1569-81
(Type II evidence – randomised controlled trial of 19,435 patients within 48 hours of suspected ischaemic stroke in factorial design of 300mg/day aspirin, 5000 or 12,500 IU heparin twice daily for up to two weeks)
iii. Counsell C, Sandercock P. Antiplatelet therapy compared to control in acute presumed ischaemic stroke. Cochrane Review [Updated 19 August 1998]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 501 patients in five trials with six month follow-up plus narrative summary of references i and ii )
iv. Counsell C, Sandercock P. Anticoagulant therapy compared to control in patients with acute presumed ischaemic stroke. Cochrane Review [Updated 22 April 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 1599 patients in 15 trials)

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7.3b. There is no evidence that thrombolytic therapy in the acute phase of ischaemic stroke reduces mortality, morbidity or the risk of clinically important complications such as pulmonary embolism (excess mortality within the first two weeks – odds ratio 1.99; 95% CI: 1.56, 2.53 and during follow-up odds ratio 1.36; 95% CI: 1.14, 1.62). Despite the excess mortality, there was a trend in favour of thrombolytic therapy in the combined outcome of death or dependency at the end of follow-up (odds ratio 0.75; 95% CI: 0.63, 0.88)i. There are currently too few data to draw any reliable conclusions on the whether lower doses of different thrombolytic agents by different routes of administration are safer or more effective than higher dosesii.
(Health gain notation – 4 "unknown")
Caveat: Further trials are required, in which comparisons of thrombolytic therapy, antiplatelet and anticoagulant (standard and low-molecular weight heparins) therapy are made, and the sub-group of stroke patients most likely to benefit are assessed.
i. Wardlaw JM, Yamaguchi T, del Zoppo G. Thrombolytic therapy versus control in acute ischaemic stroke. Cochrane Review [Updated 12 August 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 3435 patients with CT/MRI proven acute ischaemic stroke in 12 trials)
ii. Liu M, Wardlaw J. Thrombolysis in acute ischaemic stroke: direct randomised comparisons of different doses, routes of administration and agents. Cochrane Review [updated 13 April 1998]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of seven trials including 725 patients)

 

7.3c. There is some evidence for the effectiveness of the methylxanthines pentoxifylline and propentofylline in the routine management of acute ischaemic stroke (non-significant reduction of odds of early death – odds ratio 0.64; 95% CI: 0.41, 1.02). No data on outcomes such as quality of life or stroke recurrence are availablei.
(Health gain notation – 4 "unknown")
Caveat: Primary trials randomised or quasi-randomised are too small and of insufficient quality to draw firm conclusions. A large randomised controlled trial to assess the efficacy and safety of pentoxifylline is required.
i. Bath PMW, Bath SJ, Asplund K. Pentoxifylline, propentofylline and pentifylline in acute ischaemic stroke. Cochrane Review [Updated 11 June 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 793 patients in five trials)

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7.3d. Current evidence suggests theophylline and aminophylline are not effective therapy in the management of acute ischaemic stroke (early case fatality or neurological deterioration was non-significantly reduced by 13%)i.
(Health gain notation – 4 "unknown")
Caveat: Insufficient patients have been studied. A large randomised controlled trial to assess the efficacy and safety of theophylline or analogues would be required although the present results do not suggest theophylline is likely to be very effectivei.
i. Mohiuddin AA, Bath FJ, Bath PMW. Theophylline, aminophylline, caffeine and analogues in acute stroke. Cochrane Review [Updated 2 June 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 119 patients in two trials)
7.3e. Current evidence suggests haemodilution is not an effective treatment for acute ischaemic stroke (odds ratio for dead/dependent/institutionalised 1.03; 95% CI: 0.87, 1.22). This conclusion concerns both hyper- and iso-volaemic haemodilution regimens and all types of haemodiluting agents used (dextran, hydroxyethyl starch and albumin)i.
(Health gain notation – 6 "likely to be ineffective")
i. Asplund K, Israelsson K, Schampi I. Haemodilution in acute ischaemic stroke. Cochrane Review [Updated 9 July 1995]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 2756 patients in 15 trials)
7.3f. The balance of benefit and risk from the routine use of vasoactive drugs in acute stroke is uncleari.
(Health gain notation – 4 "unknown")

Caveat: Insufficient numbers of patients have been studied in trials to assess the effect of changing blood pressure on clinical outcomes in patients with acute stroke.

i. Blood pressure in Acute Stroke Collaboration (BASC). Blood pressure management in acute stroke. Part I: assessment of trials designed to alter blood pressure. Cochrane Review [Updated 4 May 1997]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 133 patients in three trials)

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7.3g. There is little evidence for the effectiveness of glycerol treatment in acute ischaemic stroke. Short-term (two week) case fatality showed a 37% reduction in odds of death (95% CI: 9%, 64%) and a long-term death reduction of 18% (95% CI: 23%, 46%)i.
(Health gain notation – 4 "unknown")
Caveat: Studies have too few patients to determine effects and in some methods of randomisation are unclear. Attention also needs to be given to other outcomes such as quality of life and long term handicap as well as survival.
i. a’Rogvi-Hansen B, Boysen G. Glycerol treatment in acute ischaemic stroke. Cochrane Review [Updated 10 February 1994]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 254 patients in eight trials)
7.3h. There is no evidence that nimodipine and other calcium antagonists are effective in improving independence (Barthel index 60 and over at six-months) in patients with acute ischaemic strokei.
(Health gain notation – 4 "unknown")
i. Trust Study Group. Randomised, double-blind, placebo-controlled trial of minodipine in acute stroke. Lancet 1990; 336:1205-09
(Type II evidence – randomised controlled trial of 1215 patients randomised to 120mg oral nimodipine daily or placebo)
7.3i. There is insufficient evidence that prostacyclin is effective in the management of acute ischaemic stroke (odds ratio for early death 0.63; 95% CI: 0.22, 1.85)i.
(Health gain notation – 4 "unknown")
Caveat: Insufficient numbers of patients have been studied. A large randomised controlled trial is required.
i. Bath P, Bath F. Prostacyclin and analogues in acute ischaemic stroke. Cochrane Review [Updated 11 January 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence – systematic review and meta-analysis of 191 patients with presumed ischaemic stroke in five trials)

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7.3j. There is insufficient evidence to support the use of fibrinogen depleting agents in the treatment of acute ischaemic strokei.
(Health gain notation - 4 "unknown")
Caveat: There have been too few patients and outcome events to draw any reliable conclusions from the present studies.
i. Liu M, Counsell C, Wardlaw J. Fibrinogen depleting agents in acute ischaemic stroke. Cochrane Review [Updated 1 November 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 182 patients in three trials)
7.3k. A Cochrane Review to determine the effectiveness and safety of preventing venous thromboembolism in patients with cerebral haemorrhage is due for publication in 1999i.
(Health gain notation - 4 "unknown")
i. Feigin VL, Rinkel GJE, Algra A, van Gijn J. Standard heparin, heparinoids, or low-molecular weight heparin in the treatment of patients with primary intracerebral haemorrage. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis)
7.3l. There is insufficient evidence to support the use of corticosteroids in the routine management of acute ischaemic stroke. Analysis of case fatality found an 8% increase in the odds of death (95% CI: 72% increase to 32% reduction)i.
(Health gain notation - 4 "unknown")
Caveat: Further assessment of mega-dose corticosteroids in large infarcts with cerebral oedema required.
i. Qizilbash N, Lewington SL, Lopez-Arrieta JM. Corticosteroids following acute presumed ischaemic stroke. Cochrane Review [Updated 10 January 1997]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 453 patients with definite or presumed ischaemic stroke in seven trials)

 

7.3m. A Cochrane Review to determine whether treatment with mannitol reduces short and long-term mortality and dependency following ischaemic stroke or cerebral parenchymal haemorrhage is due for publication in 19991.
(Health gain notation - 4 "unknown")
i. Bereczki D, Liu M, do Prado GF, Fekete I. Mannitol in acute ischaemic stroke and cerebral parenchymal haemorrhage. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis)

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7.4 Secondary prevention
7.4a. Long-term antiplatelet therapy in patients with previous stroke/TIA is associated with reduced MI, stroke and vascular mortality at three year follow-up (% odds reduction 22% (SD 4), risk reduction 37
(SD 8)/1000 patients treated, p<0.000, NNT=26) and a significant reduction in non-fatal MI (% odds reduction 36% (SD 11), 9 (SD 3)/1000, p<0.000, NNT=100) and non-fatal stroke (% odds reduction 23% (SD 6), 20 (SD 6)/1000, p<0.000, NNT=50). Medium dose aspirin (75-325mg) is the most widely tested antiplatelet regimen and no other regimen appears to have a greater protective effect. Higher doses are associated with increased adverse eventsi. Other antiplatelet drugs, either alone or in combination with aspirin, have not been shown to be more effective than aspirin alonei. However more recent evidence suggests a synergistic benefit of aspirin with dipyridamole in the risk of stroke or deathii,iii; dipyridamole may be better tolerated than aspirin.
(Health gain notation - 1 "beneficial")
i. Antiplatelet Trialist's Collaboration. Collaborative overview of randomised trials of antiplatelet therapy - I: Prevention of death, myocardial infarction and stroke by prolonged antiplatelet therapy in various categories of patients. British Medical Journal 1994;308:81-106.
http://www.bmj.com/cgi/content/full/308/6943/1540
In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and sub-group meta-analysis of 11,707 patients with previous stroke/TIA in 18 trials of antiplatelet therapy)
ii. Lowenthal A, Buyse M. Secondary prevention of stroke: does dipyridamole add to aspirin? Acta Neurologica Belgica 1994;94:24-34. In: Database of Reviews of Effectiveness. The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 7666 patients in treatment groups and 3776 in placebo groups)
iii. Diener HC, Cunha L, Forbes C, Sivenius J, Smets P, Lowenthal A. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. Journal of Neurological Science 1996;143:1-13
(Type II evidence - randomised controlled secondary prevention trial of 6602 patients in a 2 2 factorial design involving 50 mg aspirin and 400mg dipyridamole daily)
7.4b. Clopidogrel may be more effective than aspirin in the secondary prevention of non-fatal ischaemic stroke, non-fatal MI, or vascular death (the CAPRIE composite primary outcome) in patients with recent ischaemic stroke, MI, or symptomatic peripheral vascular disease: 5.32% vs. 5.83%; relative risk reduction 8.7%; 95% CI: 0.3, 16.5; p=0.043. No benefit was found for the secondary outcomes of vascular death alone or death from any cause. No major differences in safety were showni.
(Health gain notation - 2 "likely to be beneficial")
Caveat: Significant benefit of clopidogrel was only found for the protocol specified primary outcome. No benefit was shown for clopidogrel over aspirin in the four protocol specified secondary outcomes, including vascular and all-cause mortality. Sub-group analysis found significant heterogeneity between the three patient sub-groups, with significant benefit shown only in patients with previous history of peripheral vascular disease. Further trials and evidence of greater cost-effectiveness is required before the use of clopidogrel is justified over aspirin either alone or in combination with dipyridamole.
i. CAPRIE steering committee. A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39
(Type II evidence - randomised controlled trial of 19,185 patients, mean 1.9 year follow-up)

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7.4c. A Cochrane Review to determine the relative effectiveness and safety of ticlopidine and clopidogrel compared to aspirin in the secondary prevention of stroke and other important vascular outcomes in patients at high risk (previous TIA, ischaemic stroke, MI and peripheral vascular disease) is due for publication in 19991.
(Health gain notation - 4 "unknown")
i. Hankey GJ, Dunbabin DW, Sudlow CLM. Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin in the secondary prevention of stroke and other important vascular events among high risk patients. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis)
7.5 Anticoagulation
7.5a. Anticoagulation of patients with non-rheumatic atrial fibrillation within three months of a transient ischaemic attack or minor ischaemic stroke reduces the risk of serious vascular events at two year follow-up compared to controli (all major vascular events, odds ratio 0.55; 95% CI: 0.37, 0.82: recurrent stroke odds ratio 0.36; 95% CI: 0.22, 0.58), and compared to aspirinii (all major vascular events, odds ratio 0.55; 95% CI: 0.36, 0.83: recurrent stroke odds ratio 0.36; 95% CI: 0.22, 0.59). Anticoagulation is associated with a higher risk of major bleeding complications (odds ratio 4.65; 95% CI: 1.66, 12.99)i.
(Health gain notation - 1 "beneficial")
i. Koudstaal P. Secondary prevention following stroke or transient ischaemic attack in patients with non-rheumatic atrial fibrillation: anticoagulant versus control. Cochrane Review [Updated 14 February 1995]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type II evidence - systematic review of two randomised controlled trials randomising 1053 patients to open label anticoagulants or placebo)
ii. Koudstaal P. Secondary prevention following stroke or transient ischaemic attack in patients with non-rheumatic atrial fibrillation: anticoagulant versus antiplatelet therapy. Cochrane Review [Updated 15 February 1995]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type II evidence - systematic review of one randomised controlled trial randomising 455 patients to open label anticoagulants or 300mg aspirin)

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7.5b. There is no clear evidence of benefit from anticoagulation of patients not in atrial fibrillation with acute non-embolic ischaemic stroke or transient ischaemic attack (odds ratio for death or dependency 0.83; 95% CI: 0.52, 1.34). Anticoagulation is associated with a higher risk of major bleeding complications (odds ratio for fatal intracranial haemorrhage 2.54; 95% CI: 1.19, 5.45; and fatal extracranial haemorrhage 4.87; 95% CI: 2.50, 9.49)i.
(Health gain notation - 4 "unknown")
Caveat: Poor methodological quality of old pre-1975 primary studies. Further trials to assess the differential and combination effects of aspirin and anticoagulation in both the acute phase and secondary prevention of non-haemorrhagic stroke in patients not in atrial fibrillation are required.
i. Liu M, Counsell C, Sandercock P. Anticoagulation versus no anticoagulation following non-embolic ischaemic stroke or TIA. Cochrane Review [Updated 10 September 1997]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 1214 patients in nine trials comparing at least one month anticoagulation with placebo)
7.5c. Control of anticoagulation therapy can be satisfactorily achieved within General Practice, which offers the advantages of increased convenience and access for patients and continuity of carei.
(Health gain notation - 2 "likely to beneficial")
i. Anon. Anticoagulant therapy in General Practice. Welsh Medicines Resource Centre Bulletin 1997;4:3 Penarth: WeMeReC, 1997
(Type V evidence - expert opinion)
7.6 Carotid imaging
7.6a. Non-invasive imaging with carotid duplex ultrasonography is the first line investigation of carotid disease and can reliably select lesions appropriate for surgery only when critical stenosis of >70%i or >80%ii is present. Routine angiography is recommended for carotid stenosis of 50-70% when carotid endarterectomy is consideredi,ii.. The safety and effectiveness of performing carotid surgery on the basis of ultrasonography alone has not been formally demonstratediii.
(Health gain notation - 2 " likely to be beneficial")
i. Eliasziw M, Rankin RN, Fox AJ, Haynes RB, Barnett HJM and the North American Symtomatic Carotid Endarterectomy Trial (NASCET) Group. Accuracy and prognostic consequences of ultrasonography in identifying severe carotid artery stenosis. Stroke 1995; 26(10):1747-52
(Type IV evidence - validation of ultrasonography findings against angiography performed on 1011 carotid bifurcations in the NASCET trial)
ii. Chen JC, Salvian AJ, Taylor DC, Teal PA, Marotta TR, and Hsiang YN. Can duplex ultrasonography select appropriate patients for carotid endarterectomy? European Journal of Vascular and Endovascular Surgery 14 (6): 451-56
(Type IV evidence - prospective study of 145 carotid arteries in 102 patients comparing carotid duplex ultrasound with digital subtraction angiography)
iii. Scottish Intercollegiate Guidelines Network (SIGN). Management of Patients with Stroke II: Management of Carotid Stenosis and Carotid Endarterectomy Assessment, Investigation, Immediate Management and Secondary Prevention. Edinburgh: Royal College of Physicians, 1997 http://www.show.scot.nhs.uk/sign/pdf/sign14.pdf
[Adobe Acrobat reader required]
(Type V evidence - expert opinion)

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7.6b. Magnetic resonance imaging (MRI) with contrast enhancement in combination with duplex ultrasonography has greater sensitivity and specificity than angiography in the assessment of carotid stenosisi,ii.

(Health gain notation - 2 "likely to be beneficial")

i. Young GR, Humphrey PRD, Shaw MDM, Nixon TE, Smith ETS. Comparison of magnetic resonance angiography, duplex ultrasound and digital subtraction angiography in assessment of extracranial internal carotid artery stenosis. Journal of Neurology and Neurosurgical Psychiatry 1994;57:1466-78
(Type III evidence - non-randomised prospective comparison study of 137 arteries in 70 patients)
ii. Patel MR, Kuntz KM, Klufas RA, et al. Preoperative assessment of the carotid bifurcation. Can magnetic resonance angiography and duplex ultrasonography replace contrast arteriography? Stroke 1995;26:1753-58
(Type III evidence - non-randomised prospective comparison study of 176 carotid arteries in 88 patients)
7.6c. Carotid bruits have low sensitivity (36%), specificity (71%) and positive predictive value (68%) in the diagnosis of carotid stenosisi.
(Health gain notation - 5 "unlikely to be beneficial")
i. Davies KN. Do carotid bruits predict disease of the internal carotid arteries? Postgraduate Medical Journal 1994;70:433-35
(Type III evidence - non-randomised prospective study of 331 patients comparing clinical examination and duplex scanning)
7.7 Carotid endarterectomy
7.7a. Symptomatic patients with severe carotid stenosis (ECST 80% and overi) benefit from a reduced risk of stroke following carotid endarterectomyi,ii; three-year risk of any major stroke or death; surgery 14.9% vs. control 26.5%; overall difference 11.6%, p=0.001i. The downwards trend in benefit of surgery from 100% stenosis suggests patients with stenosis of between 70% and 80% may benefit depending on patient factors and the risk of surgeryi.
(Health gain notation - 1 "beneficial")
i. European Carotid Surgery Trialists’(ECST) Collaborative Group. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet 1998;351:1379-87
(Type II evidence - randomised control trial of 3024 patients with mean 6.1 year follow-up)
ii. North American Symptomatic Carotid Enderterectomy Trial (NASCET) Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. New England Journal of Medicine 1991;325:445-53
(Type II evidence - randomised controlled trial of 659 patients with >70% stenosis)
iii. Asymptomatic Carotid Atherosclerosis Study (ACAS). Endarterectomy for Asymptomatic Carotid Artery Stenosis. Journal of the American Medical Association 1995;273:1421-28
(Type II evidence - randomised controlled trial of 1659 patients with >60% stenosis receiving aspirin median follow-up 2.7 years)
iv. Risk of stroke in the distribution of an asymptomatic carotid artery. Lancet 1995;345:209-12
(Type II evidence - 4.5 year mean follow-up of 2695 patients with >60% stenosis receiving aspirin randomised in the ECST trial)
7.7b. Carotid endarterectomy has not been shown to be effective in patients with mild or moderate carotid stenosis (ECST<70%)i.
(Health gain notation - 5 "unlikely to be beneficial")
7.7c. Carotid endarterectomy for asymptomatic carotid stenosis of >60% is associated with a risk reduction for ipsilateral stroke or peri-operative stroke or death of 53% (95% CI: 22%, 72%)iii. Overall benefit is only achieved when perioperative morbidity and mortality is less than 3%. Because the incidence of stroke in these patients is small (three year incidence of all stoke<5%)iv, carotid endarterectomy should only be performed in the context of randomised controlled trialsiii.
(Health gain notation - 4 "unknown")
 

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7.7d. There is insufficient data from randomised controlled trials to recommend the routine use of local anaesthesia for carotid endarterectomyi.
(Health gain notation - 4 "unknown")
Caveat: The non-randomised studies showed local anaesthesia was associated with significant reductions in the odds of stroke and death. Large well designed randomised controlled trials are required.
i. Tangkanakul C, Counsell C, Warlow C. Carotid endarterectomy performed under local anaesthetic compared to general anaesthetic. Cochrane Review [Updated 2 August 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review of 143 patients in three small trials and 17 non-randomised trials)
7.7e. A Cochrane Review of the risks and benefits of carotid endarterectomy in adult patients with ipsilateral symptomatic carotid stenosis is due for publication in 1999i.
(Health gain notation - 4 "unknown")
i. Cina CS, Clase CM, Haynes RB. Carotid endarterectomy in patients with symptomatic carotid stenosis. Protocol for a Cochrane Review. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis)
7.7f. Evidence-based guidelines for carotid endarterectomy are availablei.
(Health gain notation - 1 "beneficial")
i. Biller J, Feinberg WM, Castaldo JE, et al. Guidelines for carotid endarterectomy: a statement for healthcare professionals from a special writing group of the stroke council, American Heart Association. Stroke 1998;29:554-62
http://www.americanheart.org/Scientific/statements/
1998/029801.html

(Type V evidence - expert opinion)

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7.7g. There is insufficient randomised controlled trial evidence to support the use of routine shunting in carotid endarterectomy (for death or stroke within 30 days, results show non-significant trends favouring shunting)i.
(Health gain notation - 4 "unknown")
Caveat: Original trials were poorly randomised, with short duration of follow up and some important outcomes were not measured.
i. Counsell C, Salinas R, Naylor R, Warlow C. Routine or selective carotid artery shunting during carotid endarterectomy and the different methods of monitoring in selective shunting. Cochrane Review [Updated 8 December 1994]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 721 patients in three trials)
7.7h. There is insufficient evidence at present to support the use of carotid patching compared to primary closure during endarterectomyi. No evidence supports the use of one patch compared to anotherii.
(Health gain notation - 4 "unknown")
Caveat: There were too few events in poor quality trials during the perioperative period to determine whether there were significant differences between the patch materials.
i. Counsell C, Salinas R, Warlow C, Naylor R. Patch angioplasty compared to primary closure in carotid endarterectomy. Cochrane Review [Updated 17 May 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 882 operations in six trials)
ii. Counsell C, Warlow C, Naylor R. A comparison of different types of patch in carotid patch angioplasty. Cochrane Review [Updated 17 May 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 326 operations in three trials)

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7.7i. There is no randomised controlled trial evidence to date to support a change in the routine clinical treatment of patients with carotid stenosis to percutaneous transluminal angioplasty, with or without stentingi,ii.
(Health gain notation - 4 "unknown")
Caveat: No completed randomised controlled trials identified. The Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS) is in progressiii.
i. Crawley F, Brown MM. Percutaneous transluminal angioplasty and stenting for treatment of carotid artery stenosis. Cochrane Review [Updated 21 July 1997]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type III evidence - non-randomised studies)
ii. Bettmann MA, Katzen BT, Whisnant J, et al. Carotid stenting and angioplasty: a statement for healthcare professionals from the councils on cardiovascular radiology, stroke, cardio-thoracic and vascular surgery, epidemiology and prevention, and clinical cardiology, American Heart Association. Circulation 1998;97:121-23
http://www.americanheart.org/Scientific/statements/
1998/019801.html

(Type V evidence - expert opinion)
iii. Sivaguru A, Venables GS, Beard JD, Gaines PA. European carotid angioplasty trial. Journal of Endovascular Surgery 1996;3:16-20
(Type II evidence - randomised controlled trial)
7.8 Other surgical management of stroke
7.8a. Surgery for intracerebral haematoma has not been shown to be effective (odds ratio of craniotomy for death or dependence 1.99; 99% CI: 0.92, 4.31; and odds ratio for endoscopic evacuation 0.45; 99% CI: 0.15, 1.33)i.
(Health gain notation - 4 "unknown")
Caveat: The role of craniotomy and stereotactic surgery has not been adequately studied in randomised trials.
i. Prasad K, Shrivastava A. Surgical treatment in patients with primary supratentorial intracerebral haemorrhage. Cochrane Review [Updated 11 November 1996]. In: The Cochrane Library, Issue 4. Oxford: Update Software, 1998
(Type I evidence - systematic review and meta-analysis of 354 patients in four trials)

 

7.8b. There is no evidence for the effectiveness of extracranial-intracranial arterial anastomosis (EC/IC bypass) in patients with transient ischaemic attack or stroke not amenable to carotid endarterectomyi.
(Health gain notation - 5 "unlikely to be beneficial")
i. Haynes RB, Mukherjee J, Sackett DL, Taylor DW, Barnett HJ, Peerless SJ, for the EC/IC Bypass Study Group. Functional status changes following medical or surgical treatment for cerebral ischaemia. Results of the extracranial-intracranial bypass study. Journal of the American Medical Association 1987;257:2043-46
(Type II evidence - randomised controlled trial of 1377 patients)
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Health Evidence Bulletins: Wales, Duthie Library, UWCM, Cardiff CF14 4XN. e-mail: weightmanal@cardiff.ac.uk