Beneficial

• Stroke units
  A Cochrane systematic review identified 20 RCTs in 3,864 people with stroke comparing specialised stroke units versus conventional care. In most trials, the specialised stroke unit consisted of a designated area or ward, although some trials used a mobile 'stroke team'.
  • Those cared for in a stroke unit had lower rates of death or dependency after a median follow up of one year (RRR 10%, 95% CI 5% to 15%; NNT=16, 95% CI 10 to 43).
  • Overall, the length of stay in the stroke unit group was reduced by about 2 to 11 days.

  (Source: Stroke Unit Trialists' Collaboration. Organised inpatient (stroke unit) care for stroke. In: The Cochrane Library (Online), Issue 2, 2000. Oxford: Update Software.)

• Aspirin
  A systematic review of "eight RCTs comparing antiplatelet treatment started within 14 days of the stroke versus placebo in 41,325 people with definite or presumed ischaemic stroke was identified. 98% of the data in the systematic review came from two large RCTs testing aspirin 160 to 300 mg daily started within 48 hours of stroke onset. Most patients had an ischaemic stroke confirmed by CT scan before randomisation, but those who were conscious could be randomised before CT scan if the stroke was very likely to be ischaemic on clinical grounds. Treatment duration varied from 10 to 28 days. Aspirin started within the first 48 hours of acute ischaemic stroke reduced death and dependency at follow up (RRR 3%, 95% CI 1% to 5%; NNT=77, 95% CI 43 to 333)."
  {Source: Gubitz G, Sandercock P. Stroke: Management. Clinical Evidence 1999;2:104-12}

Trade off between benefits and harms

• Thrombolysis
  A Cochrane systematic review of 17 RCTs with 5,216 highly selected patients was identified. All trials included a CT or magnetic resonance scan to exclude intracranial haemorrhagic or other non-stroke disorders. The trials tested urokinase, streptokinase, recombinant tissue plasminogen activator or recombinant pro-urokinase.
  • Thrombolysis reduced the risk of being dead or dependent at the end of the studies (ARR 4.2%, 95% CI 1.2% to 7.2%; RRR 7%, 95% CI 3% to 12%; NNT=24, 95% CI 14 to 83).
  • Thrombolytic therapy administered up to six hours after ischaemic stroke significantly reduced the proportion of patients who were dead or dependent at the end of follow up (OR 0.83, 95% CI 0.73 to 0.94).
    For patients treated within three hours of stroke, thrombolytic therapy appeared to be more effective in reducing death or dependency (OR 0.58, 95% CI 0.46 to 0.74) with less adverse effect on death (OR 1.11, 95% CI 0.84 to 1.47).
  • Thrombolysis increased fatal intracranial haemorrhage compared with placebo (ARI 4.4%, 95% CI 3.4% to 5.4%; RRI 396%, 95% CI 220% to 668%; NNH=23, 95% CI 19 to 29).
  • Thrombolytic treatment increased the risk of death by the end of the follow up period compared with placebo (ARI 3.3%, 95% CI 1.2% to 5.4%; RRI 23%, 95% CI 10% to 28%; NNH=30, 95% CI 19 to 83). This excess of deaths was offset by fewer people being alive but dependent six months after stroke onset. The net effect was a reduction in the number of people who were dead or dependent.

  (Source: Wardlaw JM, del Zoppo G, Yamaguchi T. Thrombolysis for acute ischaemic stroke. In: The Cochrane Library (Online), Issue 2, 2000. Oxford: Update Software. [Last amendment: 21 Feb, 2000.])

Likely to be ineffective or harmful

• Immediate systematic anticoagulation
  A Cochrane systematic reviews of 21 RCTs involving 23,427 patients comparing standard unfractionated heparin, low-molecular-weight heparins, heparinoids, anticoagulants or thrombin inhibitors versus control was identified.
  • No significant difference in the proportion of people dead or dependent in the treatment or control groups at the end of follow up (3 to 6 months after stroke, ARR 0.4%, 95% CI -0.9% to +1.7%; RRR 0%, 95% CI -2% to +3%). Majority of the patient data (90%) came from a single trial evaluating unfractionated heparin [IST 1997]. However, data from trials of low molecular weight heparin [FISS 1995, FISS-bis 1998] (OR=0.85, 95% CI 0.66 to 1.10), and heparinoid [TOAST 1999] (OR=0.92, 95% CI 0.72 to 1.19), also showed no clear evidence of benefit.

  [Editorial note: FISS and FISS-bis showed conflicting results; FISS study revealed that high dose fraxiparine significantly lowered the risk of death or dependency at 6 months (45%) compared to placebo (65%; p=0.005) whereas no evidence of benefits were seen in the FISS-bis study.]

  • Reduced the risk of deep vein thrombosis (ARR 29%, 95% CI 24% to 35%; RRR 64%, 95% CI 54% to 71%; NNT=3, 95% CI 2 to 4).
  • Reduced the development of symptomatic pulmonary embolism (ARR 0.3%, 95% CI 0.1% to 0.6%; RRR 38%, 95% CI 16% to 54%; NNT=333, 95% CI 167 to 1000).
  • Increased intracranial haemorrhages within 14 days of starting treatment (ARI 0.93%, 95% CI 0.68% to 1.18%; RRI 163%, 95% CI 95% to 255%; NNH=108, 95% CI 85 to 147). There is a dose dependent increase in both intra- and extracranial haemorrhage, although low dose regimens decrease deep vein thrombosis and pulmonary embolus (which can be treated with aspirin or compression stockings).

  The reviewers concluded that "immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long term benefit. The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke."

  (Sources: Gubitz G, Counsell C, Sandercock P, Signorini D. Anticoagulants for acute ischaemic stroke. In: The Cochrane Library (Online), Issue 2, 2000. Oxford: Update Software; International Stroke Trial Collaborative Group. 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(9065):1569-81; (FISS) Kay R, Wong KS, Yu YL, Chan YW, Tsoi TH, Ahujai AT et al. Low-molecular-weight heparin for the treatment of acute ischaemic stroke. N Eng J Med 1995 Dec 14;333(24):1588-93; Hommel M, for the FISS-bis Investigator Group. Fraxiparine in Ischaemic Stroke Study (FISS-bis) Cerebrovasc Dis 1998;8(suppl 4) 19; Adams HP, Bendixen BH, Leira E, Chang KC, Davis PH, Woolson RF et al. Antithrombotic treatment of ischemic stroke among patients with occlusion or severe stenosis of the internal carotid artery: A report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology 1999 Jul 13;53(1):122-5.}

• Acute reduction in blood pressure
  • A Cochrane systematic review of 3 RCTs comparing blood pressure lowering treatment versus placebo in 113 patients with acute stroke found insufficient evidence to evaluate the effect of altering blood pressure after stroke.

  (Source: Blood pressure in Acute Stroke Collaboration (BASC). Interventions for deliberately altering blood pressure in acute stroke. In: The Cochrane Library (Online), Issue 2, 2000. Oxford: Update Software.)

8 Feb 2000