03323nas a2200217   4500000000100000008004100001260001700042100001500059700001400074700001300088700001700101700001800118700001500136700001300151245012000164250001500284300001200299490000800311520274000319020004603059       2012                            d  c-357579231641 aWardlaw J.1 aMurray V.1 aBerge E.1 adel Zoppo G.1 aSandercock P.1 aLindley R.1 aCohen G.00aRecombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis  a2012/05/29  a2364-720 v3793 a<p>
BACKGROUND: Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in patients treated soon after acute ischaemic stroke in randomised trials, but licensing is restrictive and use varies widely. The IST-3 trial adds substantial new data. We therefore assessed all the evidence from randomised trials for rt-PA in acute ischaemic stroke in an updated systematic review and meta-analysis. METHODS: We searched for randomised trials of intravenous rt-PA versus control given within 6 h of onset of acute ischaemic stroke up to March 30, 2012. We estimated summary odds ratios (ORs) and 95% CI in the primary analysis for prespecified outcomes within 7 days and at the final follow-up of all patients treated up to 6 h after stroke. FINDINGS: In up to 12 trials (7012 patients), rt-PA given within 6 h of stroke significantly increased the odds of being alive and independent (modified Rankin Scale, mRS 0-2) at final follow-up (1611/3483 [46.3%] vs 1434/3404 [42.1%], OR 1.17, 95% CI 1.06-1.29; p=0.001), absolute increase of 42 (19-66) per 1000 people treated, and favourable outcome (mRS 0-1) absolute increase of 55 (95% CI 33-77) per 1000. The benefit of rt-PA was greatest in patients treated within 3 h (mRS 0-2, 365/896 [40.7%] vs 280/883 [31.7%], 1.53, 1.26-1.86, p&lt;0.0001), absolute benefit of 90 (46-135) per 1000 people treated, and mRS 0-1 (283/896 [31.6%] vs 202/883 [22.9%], 1.61, 1.30-1.90; p&lt;0.0001), absolute benefit 87 (46-128) per 1000 treated. Numbers of deaths within 7 days were increased (250/2807 [8.9%] vs 174/2728 [6.4%], 1.44, 1.18-1.76; p=0.0003), but by final follow-up the excess was no longer significant (679/3548 [19.1%] vs 640/3464 [18.5%], 1.06, 0.94-1.20; p=0.33). Symptomatic intracranial haemorrhage (272/3548 [7.7%] vs 63/3463 [1.8%], 3.72, 2.98-4.64; p&lt;0.0001) accounted for most of the early excess deaths. Patients older than 80 years achieved similar benefit to those aged 80 years or younger, particularly when treated early. INTERPRETATION: The evidence indicates that intravenous rt-PA increased the proportion of patients who were alive with favourable outcome and alive and independent at final follow-up. The data strengthen previous evidence to treat patients as early as possible after acute ischaemic stroke, although some patients might benefit up to 6 h after stroke. FUNDING: UK Medical Research Council, Stroke Association, University of Edinburgh, National Health Service Health Technology Assessment Programme, Swedish Heart-Lung Fund, AFA Insurances Stockholm (Arbetsmarknadens Partners Forsakringsbolag), Karolinska Institute, Marianne and Marcus Wallenberg Foundation, Research Council of Norway, Oslo University Hospital.
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