Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis
The Lancet - Early Online Publication, 05/31/2012
Evidence Based Medicine
Clinical Article
Wardlaw JM et al. - The evidence indicates that intravenous Recombinant tissue plasminogen activator (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.
Methods- The authors 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.
- The authors 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.
- 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<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<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<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.
