Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic

Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999 282 2019-2026 [see comment]. 

OR 1.81, 95% Cl 1.46-2.24), most of which were related to symptomatic intracranial hemorrhage (OR 3.37, 95% Cl 2.68. 22). In addition, a pooled analysis of six major randomized placebo-controlled IV rt-PA stroke trials (Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) I and II, European Cooperative Acute Stroke Study (ECASS) I and II, and NINDS I and II), including 2775 patients who were treated with IV rt-PA or placebo within 360 minutes of stroke onset, confirmed the beneht up to 3 hours and suggested a potential beneht beyond 3 hours for some patients. The pattern of a decreasing chance of a favorable 3-month outcome as the time interval from stroke onset to start of treatment increased was consistent with the findings of the original NINDS study. ... 

A pooled analysis of individual patient data from the NINDS, ECASS I and II and the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) trials (Hacke et al. 2004), which represents 99% of patients randomized in trials of rt-PA in stroke, has confirmed that benefit from thrombolysis decreases with time since stroke onset, being most beneficial if given within 90 minutes (odds ratio for favorable outcome of 2.8) (Fig. 21.1), although benefit was still present at 4.5 hours (now confirmed in ECASS III). However, it is clear that many patients will not benefit at this time point and, conversely, that other patients may benefit up to and beyond six hours in view of the fact that the ischemic penumbra may extend for much longer periods in some patients (Baron 2001). At present, only approximately 1% of UK patients receive thrombolysis (Intercollegiate Working Party on Stroke 2006) and 1-6% in North America. 

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