Reperfusion and outcomes in Penumbra vs. systemic tissue plasminogen activator clinical trials.
Comprehensive Stroke Center, University of Alabama Hospital, Birmingham, AL 35249 3280, USA.
An uncontrolled clinical study of the Penumbra(™) system showed high rates of recanalisation and relatively poor functional outcomes that were inadequately compared with historic controls. We aimed to compare the findings in Penumbra with intravenous tissue plasminogen activator trials that determined recanalisation (Combined Lysis Of Thrombus in Brain ischaemia using transcranial Ultrasound and Systemic tissue plasminogen activator and Transcranial Ultrasound in Clinical Sonothrombolysis).
Control patients treated with intravenous tissue plasminogen activator and intermittent ultrasound surveillance had National Institutes of Health Stroke Scale scores >7. The Penumbra trial definition of symptomatic intracranial haemorrhage was used. Revascularisation was defined using thrombolysis in brain ischaemia scores predictive of thrombolysis in myocardial infarction flow grades and compared with thrombolysis in myocardial infarction data from Penumbra. Favourable functional outcomes was defined as a modified Rankin Scale of 0-2.
Pretreatment stroke severity (National Institutes of Health Stroke Scale score) was 17.6 ± 5.2 points in Penumbra patients (n = 125) and 16.3 ± 5.3 in controls (n = 68; P = 0.101). The control group was older compared with Penumbra (68.8 ± 13.4 vs. 63.5 ± 13.5-years; P = 0.010). Time-to-treatment initiation was on average 2 h later (2.3 ± 0.6 vs. 4.3 ± 1.5 h; P < 0.001) in Penumbra. The rate of any revascularisation after treatment with Penumbra was higher than that following intravenous thrombolysis: 82% (54% thrombolysis in myocardial infarction II and 27% thrombolysis in myocardial infarction III) vs. 40% (25% partial, 15% complete revascularisation), P < 0.001. Symptomatic intracranial haemorrhage tended to be higher with Penumbra (11.2% vs. 4.4%; P = 0.182, Fisher's exact test). At three-months, mortality with Penumbra was higher (32.8%) than controls (14.1%; P = 0.006). Favourable functional outcomes were higher in historic controls (39% vs. 25%; P = 0.046).
Despite lower revascularisation rates, patients treated with systemic thrombolysis achieved better functional outcomes likely due to earlier treatment initiation. These data indicate that it is unrealistic to expect primary intraarterial revascularisation to be any better than systemic plasminogen activator within the 3-h time window. Improvements in the speed of delivery and performance of intraarterial reperfusion are needed.
© 2010 The Authors. International Journal of Stroke © 2010 World Stroke Organization.