Reperfusion and outcomes in Penumbra vs. systemic tissue plasminogen activator clinical trials

Background An uncontrolled clinical study of the Penumbra (TM) 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). Methods 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. Results Pretreatment stroke severity (National Institutes of Health Stroke Scale score) was 17 center dot 6 +/- 5 center dot 2 points in Penumbra patients (n=125) and 16 center dot 3 +/- 5 center dot 3 in controls (n=68; P=0 center dot 101). The control group was older compared with Penumbra (68 center dot 8 +/- 13 center dot 4 vs. 63 center dot 5 +/- 13 center dot 5-years; P=0 center dot 010). Time-to-treatment initiation was on average 2 h later (2 center dot 3 +/- 0 center dot 6 vs. 4 center dot 3 +/- 1 center dot 5 h; P < 0 center dot 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 center dot 001. Symptomatic intracranial haemorrhage tended to be higher with Penumbra (11 center dot 2% vs. 4 center dot 4%; P=0 center dot 182, Fisher's exact test). At three-months, mortality with Penumbra was higher (32 center dot 8%) than controls (14 center dot 1%; P=0 center dot 006). Favourable functional outcomes were higher in historic controls (39% vs. 25%; P=0 center dot 046). Conclusions 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.