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

Andrei Alexandrov, Peter D. Schellinger, Maher Saqqur, Andrew Barreto, Andrew M. Demchuk, Marc Ribo, Marta Rubiera, Vijay K. Sharma, Ioannis Heliopoulos, Anne Alexandrov, Carlos A. Molina, Georgios Tsivgoulis

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Abstract

Background 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). 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 17·6 ± 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 2h later (2·3 ± 0·6 vs. 4·3 ± 1·5h; 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). 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.

Original languageEnglish (US)
Pages (from-to)118-122
Number of pages5
JournalInternational Journal of Stroke
Volume6
Issue number2
DOIs
StatePublished - Apr 1 2011

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Tissue Plasminogen Activator
Reperfusion
Myocardial Infarction
Clinical Trials
Intracranial Hemorrhages
Stroke
National Institutes of Health (U.S.)
Brain Ischemia
Plasminogen Activators
Thrombosis
Therapeutics
Control Groups
Mortality

All Science Journal Classification (ASJC) codes

  • Neurology

Cite this

Reperfusion and outcomes in Penumbra vs. systemic tissue plasminogen activator clinical trials. / Alexandrov, Andrei; Schellinger, Peter D.; Saqqur, Maher; Barreto, Andrew; Demchuk, Andrew M.; Ribo, Marc; Rubiera, Marta; Sharma, Vijay K.; Heliopoulos, Ioannis; Alexandrov, Anne; Molina, Carlos A.; Tsivgoulis, Georgios.

In: International Journal of Stroke, Vol. 6, No. 2, 01.04.2011, p. 118-122.

Research output: Contribution to journalArticle

Alexandrov, A, Schellinger, PD, Saqqur, M, Barreto, A, Demchuk, AM, Ribo, M, Rubiera, M, Sharma, VK, Heliopoulos, I, Alexandrov, A, Molina, CA & Tsivgoulis, G 2011, 'Reperfusion and outcomes in Penumbra vs. systemic tissue plasminogen activator clinical trials', International Journal of Stroke, vol. 6, no. 2, pp. 118-122. https://doi.org/10.1111/j.1747-4949.2010.00559.x
Alexandrov, Andrei ; Schellinger, Peter D. ; Saqqur, Maher ; Barreto, Andrew ; Demchuk, Andrew M. ; Ribo, Marc ; Rubiera, Marta ; Sharma, Vijay K. ; Heliopoulos, Ioannis ; Alexandrov, Anne ; Molina, Carlos A. ; Tsivgoulis, Georgios. / Reperfusion and outcomes in Penumbra vs. systemic tissue plasminogen activator clinical trials. In: International Journal of Stroke. 2011 ; Vol. 6, No. 2. pp. 118-122.
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abstract = "Background 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). 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 17·6 ± 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 2h later (2·3 ± 0·6 vs. 4·3 ± 1·5h; 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). 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.",
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T1 - Reperfusion and outcomes in Penumbra vs. systemic tissue plasminogen activator clinical trials

AU - Alexandrov, Andrei

AU - Schellinger, Peter D.

AU - Saqqur, Maher

AU - Barreto, Andrew

AU - Demchuk, Andrew M.

AU - Ribo, Marc

AU - Rubiera, Marta

AU - Sharma, Vijay K.

AU - Heliopoulos, Ioannis

AU - Alexandrov, Anne

AU - Molina, Carlos A.

AU - Tsivgoulis, Georgios

PY - 2011/4/1

Y1 - 2011/4/1

N2 - Background 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). 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 17·6 ± 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 2h later (2·3 ± 0·6 vs. 4·3 ± 1·5h; 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). 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.

AB - Background 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). 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 17·6 ± 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 2h later (2·3 ± 0·6 vs. 4·3 ± 1·5h; 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). 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.

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