Greater effect of stroke thrombolysis in the presence of arterial obstruction.
OBJECTIVE
Recanalization of arterial obstruction is associated with improved clinical outcomes. There are no controlled data demonstrating whether arterial obstruction status predicts the treatment effect of intravenous (IV) tissue plasminogen activator (tPA). We aimed to determine if the presence of arterial obstruction improves the treatment effect of IV tPA over placebo in attenuating infarct growth.


METHODS
We analyzed 175 ischemic stroke patients treated in the 3-6 hour time window from the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) trial (randomized to IV tPA or placebo) and Diffusion and perfusion imaging Evaluation For Understanding Stroke Evolution (DEFUSE) study (all treated with IV tPA). Infarct growth was calculated as the difference between baseline diffusion-weighted imaging (DWI) and final T2 lesion volumes. Baseline arterial obstruction of large intracranial arteries was graded on magnetic resonance angiography (MRA).


RESULTS
Among the 116 patients with adequate baseline MRA and final lesion assessment, 72 had arterial obstruction (48 tPA, 24 placebo) and 44 no arterial obstruction (33 tPA, 11 placebo). Infarct growth was lower in the tPA than placebo group (median difference 26ml, 95% confidence interval [CI], 1-50) in patients with arterial obstruction, but was similar in patients with no arterial obstruction (median difference 5ml, 95%CI, -3 to 9). Infarct growth attenuation with tPA over placebo treatment was greater among patients with arterial obstruction than those without arterial obstruction by a median of 32ml (95%CI, 21-43, p < 0.001).


CONCLUSIONS
The treatment effect of IV tPA over placebo was greater with baseline arterial obstruction, supporting arterial obstruction status as a consideration in selecting patients more likely to benefit from IV thrombolysis.
Department of Neurology, Singapore General Hospital, National Neuroscience Institute, Singapore. gnrdsd@sgh.com.sg.
Deidre A
DA
De Silva
Leonid
L
Churilov
Jean-Marc
JM
Olivot
Soren
S
Christensen
Maarten G
MG
Lansberg
Michael
M
Mlynash
Bruce C V
BC
Campbell
Patricia
P
Desmond
Matus
M
Straka
Roland
R
Bammer
Gregory W
GW
Albers
Stephen M
SM
Davis
Geoffrey A
GA
Donnan
D000368:Aged; D000369:Aged, 80 and over; D001157:Arterial Occlusive Diseases / Q000188:drug therapy* / Q000473:pathology; D015897:Comorbidity; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology; D015912:Thrombolytic Therapy / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator