Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.

2018-04-26

Campbell, Bruce C V

Mitchell, Peter J

Churilov, Leonid

Yassi, Nawaf

Kleinig, Timothy J

Dowling, Richard J

Yan, Bernard

Bush, Steven J

Dewey, Helen M

Thijs, Vincent

Scroop, Rebecca

Simpson, Marion A

Brooks, Mark

Asadi, Hamed

Wu, Teddy Y

Shah, Darshan G

Wijeratne, Tissa

Ang, Timothy

Miteff, Ferdinand

Levi, Christopher R

Rodrigues, Edrich

Zhao, Henry

Salvaris, Patrick

Garcia-Esperon, Carlos

Bailey, Peter

Rice, Henry

de Villiers, Laetitia

Brown, Helen

Redmond, Kendal

Leggett, David

Fink, John N

Collecutt, Wayne

Wong, Andrew A

Muller, Claire

Coulthard, Alan

Mitchell, Ken

Clouston, John

Mahady, Kate

Field, Deborah

Ma, Henry

Phan, Thanh G

Chong, Winston

Chandra, Ronil V

Slater, Lee-Anne

Krause, Martin

Harrington, Timothy J

Faulder, Kenneth C

Steinfort, Brendan S

Bladin, Christopher F

Sharma, Gagan

Desmond, Patricia M

Parsons, Mark W

Donnan, Geoffrey A

Davis, Stephen M

Journal Article

0000-0003-3632-9433

0000-0002-6614-8417

10.1056/NEJMoa1716405

Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

link

The New England Journal of Medicine 2018; 378(17): 1573-1582

The New England Journal of Medicine