PracticeUpdate Neurology Best of 2018

EDITOR’S PICKS 12

Tenecteplase vs Alteplase Before Thrombectomy for Ischemic Stroke The New England Journal of Medicine

Take-home message • The authors of this study sought to determine whether a bolus dose of tenecteplase increases vascular reperfusion following a stroke, when compared with alteplase. In this study, 202 patients were enrolled, of whom 101 received tenecteplase and 101 received alteplase. The primary outcome, 50% or greater reperfusion of the ischemic area or no retrievable thrombus at initial angiographic assessment, was observed in 22% of patients in the tenecteplase group compared with 10% of the alteplase patients (P = .003). Functional outcomes, as measured by the modified Rankin Scale, were better at 90 days in those given tenecteplase than in those given alteplase (P = .04). Safety measures were similar between groups. • The data indicate that tenecteplase is associated with improved reperfusion and functional outcomes compared with alteplase following ischemic stroke. Dustin Chernick

COMMENT By James C. Grotta MD C urrent guidelines recommend administering intravenous tissue plasminogen activator (tPA) to all eligible patients, even if their stroke is due to an intracranial large-vessel occlusion (LVO). Whether this systemic thrombolysis step is useful in LVO patients who will eventually require endovascular thrombectomy (ET) is a matter of debate because tPA is usually unsuccessful in lysing LVOs. The question addressed in the EXTEND-IA TNK study is whether, in LVO patients eligible for ET, tPA can be replaced by tenecteplase (TNK), which has a longer half-life and so can be administered as an IV bolus (vs tPA, which requires a bolus and 1-hour infusion) and is also more fibrin-specific and so might be a more effective lytic. In 202 LVO patients, those randomized to TNK 0.25 mg/kg had twice the rate of good reperfusion (22%) compared with those administered tPA (10%) on arteriography carried out roughly 1 hour later at the start of the ET procedure. Importantly, and somewhat surprisingly, this translated to a better 90-day clinical outcome, emphasizing that, although ET is the most important intervention in LVO patients, earlier reperfusion can produce even better results. Both treatments were associated with a similar very low risk of bleeding. Previous studies of TNK vs tPA have either shown no difference or slight benefit for TNK, and the best TNK dose is still uncertain. TNK may prove to be an alternative to tPA; further studies of TNK vs tPA in both LVO and non-LVO patients are underway and results are eagerly anticipated. Dr. Grotta is Neurologist at Memorial Hermann Medical Group and Director of Stroke Research at Clinical Institute for Research and Innovation, Memorial Hermann–Texas Medical Center in Houston, Texas.

Abstract BACKGROUND Intravenous infusion of alteplase is used for thrombolysis before endovas- cular 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 vas- cular reperfusion. METHODS We randomly assigned patients with ischemic stroke who had occlusion of the inter- nal 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 kilo- gram; 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 out- comes 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.

RESULTS 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 (inci- dence 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. CONCLUSIONS Tenecteplase before thrombec- tomy 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. Tenecteplase Versus Alteplase Before Thrombectomy for Ischemic Stroke. N Engl J Med 2018 Apr 26;378(17)1573-1582, BCV Camp-

bell, PJ Mitchell, L Churilov, et al. www.practiceupdate.com/c/67270

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