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May - 2018

   

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Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke

BCV Campbell, ML Churilov, N Yassi et al for the EXTEDN-IA TNK Invetigators N Eng J Med, 2018, 378:1573-82

Comment

Is alteplase or tenecteplase superior as the thrombolytic agent prior to thrombectomy in eligible patients with acute ischemic stroke?

Several trials have reported low incidence of large vessel repercussion with alteplase, and tenecteplase is a genetically modified variant of alteplase with grater fibrin specificity and loner half life permitting bolus administration rather than 1 hour infusion. 

The Tenecteplase versus Alteplase before Endovascular Therapy for Ischemic Stroke (EXTEND-IA TNK) trial;

  • randomised 202 patients with ischemic stroke and occlusion of the internal carotid, basilar, or middle cerebral artery and eligible to undergo thrombectomy to;
  • tenecteplase (0.25 mg per kilogram; max dose, 25 mg) or;
  • alteplase (0.9 mg per kilogram; max dose, 90 mg) 
  • within 4.5 hours after symptom onset. 
  • 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. 
    • 22% tenecteplase vs 10% alteplase (AD, 12%; 95% CI 2 to 21; RR, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority
  • Tenecteplase resulted better 90-day functional outcome (median modified Rankin scale score, 2 vs. 3; OR, 1.7; 95% CI, 1.0 to 2.8; P=0.04).  (scale 0 [no neurologic deficit] to 6 [death]). It is important to not that recovery to independent function did not differ significantly (64% T vs 51% A, p=0.06)
  • Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group.

The authors note this trial applies to patients with ischaemic stroke and large vessel occlusion who are eligible for thrombectomy, a group that accounts for 13% of all patients with ischaemic stroke. A phase 3 trial of tenecteplase vs alteplase in patients in whom endovascular thrombectomy, with primary outcome of functional recovery, is not planned is underway in Australia.

 

Abstract

BACKGROUND

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.

METHODS

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.

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 (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.

CONCLUSIONS

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.

May


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