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Original paper
2018NEJMNeurology

EXTEND-IA TNK

Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke

RCTAcute ischemic stroke

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Overview

Before thrombectomy for large-vessel occlusion, tenecteplase 0.25 mg/kg achieved more reperfusion and better 90-day function than alteplase.

Clinical takeaway

In thrombectomy-eligible large-vessel occlusion, tenecteplase produced more early reperfusion and better 90-day function than alteplase.

Key result

Substantial reperfusion at first angiography occurred in 22% with tenecteplase vs 10% with alteplase (incidence ratio 2.2; 95% CI 1.1-4.4; p=0.03 for superiority).

Practice impact

Prefer bolus tenecteplase 0.25 mg/kg over alteplase when giving lytic therapy before thrombectomy.

Evidence

Study design

Randomized comparison of tenecteplase versus alteplase before thrombectomy, tested first for noninferiority then superiority.

Enrollment

202

Follow-up

Modified Rankin scale assessed at 90 days.

Geography

Not listed

Clinical question

Does tenecteplase before thrombectomy produce more reperfusion than alteplase in large-vessel occlusion stroke treated within 4.5 hours?

Population

  • Patients with ischemic stroke from occlusion of the internal carotid, basilar, or middle cerebral artery who were eligible for thrombectomy and could be treated within 4.5 hours after symptom onset.

Intervention

Tenecteplase 0.25 mg per kilogram (maximum 25 mg).

Comparator

Alteplase 0.9 mg per kilogram (maximum 90 mg).

Primary outcome

Reperfusion of greater than 50% of the involved ischemic territory or absence of retrievable thrombus at initial angiographic assessment.

Tenecteplase before thrombectomy was noninferior and then superior to alteplase for substantial early reperfusion.

Incidence ratio / 2.2 / 95% CI 1.1-4.4 / p=0.03

Key results

  • The primary reperfusion outcome occurred in 22% with tenecteplase vs 10% with alteplase (incidence difference 12 percentage points; 95% CI 2-21; incidence ratio 2.2; 95% CI 1.1-4.4; p=0.002 for noninferiority; p=0.03 for superiority).
  • Median 90-day modified Rankin scale score was 2 with tenecteplase vs 3 with alteplase (common OR 1.7; 95% CI 1.0-2.8; p=0.04).

Harms

  • Symptomatic intracerebral hemorrhage occurred in 1% of patients in each group.

Clinical Use

Practice impact

  • Prefer bolus tenecteplase 0.25 mg/kg over alteplase when giving lytic therapy before thrombectomy.

Applicability

  • Most applicable to thrombectomy-eligible internal carotid, middle cerebral, or basilar occlusion treated with a lytic within 4.5 hours.

Limitations

  • This is a large-vessel-occlusion, thrombectomy-bound population, not all ischemic stroke.
  • The primary endpoint was angiographic reperfusion, not disability, although 90-day function also improved.
  • The trial enrolled 202 patients, all bound for thrombectomy.

Common misinterpretations

  • Do not generalize this reperfusion advantage to patients who are not going to thrombectomy.
  • Alteplase was not unsafe here; symptomatic hemorrhage was 1% in both groups.

Related evidence

AcT - Similar QuestionMR CLEAN - Earlier TrialECASS III - Context

Citation

Campbell BCV, Mitchell PJ, Churilov L, et al. Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke. N Engl J Med. 2018;378(17):1573-1582. doi:10.1056/NEJMoa1716405

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.