EXTEND-IA TNK: Tenecteplase is superior to alteplase as neoadjuvant treatment for mechanical thrombectomy

1. When treated with tenecteplase, stroke patients eligible for mechanical thrombectomy had higher rates of reperfusion and superior clinical outcomes at 90 days relative to patients treated with alteplase.

2. There was no evidence that rates of intracerebral hemorrhage were different between the tenecteplase and alteplase groups.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Recombinant tissue plasminogen activator, given as alteplase, has for many years been a cornerstone of acute stroke treatment. These patients often receive alteplase, a recombinant tissue plasminogen activator (tPA), prior to thrombectomy. Tenecteplase is another recombinant tPA that has greater specificity for fibrin and a longer half-life. It is unclear which recombinant tPA is superior as bridging therapy prior to mechanical thrombectomy.

This randomized controlled trial enrolled patients with large vessel stroke eligible to undergo thrombectomy and randomized them to pretreatment with tenecteplase or alteplase. The primary outcome was a predetermined degree of reperfusion. A key secondary outcome was clinical outcome assessed by the modified Rankin scale. The investigators found that patients receiving tenecteplase had higher rates of the tissue reperfusion and higher modified Rankin scale scores at 90 days.

Strengths of the study include its randomized, multicenter design. The use of a surrogate outcome as the primary outcome in the study is a weakness, as it may not translate to meaningful clinical outcomes. Furthermore, the trial was powered for noninferiority rather than superiority. Overall, these results support consideration for use of tenecteplase rather than alteplase prior to endovascular thrombectomy.

Click to read the study, published in NEJM

Relevant Reading: Tenecteplase versus alteplase for management of acute ischaemic stroke (NOR-TEST): a phase 3, randomised, open-label, blinded endpoint trial

In-Depth [randomized controlled trial]: This was a phase three, multicenter, blinded randomized controlled trial that enrolled 202 patients (n = 101 in alteplase and tenecteplase groups) between 2015 and 2017 to compare outcomes amongst patients treated with either alteplase or tenecteplase prior to mechanical thrombectomy. Key inclusion criteria included onset of symptoms within 4.5 hours and large-vessel occlusion of either the internal carotid, middle cerebral, or basilar artery. There was no restriction by NIH stroke scale score, but patients with preexisting disability per the modified Rankin scale score were excluded. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory, or absence of thrombus during angiography. Secondary outcomes included score at 90 days on the modified Rankin scale, and early improvement in National Institutes of Health Stroke Scale score (NIHSS) at 24 and 72 hours.

The primary outcome occurred in 22% of tenecteplase and 10% of alteplase patients, respectively. The study arm was noninferior (P = 0.002) and superior (P = 0.02) to the comparator group (adjusted odds ratio [aOR], 2.6; 95% confidence interval [CI], 1.1 to 5.9). The median modified Rankin scale score was was 2 in the tenecteplase group, and 3 in the alteplase group (odds ration [OR], 1.7; 95% CI, 1.0 to 2.8; P = 0.04). Evidence of early neurologic improvement (within 24 or 72 hours) did not meet the threshold or statistical significance (P24 = 0.06, P72 = 0.053). One patient in both the tenecteplase and alteplase group had a symptomatic intracerebral hemorrhage.

Image: PD

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