SOURCE: Campbell BCV, Mitchell PJ, Churilov L, et al; for the EXTEND-IA TNK Investigators. Tenecteplase versus alteplase before thrombectomy for ischemic stroke. N Engl J Med 2018;378:1573-1582.

Intravenous thrombolysis with alteplase is the sole approved treatment for eligible patients with acute ischemic stroke. It also is used to treat patients before endovascular thrombectomy, although this recommendation remains controversial. Alteplase is given as an infusion over one hour after a bolus injection and has been associated with a low incidence of reperfusion for large vessel occlusion before thrombectomy. Tenecteplase is a genetically modified variant of alteplase with greater fibrin specificity and a longer half-life that permits bolus administration, and in trials involving acute myocardial infarction, it had a lower incidence of systemic hemorrhage than alteplase. Tenecteplase is easier to administer and costa less than alteplase.

Campbell et al enrolled 202 patients at 13 centers in Australia and New Zealand who were eligible if they could undergo intravenous thrombolysis within 4.5 hours after onset of ischemic stroke and had a large vessel occlusion on CT angiography of the internal carotid artery, the first or second segments of the middle cerebral artery, or the basilar artery, and treatment could begin to retrieve the intra-arterial clots within six hours after stroke onset. There was no upper age limit and no restriction on clinical severity. Equal numbers of patients were assigned randomly to receive tenecteplase or alteplase. The primary outcome, reperfusion of > 50% of the involved territory or an absence of retrievable thrombus, occurred in 22% of patients treated with tenecteplase vs. 10% of those treated with alteplase (incidence difference = 12 points; P = 0.002 for noninferiority; P = 0.03 for superiority). Tenecteplase treatment resulted in a better 90-day functional outcome than alteplase, and symptomatic intracerebral hemorrhage occurred in 1% of patients in each group.

Treatment with tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase if administered to patients with ischemic stroke within 4.5 hours of symptom onset.