Intravenous thrombolysis before endovascular thrombectomy (EVT) in stroke patients has potential benefits for improving reperfusion but also carries a risk of increased intracranial haemorrhage. Since 2018, six randomised trials have found no significant difference in outcomes between combining thrombolysis (mainly with alteplase) and EVT versus EVT alone. Tenecteplase, a newer thrombolytic agent with pharmacokinetic advantages over alteplase, has shown promise in some studies but lacks robust evidence, particularly in direct comparison with EVT alone.
To address this gap, the Randomized Trial of Thrombectomy with versus without Recombinant Human Tenecteplase (TNK) Tissue Plasminogen Activator in Stroke (BRIDGETNK) trial was conducted to evaluate whether intravenous tenecteplase before EVT improves functional independence at 90 days without increasing haemorrhagic risk.
In this trial, patients with acute ischaemic stroke from large-vessel occlusion presenting within 4.5 hours and eligible for thrombolysis were randomly assigned to receive either intravenous tenecteplase followed by EVT or EVT alone. The primary outcome was functional independence at 90 days. Secondary outcomes included successful reperfusion before and after EVT. Safety outcomes assessed were symptomatic intracranial haemorrhage within 48 hours and death within 90 days.
278 patients received tenecteplase plus thrombectomy, and 272 received thrombectomy alone. At 90 days, functional independence was achieved in 52.9% of the tenecteplase group versus 44.1% of the thrombectomy-alone group. Successful reperfusion before thrombectomy occurred in 6.1% of the tenecteplase group and 1.1% of the thrombectomy-alone group, while post-thrombectomy reperfusion rates were 91.4% and 94.1%, respectively. Symptomatic intracranial haemorrhage within 48 hours occurred in 8.5% (tenecteplase group) vs. 6.7% (control), and 90-day mortality was 22.3% vs. 19.9%, respectively.
The BRIDGE-TNK trial found that in patients with acute ischaemic stroke due to large-vessel occlusion who presented within 4.5 hours and were eligible for thrombolysis, treatment with intravenous tenecteplase followed by EVT led to a higher rate of functional independence at 90 days compared to EVT alone. However, secondary outcomes showed no significant differences between the groups, and the benefits observed were modest.
Reperfusion before thrombectomy occurred more often in the tenecteplase group (6.1% vs. 1.1%), and the time from arterial puncture to reperfusion was shorter by 9 minutes, potentially contributing to better outcomes. Safety outcomes, including symptomatic intracranial haemorrhage and overall haemorrhage rates on imaging, were similar between groups.
While the findings support benefit of tenecteplase plus EVT within 4.5 hours, they do not establish superiority across all outcomes. Further trials and meta-analyses (e.g., combining BRIDGE-TNK with RESILIENT DIRECT-TNK) are needed to clarify tenecteplase’s role, especially in extended time windows or transfer settings.
Source: NEJM
Image Credit: iStock
References:
Qui Z, L F, Sang H et al. (2025) Intravenous Tenecteplase before Thrombectomy in Stroke. NEJM.
