BACKGROUND: The safety and efficacy of treatment with intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion remain uncertain.
METHODS: In this open-label trial conducted in China, we randomly assigned patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset and were eligible for thrombolysis to receive either intravenous tenecteplase followed by endovascular thrombectomy or endovascular thrombectomy alone. The primary outcome was functional independence (a score of 0 to 2 on the modified Rankin scale; range, 0 to 6, with higher scores indicating more severe disability) at 90 days. Secondary outcomes included successful reperfusion before and after thrombectomy. Safety outcomes included symptomatic intracranial hemorrhage within 48 hours and death within 90 days.
RESULTS: A total of 278 patients were randomly assigned to the tenecteplase-thrombectomy group and 272 to the thrombectomy-alone group. Functional independence at 90 days was observed in 147 patients (52.9%) in the tenecteplase-thrombectomy group and in 120 patients (44.1%) in the thrombectomy-alone group (unadjusted risk ratio, 1.20; 95% confidence interval, 1.01 to 1.43; P = 0.04). A total of 6.1% of the patients in the tenecteplase-thrombectomy group and 1.1% of those in the thrombectomy-alone group had successful reperfusion before thrombectomy, and 91.4% and 94.1%, respectively, had successful reperfusion after thrombectomy. Symptomatic intracranial hemorrhage within 48 hours occurred in 8.5% of the patients in the tenecteplase-thrombectomy group and in 6.7% of those in the thrombectomy-alone group; mortality at 90 days was 22.3% and 19.9%, respectively.
CONCLUSIONS: Among patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset, the percentage of patients with functional independence at 90 days was higher with intravenous tenecteplase plus endovascular thrombectomy than with endovascular thrombectomy alone. (Funded by the Chongqing Science and Health Joint Medical Research Project and others; BRIDGE-TNK ClinicalTrials.gov number, NCT04733742.).
| Discipline Area | Score |
|---|---|
| Emergency Medicine |  |
| Neurology | |
| Internal Medicine | Coming Soon... |
These results expand on the time frame in which tenecteplase may be used to bridge to thrombectomy in patients presenting with acute large-vessel occlusion. This may be particularly relevant to practitioners in rural and regional environments where transport time may be of more relevance. I will use this evidence in discussion of therapy and disposition with stroke neurology.
This adds strength to a recent ACEP Clinical Policy Level B recommendation for TNK as thrombolytic with mechanical thrombectomy within 4.5 hours of symptoms (https://www.acep.org/patient-care/clinical-policies/thrombolytics-for-the-management-of-acute-ischemic-stroke).
In this RCT, patients receiving tenecteplase had better functional outcomes compared with those who did not when going for thrombectomy. These data are consistent with a recent meta-analysis. Although another recent study showed similar results, the proposed variable of time >140 min was favored in this trial but not the other. This trial also does not include those that were transferred for thrombectomy, so that cannot be definitively answered. While more trials are currently ongoing, it's clear that thrombolysis prior to thrombectomy should still be the standard of care.
In my experience, thrombolysis is almost routinely initiated (if indicated) prior to a potential thrombectomy. The thrombolysis begins early while the Neurologist evaluates the indication for potential mechanical endovascular intervention based on the CT images. These are certainly reassuring results regarding a practice that is already commonly adopted, at least where I practice (Italy).
This trial confirms that intravenous tenecteplase followed by mechanical thrombectomy is more effective than thrombectomy alone; however, only Chinese patients were included, so low external validity.
Although this study has drawbacks (single study, open label, etc), it is the first major randomized trial to suggest tenecteplase prior to thrombectomy might show efficacy. There is controversy about whether this is due to tenecteplase itself or the very rapid treatment time. Regardless, this is relevant for everyday stroke practice given the wide availability of tenecteplase and various approaches to combined therapy.
Adding TNK to thrombectomy may theoretically increase risk for hemorrhage and previous trials have been unclear as to offsetting benefits. This study is helpful in demonstrating the benefit of adding TNK to functional recovery with no significant safety hazard identified. Decision-making in hyperacute treatment is now easier: administer TNK and proceed to thrombectomy.