When do you offer TNK for ischemic stroke patients with a large vessel occlusion presenting outside the 4.5-hour window?

I agree with Dr. @Dr. First Last. Generally, I do not treat with TNK if EVT is available, but I do treat if no EVT is available, assuming favorable imaging as per the TRACE-III trial. However, as with all decisions, there are nuances. Since the benefit and risk ratio of TNK was only slightly favorable in TRACE-III, I would not treat if the patient had relative cautions suggesting higher bleeding risk (e.g., on dual antiplatelets) or had exclusions from the trial (e.g., pre-existing disability among others).

On the other hand, in the TIMELESS trial, the average time from TNK to EVT was only 16 minutes, hardly enough time for TNK to have much effect. Even so, more patients in the TNK group no longer had a visible clot when the EVT procedure wa...

If you had readily available access to EVT (as did patients in TIMELESS), then there does not seem to be an added benefit of giving TNK to these patients.

Moreover, the IRIS meta-analysis showed no added benefit of alteplase before EVT in patients presenting directly to EVT centers if treatment was beyond 2.5 hours (so the benefit is less likely if even beyond, 4.5 hours).

Reference: Kaesmacher et al., PMID 38324409

The CLEAR study, in which patients had access to EVT, showed in the world (i.e., outside RCTs), no added benefit of IVT (mostly with alteplase) added to EVT, in the >4.5 hour window.

Reference: Demeestere et al., PMID 38748598

If you had no EVT access, it may be reasonable to administer based on the imaging parameters used in the TRA...