Intra-arterial Thrombolysis Fails to Improve Stroke Outcomes

Intra-arterial thrombolysis with urokinase or tenecteplase after successful endovascular thrombectomy (EVT) did not significantly improve outcomes in patients with acute ischemic stroke, according to two randomized trials in China published in JAMA.

The POST-UK trial evaluated intra-arterial urokinase, whereas the POST-TNK trial assessed intra-arterial tenecteplase. Both trials aimed to determine whether administering thrombolytics after near-complete or complete reperfusion during EVT could enhance functional recovery by improving microvascular reperfusion and reducing residual clot burden.

In the POST-UK trial, which enrolled 535 patients (median age, 69 years), those who received intra-arterial urokinase did not have significantly higher rates of survival without disability at 90 days than control individuals who did not receive urokinase (45% vs 40%; adjusted risk ratio [RR], 1.13; P = .19). Similarly, the POST-TNK trial, which included 540 patients, found no significant benefit with intra-arterial tenecteplase (49% vs 41% survival rate in the tenecteplase group vs control group; RR, 1.15; P = .11).

EVT is the standard of care for patients with large vessel occlusion stroke, but many patients continue to experience disability despite successful reperfusion. Previous studies suggested that residual thrombi in distal arteries and microcirculation may limit full neurological recovery. The findings of the trials indicate that adjunctive intra-arterial thrombolysis does not significantly enhance functional outcomes.

Although the primary efficacy outcome in this trial did not show a statistically significant result, “the confidence intervals do not exclude a clinically meaningful benefit of therapy,” the researchers wrote.

Additionally, rates of mortality, symptomatic intracranial hemorrhage, and systemic bleeding were similar between the thrombolysis and control groups in both trials.

“The evidence for an effect of intra-arterial thrombolytics is not yet sufficient to warrant its implementation in clinical practice,” the authors of an accompanying editorial wrote.

Despite a promising mechanistic rationale, neither urokinase nor tenecteplase showed a statistically significant benefit as adjunctive therapy after EVT. Future research may focus on identifying subgroups of patients with stroke who could benefit from additional pharmacologic reperfusion strategies or alternative approaches to enhance microcirculatory flow.