Thrombolysis prior to endovascular thrombectomy increases 90-day functional independence (RR 1.12) in large-vessel strokeCombining medications and procedures may improve outcomes for stroke patients

This meta-analysis evaluated the clinical impact of thrombolysis (IVT) administered prior to endovascular thrombectomy (EVT) in patients presenting with large-vessel acute ischemic stroke. The analysis included a substantial sample size of 10538 patients, providing a broad overview of outcomes for those receiving bridging therapy compared to those receiving EVT alone.

The primary outcome measured was 90-day functional independence, defined as a modified Rankin Scale (mRS) score of 0-2. The meta-analysis reported that patients receiving thrombolysis prior to EVT achieved higher rates of 90-day functional independence with an RR of 1.12 (95% CI 1.05-1.20). This suggests a statistically significant improvement in functional outcomes for the bridging therapy group.

Secondary outcomes included reperfusion success, mortality, and complications. Successful reperfusion, defined as mTICI score greater than or equal to 2b, was higher in the thrombolysis prior to EVT group (RR 1.04, 95% CI 1.01-1.06). Furthermore, the study reported lower 90-day mortality for patients receiving thrombolysis before EVT (RR 0.80, 95% CI 0.69-0.91). However, these benefits were accompanied by a significant safety trade-off: there was a significantly increased risk of symptomatic intracranial hemorrhage (sICH) in the group receiving thrombolysis prior to EVT (RR 1.35, 95% CI 1.03-1.65).

The results indicate that while bridging therapy with thrombolysis may improve functional independence and reperfusion rates compared to EVT alone, it carries a higher risk of symptomatic intracranial hemorrhage. The study notes that the benefit of IVT prior to EVT is offset by this increased risk of sICH. This finding suggests that the clinical utility of bridging therapy must be weighed against the specific bleeding risks of the individual patient.

Methodologically, the analysis noted that randomized controlled trials (RCTs) and low-dose alteplase did not show significant results in certain contexts. The evidence for the observed benefits is primarily derived from observational data; therefore, a definitive causal link between thrombolysis prior to EVT and improved outcomes is not established by randomized evidence alone. The certainty of these findings was evaluated using the GRADE framework.

Clinically, these results suggest that there is no universal approach to bridging therapy. Instead, practitioners should make individualized treatment decisions based on factors such as workflow efficiency, stroke severity, and specific bleeding risks. For patients with high risk of hemorrhage, the increased sICH rate (RR 1.35) may be a significant deterrent despite potential gains in functional independence.

Several questions remain regarding the optimal timing for thrombolysis and the specific thresholds for selecting patients who would benefit most from bridging therapy while minimizing sICH risks. Additionally, further research into different agents or lower doses of alteplase might clarify why certain trial designs failed to show significant results compared to these observational findings.