Tenecteplase improves reperfusion across time in large vessel stroke

Patients with large vessel occlusion have higher rates of thrombolytic-induced reperfusion with tenecteplase compared to alteplase, regardless of the time from administration to reperfusion assessment, Australian research shows.

A Melbourne study’s findings provide further support for the use of tenecteplase as the preferred agent in “drip-and-ship models of stroke care,” according to leading stroke clinicians.

The study comprised 893 patients, pooled from the EXTEND-IA trials and Melbourne Stroke Registry, and treated with thrombolysis within 4.5 hours of symptom onset between 2017 and 2020.

The primary outcome of thrombolytic-induced reperfusion, defined as the absence of retrievable thrombus or >50% reperfusion on repeat imaging assessment, was observed in 21% of tenecteplase patients and 19% of alteplase patients.

However median times from thrombolytic to reperfusion assessment were longer in those who received alteplase compared to tenecteplase (93 v 63 mins).

“Accounting for thrombolytic to assessment time, tenecteplase was associated with higher rates of thrombolytic-induced reperfusion (aIRR 1.50 (95% CI: 1.09-2.07),” the study said.

The study, published in Annals of Neurology [link here], said successful reperfusion, either through early reperfusion with a thrombolytic or following endovascular therapy, was achieved in most patients (86%).

Early reperfusion was associated with improved mRS scores at 90 days (OR 2.1) when compared to post-endovascular therapy reperfusion.

“Patients who achieved early reperfusion with thrombolysis had increased rates of freedom from disability (adjusted OR: 2.46 [95% CI: 1.64-3.68]), functional independence (adjusted OR: 2.85 [95% CI: 1.82-4.46]), and reduced rates of mortality (adjusted OR: 0.43 [95% CI: 0.21-0.87]),” it said.

The study proposed potential mechanisms by which tenecteplase achieved higher rates of thrombolytic-induced reperfusion.

“Given the bolus nature of tenecteplase administration, the higher rates of reperfusion may reflect a faster onset of plasmin-generation and therefore, the lytic effect of tenecteplase may be a ‘frontloaded’ phenomenon.”

“However, the longer half-life of tenecteplase, in combination with an increased resistance to plasminogen activator inhibitor, may also extend the drug’s ability to debulk large clot.”

The investigators, including Professor Geoffrey Donnan, Professor Stephen Davis and Professor Bruce Neal, said the analysis was supportive of tenecteplase use in patients requiring transfer to endovascular capable centers.

“In large vessel occlusion patients with thrombolytic to reperfusion assessment times up to 240 minutes, increased rates of early reperfusion with tenecteplase persisted across the time spectrum,” they concluded.

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