Tenecteplase bests alteplase for distal occlusions

In the secondary analysis of the TASTE trial, tenecteplase is associated with better clinical outcomes than alteplase in individuals with distal vessel occlusions (DVOs).

The efficacy of tenecteplase has been previously assessed in individuals presenting with large or medium VOs detectable on imaging, noted Dr Vignan Yogendrakumar from The Ottawa Hospital Research Institute, Ontario, Canada, during his presentation at ISC 2026.

“However, its efficacy for more distal occlusions, such as those in the distal branches of the middle cerebral artery (MCA) or in the anterior cerebral artery (ACA) or posterior cerebral artery (PCA) territories, remains largely underinvestigated,” he said.

Hence, Yogendrakumar and colleagues sought to evaluate the potential of tenecteplase vs alteplase across a range of VO sites, with particular focus on distal MCA, ACA, and PCA occlusions. [ISC 2026, abstract A005]

The team conducted a secondary analysis of the phase III TASTE trial, which evaluated patients with acute ischaemic stroke presenting within 4.5 hours of symptom onset. A total of 680 participants were randomized 1:1 to tenecteplase or alteplase. This secondary analysis comprised 492 patients (median age 73 years, 62 percent men, median NIHSS* 7).

Over a third (35 percent) of participants had VOs at the third segment of the MCA and beyond distally (distal MCA). Other VO sites were as follows: proximal second segment (M2) of the MCA (20 percent), distal M2 of the MCA (19 percent), PCA (18.5 percent), and ACA (7 percent).

At 90 days, the percentage of participants achieving the primary outcome of modified Rankin Scale (mRS) 0–1 was higher with tenecteplase than with alteplase in the subgroup of participants with distal MCA (77 percent vs 63 percent; adjusted risk ratio [aRR], 1.23). A similar trend was seen in the distal M2 (65 percent vs 58 percent; aRR, 1.14) and ACA subgroups (57 percent vs 38 percent; aRR, 1.46).

The pattern favouring tenecteplase over alteplase was consistently observed for the secondary outcome of mRS 0–2 at 90 days in the distal MCA (88 percent vs 81 percent; aRR, 1.09), distal M2 (80 percent vs 71 percent; aRR, 1.15), and ACA subgroups (81 percent vs 61 percent; aRR, 1.26).

“When looking at mRS 5–6, we did not see any major differences in severe disability or mortality, nor did we see any major differences in symptomatic intracranial haemorrhage (SICH) between treatment groups and across VO sites. There were no SICH events in the ACA or PCA subgroups,” said Yogendrakumar.

The 90-day mRS 5–6 with tenecteplase and alteplase were 5 percent and 3 percent in the distal MCA subgroup (aRR, 1.51), 10 percent and 8 percent in the proximal M2 subgroup (aRR, 1.19), and 8 percent and 4 percent in the PCA subgroup (aRR, 3.02), after adjusting for age, baseline NIHSS, and premorbid mRS on Firth’s logistic regression.

There were very low incidences of SICH, with only five occurring in the tenecteplase group (n=1, 2, and 2 in the proximal M2, distal M2, and distal MCA subgroups) and three in the alteplase group (one in each of the aforementioned subgroups). According to Yogendrakumar, these reinforce the favourable safety profile of tenecteplase.

Moreover, there were no differences in the aRRs between treatment groups across the PCA and ACA subgroups.

However, Yogendrakumar acknowledged that the results are hypothesis-generating, as this was a secondary analysis. The study sample size was also limited for evaluating ACA occlusions. Moreover, no adjustments were made for multiple comparisons.

“[Nonetheless, these] findings reinforce the role of tenecteplase as a reliable agent within standard acute stroke workflows,” said Yogendrakumar.