Low-Dose Tenecteplase Prior to EVT Improves 90-Day Post-Stroke Outcomes in Elders

Vignan Yogendrakumar, MD, MSc

Pooled analyses from the EXTEND-IA TNK randomized controlled trial (NCT02388061) showed that treatment with tenecteplase 0.25 mg/kg before endovascular therapy improved 90-day functional outcome and mortality better than 0.40 mg/kg doses in elders aged at least 80 years with large vessel occlusion (LVO) stroke.¹

In this analysis, investigators aimed to understand whether there are differences in the safety and efficacy of tenecteplase dosing in older patients who present with ischemic stroke within 4.5 hours of symptom onset. Led by Vignan Yogendrakumar, MD, MSc, stroke fellow and PhD candidate, University of Melbourne, patients were first randomized to open-label tenecteplase 0.25 mg/kg or alteplase 0.90 mg/kg prior to initiation of endovascular therapy. In part 2, patients were randomized to open-label tenecteplase 0.25 mg/kg or 0.40 mg/kg.

At the time of randomization and treatment, 137 (27%) of the 502 originally enrolled patients were older than 80 years of age. After adjusting for relevant covariates, tenecteplase 0.25 mg/kg was associated with improved modified Rankin Scale (mRS) scores at 90 days compared with tenecteplase 0.40 mg/kg (adjusted common OR, 2.70 [95% CI, 1.23-5.94]) and alteplase (adjusted common OR, 2.28 [95% CI, 1.03-5.05]). Notably, there was no difference between the alteplase and tenecteplase 0.40 mg/kg groups.

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Overall, only one-third of those older than 80 years of age achieved disability freedom or were functionally independent at 90 days, with the highest proportion of patients observed in the tenecteplase 0.25-mg/kg group. This difference was found to be statistically significant when compared with patients treated with alteplase (freedom from disability: 42% vs 17% [adjusted OR, 8.54 (95% CI, 1.83-39.79)]; functional independence: 43% vs 32% [adjusted OR, 4.11 (95% CI, 1.06-15.90)]).

Mortality, occurring in 30% of the cohort, was highest in those treated with Tenecteplase 0.40 mg/kg (41%) and alteplase (34%). Conversely, the 0.25 mg/kg dose group were associated with reduced mortality (adjusted OR, 0.34 [95% CI, 0.13-0.91]) versus the 0.40 mg/kg group.

"Based on our sensitivity analysis, the increased mortality seen with tenecteplase 0.40 mg/kg dosing was largely explained by the higher rates of hemorrhage and is in keeping with previous cardiovascular literature that suggested an increased risk of bleeding in patients with 0.50 mg/kg doses of tenecteplase,” Yogendrakumar et al wrote. "The rates of symptomatic hemorrhage in our analysis are also in keeping with an analysis of older stroke patients from the NOR-TEST trial."

In total, 4 older patients with tenecteplase 0.40 mg/kg experienced symptomatic intracranial hemorrhage, compared with 1 patient treated with alteplase, and zero patients treated with tenecteplase 0.25 mg/kg. All patients aged at least 80 years who had a symptomatic intracranial hemorrhage and 5 out of 7 individuals who had a parenchymal hemorrhage died within the follow-up period.

Between the 3 treatment groups, rates of successful reperfusion at initial angiographic assessment did not significantly differ (tenecteplase 0.25 mg/kg: 27%; tenecteplase 0.40 mg/kg: 29%; alteplase 0.90 mg/kg, 10%). Additionally, there was no significant difference in follow-up core volumes between the different treatment groups.

For the remaining cohort of individuals aged 80 years or younger, no differences were observed in 90-day mRS between the 3 treatment groups. Rates of freedom from disability and functional independence were higher in this cohort, ranging from 53%-69%, compared with those who were older than 80 years of age. Mortality and symptomatic intracranial hemorrhage were also less frequent than the older cohort and were comparable amongst all 3 treatment groups.

REFERENCE
1. Yogendrakumar V, Churilov L, Mitchell PJ, et al. Safety and efficacy of tenecteplase in older patients with large vessel occlusion: a pooled analysis of the EXTEND-IA TNK trials. Neurology. Published online January 11, 2022. doi:10.1212/WNL.0000000000013302