Tenecteplase versus alteplase in elderly stroke: a post hoc analysis of the AcT trial

BACKGROUND: Stroke rates rise steeply with age but data on tenecteplase in patients ≥80 years remain limited. This post-hoc analysis of the AcT trial compared tenecteplase with alteplase in this population. METHODS: The analysis included all Alteplase Compared to Tenecteplase in Patients with Acute Ischemic Stroke (AcT) trial participants aged 80 years or older who were randomised to tenecteplase (0.25 mg/kg single bolus) or alteplase (0.9 mg/kg over 60 min). The primary outcome was excellent functional recovery (Modified Rankin Scale (mRS) score: 0-1 at 90-120 days). Secondary outcomes included mRS score 0-2, ordinal mRS shift and safety endpoints including symptomatic intracerebral haemorrhage (sICH) and mortality. Generalised mixed-effects models adjusted for baseline covariates with site as a random effect. Exploratory analyses examined the treatment-by-time interaction using continuous onset-to-needle time (OTN), outcomes by endovascular thrombectomy (EVT) status and outcomes in patients aged≥90 years. RESULTS: Among 543 patients aged ≥80 years (286 tenecteplase, 257 alteplase; mean age 86.9 years), baseline characteristics were balanced. Rates for mRS 0-1 (22.7% vs 23.1%; adjusted RR 0.94, 95% CI 0.74 to 1.19; p=0.63) and mRS 0-2 (37.4% vs 35.5%; adjusted RR 1.02, 95% CI 0.85 to 1.13) were similar, with no significant shift across the ordinal mRS distribution. Mortality (24.5% vs 27.3%) and sICH (3.5% both groups) did not differ. Longer OTN was associated with lower functional independence (adjusted OR per 30 min delay 0.89, 95% CI 0.77 to 1.03), although this did not reach statistical significance. Outcomes were consistent across EVT (n=149) and non-EVT (n=394) subgroups and in patients aged ≥90 years (n=160). CONCLUSIONS: Tenecteplase and alteplase showed comparable efficacy and safety in patients ≥80 years supporting tenecteplase as a reasonable alternative to alteplase in elderly stroke patients.