Tenecteplase shows worse functional outcomes in older patients with minor ischemic stroke compared to standard care.

This study represents a post hoc analysis of a randomized controlled trial involving 884 patients with minor ischemic stroke. The population included individuals presenting within 12 hours of symptom onset who had either symptomatic intracranial occlusion or a focal perfusion lesion. The setting of the trial was not reported in the available data. The intervention consisted of intravenous thrombolysis with tenecteplase, compared against nonthrombolytic standard of care. The primary outcome was a responder analysis of the 90-day modified Rankin Scale (mRS), defined as an mRS score of 0-1 for patients with premorbid mRS of 0-1, or an mRS of 0-2 for those with premorbid mRS of 2. Secondary outcomes included neurologic recovery measured by the NIH Stroke Scale (NIHSS) at 5 days or discharge, vessel recanalization rates, Lawton Instrumental Activities of Daily Living Scale scores, and EuroQol-5 Dimension (EQ-5D) quality of life measures. Follow-up for the primary outcome occurred at 90 days.

Analysis of the primary outcome revealed a significant divergence based on age. Among patients older than 80 years, functional outcomes were worse with tenecteplase compared to control. The adjusted risk ratio (aRR) for being a responder was 0.83 (95% CI 0.72-0.97), with 49 patients (46.2%) achieving responder status in the tenecteplase group versus 61 patients (59.8%) in the control group. In contrast, no significant difference in functional recovery was observed among patients aged 80 years or younger. For this younger cohort, the aRR was 1.01 (95% CI 0.98-1.03), with 249 patients (76.4%) in the tenecteplase group and 260 patients (74.7%) in the control group achieving the primary outcome.

Regarding vessel recanalization, patients receiving tenecteplase were more likely to achieve recanalization in both age groups. The aRR for patients ≤80 years was 2.06 (95% CI 1.60-2.65), while for patients >80 years, the aRR was 2.77 (95% CI 2.21-3.47). Absolute numbers for recanalization were not reported. Similarly, the likelihood of achieving an NIHSS score of 0 at 5 days or discharge was higher with tenecteplase in both groups. The aRR for patients ≤80 years was 1.14 (95% CI 1.04-1.26), and for patients >80 years, it was 1.21 (95% CI 1.10-1.33). Data for these secondary outcomes were not reported in absolute numbers.

Safety findings were particularly concerning for the older population. Serious adverse events (SAEs) were more frequent with tenecteplase among patients older than 80 years, with a risk ratio of 2.29 (95% CI 1.27-4.13). Specifically, extra/intracranial hemorrhage occurred more frequently in this group, with 5 cases (4.7%) in the tenecteplase arm versus 0 cases in the control arm (p = 0.026). The study noted that SAEs were more frequent with tenecteplase in older patients, particularly involving hemorrhages and stroke progression or recurrence. Detailed adverse event rates beyond hemorrhage and SAEs were not reported, nor were discontinuation rates or specific tolerability profiles.

The study is classified as Class III evidence due to its nature as a post hoc analysis. A key methodological limitation is that this analysis was not a primary endpoint of the original trial, which may introduce bias. Additionally, the lack of reported funding or conflicts of interest limits the ability to assess potential external influences. The evidence is observational in nature regarding the subgroup analysis, meaning associations should not be interpreted as causation. Furthermore, surrogate markers like recanalization did not translate to improved functional outcomes in the elderly, highlighting the complexity of thrombolysis efficacy in this demographic.

Clinically, these results do not support the use of thrombolysis for minor strokes in patients over 80 years, given the increased risk of hemorrhage and worse functional outcomes without clear benefit in the primary responder analysis. Questions remain regarding the optimal management of minor stroke in the elderly, as the potential for recanalization does not appear to outweigh the safety risks in this specific age group. Further research is needed to determine if alternative interventions or stricter selection criteria could improve the risk-benefit profile for older patients.