- Design
- Systematic review and random-effects meta-analysis of randomised controlled trials
- Population
- 14 trials, 4,944 patients; mean age 69.8, median NIHSS 9; 2,492 received extended-window thrombolysis at 4.5–24 hours
- Primary outcome
- Excellent functional outcome (mRS 0–1) at 3 months and symptomatic intracranial haemorrhage
- Effect
- mRS 0–1 OR 1.43 (95% CI 1.25–1.63); symptomatic intracranial haemorrhage OR 2.51 (1.47–4.28); mortality OR 1.21 (0.95–1.53)
Fourteen randomised trials and 4,944 patients were pooled to test intravenous thrombolysis given between 4.5 and 24 hours after onset or last known well, in patients selected by imaging, against standard care. Mean age was 69.8 years, median NIHSS was 9, and 12.3% had preplanned endovascular thrombectomy.
Extended-window thrombolysis raised the odds of an excellent outcome at three months, modified Rankin Scale 0–1 (odds ratio 1.43, 95% CI 1.25–1.63), of a good outcome, mRS 0–2 (1.25, 1.11–1.40), and of recanalisation (3.28, 2.09–5.16). Mortality did not differ (1.21, 0.95–1.53). Symptomatic intracranial haemorrhage rose sharply: odds ratio 2.51 (1.47–4.28). Excluding patients who also had thrombectomy did not change the picture.
The agent comparison is suggestive and not settled. Tenecteplase carried a lower odds ratio for symptomatic haemorrhage (1.96, 1.06–3.64) than alteplase (5.29, 1.80–15.57), but the subgroup difference was not significant (P = 0.11) and no trial compared them head to head in this window. The practical position is that imaging-selected late thrombolysis is a real option with a real bleeding cost — and that it requires the perfusion or mismatch imaging the trials used, not a plain CT and a willingness to extend the clock.
- Do not extend the window without the imaging selection the trials used — perfusion or diffusion-FLAIR mismatch is the entry criterion, not the time itself.
- Consent explicitly for the raised symptomatic haemorrhage risk; it is the part a patient and family need in plain numbers.
- Where thrombectomy is available and the patient has a large-vessel occlusion, that pathway is not displaced by this.
- Tenecteplase may bleed less in this window, but no trial has compared the two agents here directly — do not present it as established.
- In Indian centres without round-the-clock perfusion imaging, the honest answer is that this strategy is not currently deliverable, and pretending otherwise risks thrombolysing unselected late presenters.
Why it matters
The 4.5-hour rule has defined stroke thrombolysis for two decades, and imaging selection rather than the clock is now what decides eligibility.
Don't overread it
The tenecteplase advantage is a non-significant subgroup comparison, not a demonstrated difference between agents.
The statistics, in plain English
The two headline numbers pull in opposite directions and both are real: an odds ratio of 1.43 for excellent outcome and 2.51 for symptomatic intracranial haemorrhage. Because excellent outcomes are common and symptomatic haemorrhage is rare, a large relative increase in bleeding can still sit alongside a net benefit — which is what the unchanged mortality (1.21, 0.95–1.53) suggests. The alteplase and tenecteplase intervals overlap heavily, and P = 0.11 for the subgroup difference means this analysis cannot tell them apart.
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