A stroke in the last three months should not, by itself, exclude thrombolysis

Design

systematic review and individual-patient-data meta-analysis of published reports

Population

63 patients (44 with individual data) receiving repeated intravenous thrombolysis within 90 days of a previously thrombolysed ischaemic stroke; median interval 7.5 days

Primary outcome

functional outcome and symptomatic intracranial haemorrhage after repeat thrombolysis

Effect

66.7% favourable outcome; pooled OR 1.52 (95% CI 0.97–2.39, I² = 0%); no symptomatic intracranial haemorrhage; asymptomatic bleeding 15.9%

Guidelines treat ischaemic stroke within the previous three months as a relative contraindication to intravenous thrombolysis, on the reasoning that recently infarcted tissue will bleed. That reasoning has never had a trial behind it — it is expert consensus. This individual-patient-data meta-analysis assembled what evidence exists: 28 reports describing 63 patients who received repeated thrombolysis for a recurrent stroke within 90 days, with individual data available for 44.

Two-thirds (66.7%) achieved a favourable functional outcome. The median interval between treatments was 7.5 days — these are mostly early recurrences, not patients at the edge of the window. The pooled odds ratio for functional outcome after repeat treatment was 1.52 (95% CI 0.97–2.39) with no heterogeneity, and there was no increase in deterioration between episodes (OR 1.28, 0.75–2.19). Outcome was not related to the interval between treatments, age, sex, stroke aetiology, territory or onset-to-treatment time.

The safety signal is the important one and it is reassuring in a specific way: no symptomatic intracranial haemorrhage occurred after repeat thrombolysis. Asymptomatic intracranial or systemic bleeding was reported in 15.9%, and the 5% fatal events were not neurological. Haemorrhagic and fatal events clustered in cardioembolic and more severe strokes, which is where they cluster in first-time thrombolysis too.

• Treat the interval since the last stroke as one factor in a judgement, not an automatic exclusion.
• Weigh it against the usual determinants — severity, salvageable tissue, aetiology, time from onset.
• Cardioembolic and severe strokes carried the bleeding and fatal events here; be more cautious in exactly those patients.
• Document the reasoning when you treat inside 90 days — the decision is defensible on this evidence but it is a departure from a written contraindication.
• Thrombectomy remains available where a large vessel occlusion is present, and is not subject to this restriction.

Why it matters

The 90-day rule has been keeping eligible patients from reperfusion on the basis of consensus rather than evidence.

Don't overread it

Sixty-three patients drawn from case reports cannot establish safety; this weakens a contraindication, it does not remove one.

The statistics, in plain English

Sixty-three patients across 28 reports is a very small evidence base, and it is built from case reports and series, which are published preferentially when they turn out well. Zero symptomatic haemorrhages in 44 patients is consistent with a true rate anywhere up to about 8% — the absence of events in a small sample bounds the risk loosely rather than establishing safety. The odds ratio of 1.52 with an interval from 0.97 to 2.39 just fails to exclude no effect, and the I-squared of 0% means the studies agreed, not that they were large.

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