Safety and efficacy of repeated intravenous thrombolysis within 3 months for acute ischemic stroke: a systematic review and individual-patient data meta-analysis

Background: Current stroke guidelines consider a previous acute ischemic stroke (AIS) within 3 months a relative contraindication to intravenous thrombolysis (IVT) because of the perceived risk of symptomatic intracranial haemorrhage (sICH). The recommendation is largely based on expert consensus, while growing evidence suggests repeated IVT (RIVT) may be feasible in selected patients. Aims: To systematically review the efficacy and safety of RIVT for recurrent AIS within 90 days of a previous IVT-treated stroke. Results: We performed a systematic review and individual-patient data meta-analysis, including 28 reports (63 patients), with individual patient data available for 44 cases. Overall, 66.7% of patients achieved a favorable outcome, with a 7.5 days median interval between treatments. Meta-analysis showed a non-significant trend toward better functional outcomes after RIVT (pooled OR = 1.52, 95% CI 0.97–2.39; I2 = 0%) and no significant increase in functional deterioration between stroke episodes (pooled OR = 1.28, 95% CI 0.75–2.19; I2 = 0%). Outcomes were not influenced by treatment interval, age, sex, stroke etiology, vascular territory, or onset-to-treatment time. No sICH occurred after RIVT. Asymptomatic intracranial or systemic haemorrhages were reported in 15.9% of patients, while fatal events (5%) were unrelated to neurological complications. Haemorrhagic and fatal events occurred predominantly in patients with cardioembolic and more severe strokes. Conclusions: RIVT within 90 days is a rare event and its efficacy is understudied. It may be a reasonable reperfusion strategy in carefully selected patients with recurrent AIS, suggesting that the interval from the previous stroke should not be considered an isolated exclusion criterion for IVT.