European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke

Abstract

Intravenous thrombolysis is the only approved systemic reperfusion treatment for patients with acute ischaemic stroke. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions with regard to intravenous thrombolysis for acute ischaemic stroke. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Expert consensus statements were provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high quality evidence to recommend intravenous thrombolysis with alteplase to improve functional outcome in patients with acute ischemic stroke within 4.5 h after symptom onset. We also found high quality evidence to recommend intravenous thrombolysis with alteplase in patients with acute ischaemic stroke on awakening from sleep, who were last seen well more than 4.5 h earlier, who have MRI DWI-FLAIR mismatch, and for whom mechanical thrombectomy is not planned. These guidelines provide further recommendations regarding patient subgroups, late time windows, imaging selection strategies, relative and absolute contraindications to alteplase, and tenecteplase. Intravenous thrombolysis remains a cornerstone of acute stroke management. Appropriate patient selection and timely treatment are crucial. Further randomized controlled clinical trials are needed to inform clinical decision-making with regard to tenecteplase and the use of intravenous thrombolysis before mechanical thrombectomy in patients with large vessel occlusion.

Keywords: Ischaemic stroke; fibrinolysis; recommendations; thrombectomy; thrombolysis.

Figure 1.

Pooled odds ratio for excellent outcome (mRS 0–1) in patients treated with IVT vs. control in the 0–4.5 h time window. The numbers and the ORs for the two time subgroups are from the individual patient data meta-analysis of nine RCTs by Emberson et al.

Figure 2.

Pooled hazard ratio for death at three months in patients treated with IVT vs. control in the 0–4.5 h time window. The numbers and the HRs for the two time subgroups are from the individual patient data meta-analysis of nine RCTs by Emberson et al.

Figure 3.

Pooled odds ratio for excellent outcome (mRS 0–1), good outcome (mRS 0–2) and better functional outcome (common OR across the whole range of the mRS) in patients with ischaemic stroke of 4.5–9 h duration (known onset time) treated with IVT vs. control. This analysis comprises all patients enrolled in the EXTEND, ECASS 4 and EPITHET trials, stratified by time window (4.5–6 h and 6–9 h). The numbers and the ORs for the 4.5–6 h and 6–9 h time windows (adjusted on age and baseline NIHSS score) are taken from the individual patient data meta-analysis of three RCTs (EXTEND, ECASS 4 and EPITHET) by Campbell et al.

Figure 4.

Pooled odds ratio for excellent outcome (mRS 0–1), good outcome (mRS 0–2) and better functional outcome (common OR across the whole range of the mRS) in patients with ischaemic stroke of 4.5–9 h duration (known onset time) treated with IVT vs. control. This analysis is restricted to the subgroup of patients enrolled in the EXTEND, ECASS 4 and EPITHET trials who meet the EXTEND mismatch criteria detected by automated software. The numbers and the ORs for the 4.5–6 h and 6–9 h time windows (adjusted on age and baseline NIHSS score) are taken from the individual patient data meta-analysis by Campbell et al.

Figure 5.

Pooled odds ratio for excellent outcome (mRS 0–1) in ‘unselected’ patients with ischaemic stroke of < 4.5 h duration, treated with tenecteplase (0.25 or 0.4 mg/kg) vs. alteplase (0.9 mg/kg).

Figure 6.

Pooled odds ratio for sICH in ‘unselected’ patients with ischaemic stroke of < 4.5 h duration, treated with tenecteplase (0.25 or 0.4 mg/kg) vs. alteplase (0.9 mg/kg).

Figure 7.

Pooled odds ratio for excellent outcome (mRS 0–1) and better functional outcome (common OR across the whole range of the mRS) in patients with ischaemic stroke of < 4.5 h duration who have documented vessel occlusion and were randomized to IVT with tenecteplase 0.25 mg/kg vs. IVT with Alteplase 0.9 mg/kg. The study by Bivard et al. is a pooled patient subgroup analysis of the TAAIS and ATTEST⁴⁸ randomized trials. The ORs from EXTEND IA TNK were adjusted on age and baseline NIHSS score.

Figure 8.

Pooled odds ratio for excellent outcome (mRS 0–1) in patients randomized to ultrasound augmentation of IVT vs. IVT alone. All patients received IVT with alteplase.

Figure 9.

Pooled odds ratio for favourable outcome* in patients with ischaemic stroke of < 4.5 h duration randomised to with IVT vs. control, stratified by the extent of early ischaemic change on baseline CT (> 1/3 vs. < 1/3 of middle cerebral artery territory). Random effects meta-analysis, based on data from von Kummer et al., Patel et al. and IST-3 subgroup analyses. *Favourable outcome at 3–6 months refers here to Oxford Handicap Scale 0–2 at six months in IST-3 and mRS 0–1 at three months in NINDS and ECASS 1. EIC denotes early ischaemic changes on baseline CT scan. There was no significant interaction between the extent of early ischemic changes (> 1/3 vs. < 1/3 of the MCA territory) and the effect of IVT on favourable outcome (P for interaction = 0.67).

Figure 10.

Pooled odds ratio for death at three months in patients with ischaemic stroke of < 4.5 h duration randomised to IVT vs. control, stratified by the extent of early ischaemic change on baseline CT (> 1/3 vs. < 1/3 of middle cerebral artery territory). Random effects meta-analysis, based on data from von Kummer et al. and Patel et al. EIC denotes early ischaemic changes on baseline CT scan. There was a significant interaction between the extent of early ischemic changes (> 1/3 vs. < 1/3 of the MCA territory) and the effect of IVT on death at three months (P for interaction = 0.005).