European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke

Abstract

Within the last year, four randomised-controlled clinical trials (RCTs) have been published comparing intravenous thrombolysis (IVT) with tenecteplase and alteplase in acute ischaemic stroke (AIS) patients with a non-inferiority design for three of them. An expedited recommendation process was initiated by the European Stroke Organisation (ESO) and conducted according to ESO standard operating procedure based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. We identified three relevant Population, Intervention, Comparator, Outcome (PICO) questions, performed systematic reviews of the literature and meta-analyses, assessed the quality of the available evidence, and wrote evidence-based recommendations. Expert consensus statements were provided if insufficient evidence was available to provide recommendations based on the GRADE approach. For patients with AIS of <4.5 h duration who are eligible for IVT, tenecteplase 0.25 mg/kg can be used as a safe and effective alternative to alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS of <4.5 h duration who are eligible for IVT, we recommend against using tenecteplase at a dose of 0.40 mg/kg (low evidence, strong recommendation). For patients with AIS of <4.5 h duration with prehospital management with a mobile stroke unit who are eligible for IVT, we suggest tenecteplase 0.25 mg/kg over alteplase 0.90 mg/kg (low evidence, weak recommendation). For patients with large vessel occlusion (LVO) AIS of <4.5 h duration who are eligible for IVT, we recommend tenecteplase 0.25 mg/kg over alteplase 0.9 mg/kg (moderate evidence, strong recommendation). For patients with AIS on awakening from sleep or AIS of unknown onset who are selected with non-contrast CT, we recommend against IVT with tenecteplase 0.25 mg/kg (low evidence, strong recommendation). Expert consensus statements are also provided. Tenecteplase 0.25 mg/kg may be favoured over alteplase 0.9 mg/kg for patients with AIS of <4.5 h duration in view of comparable safety and efficacy data and easier administration. For patients with LVO AIS of <4.5 h duration who are IVT-eligible, IVT with tenecteplase 0.25 mg/kg is preferable over skipping IVT before MT, even in the setting of a direct admission to a thrombectomy-capable centre. IVT with tenecteplase 0.25 mg/kg may be a reasonable alternative to alteplase 0.9 mg/kg for patients with AIS on awakening from sleep or AIS of unknown onset and who are IVT-eligible after selection with advanced imaging.

Keywords: European Stroke Organisation; Intravenous thrombolysis; acute ischaemic stroke; extended time window; large vessel occlusion; recommendations; tenecteplase; wake-up stroke.

Figure 1.

Risk of bias in each randomised controlled clinical trial of IVT with tenecteplase at a dose of 0.25 mg/kg versus IVT with alteplase for AIS patients, with regards to excellent functional outcome at 90 days. Small deviations from intended interventions were noticed: (i) in the AcT trial, where 6/806 patients randomised to the tenecteplase – group and 9/771 randomised to the alteplase – group did not receive the assigned treatment, and (ii) in the TNK-S2B trial, where one patient who was randomised to the alteplase – group received 0.25 mg/kg tenecteplase and one patient who was randomised to 0.25 mg/kg tenecteplase received 0.7 mg/kg tenecteplase.

Figure 2.

Excellent functional outcome (mRS 0–1 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects metaanalysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 3.

Pooled risk difference (in percent) for excellent functional outcome (mRS 0–1 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 4.

Sensitivity analysis for excellent functional outcome (mRS 0–1 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 5.

Sensitivity analysis for pooled risk difference (in percent) for excellent functional outcome (mRS 0–1 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 6.

Sensitivity analysis for excellent functional outcome (mRS 0–1 at 90 days) in unselected patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after excluding the randomised controlled clinical trials that used additional selection criteria (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 7.

Sensitivity analysis for pooled risk difference (in percent) for excellent functional outcome (mRS 0–1 at 90 days) in unselected patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after excluding the randomised controlled clinical trials that used additional selection criteria (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 8.

Good functional outcome (mRS 0–2 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 9.

Pooled risk difference (in percent) for good functional outcome (mRS 0–2 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 10.

Sensitivity analysis for good functional outcome (mRS 0–2 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 11.

Sensitivity analysis for pooled risk difference (in percent) for good functional outcome (mRS 0–2 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 12.

Pooled unadjusted common odds ratio for reduced disability (improvement of a least 1 point on the mRS at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled cOR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; cOdds Ratio: common odds ratio; CI: confidence interval; TE: treatment effect; SE: standard error.

Figure 13.

Major neurological improvement at 24–72 h in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus with intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 14.

Sensitivity analysis for major neurological improvement after excluding EXTEND-IA TNK4 that reported this outcome at 72 h in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 15.

Symptomatic intracranial haemorrhage according to individual study definition in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; sICH: Symptomatic intracranial haemorrhage.

Figure 16.

Sensitivity analysis for symptomatic intracranial haemorrhage according to SITS-MOST definition in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; sICH: Symptomatic intracranial haemorrhage.

Figure 17.

Any intracranial haemorrhage in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; ICH: intracranial haemorrhage.

Figure 18.

Sensitivity analysis for any intracranial haemorrhage in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after excluding TRACE5 that reported this outcome at 90 days (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; ICH: intracranial haemorrhage.

Figure 19.

Any parenchymal haematoma in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus with intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 20.

Extracranial bleeding according to individual study reporting in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects metaanalysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 21.

Sensitivity analysis for major extracranial bleeding in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 22.

All-cause mortality at 3 months in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 23.

Door-to-needle time (in minutes) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus with intravenous thrombolysis with alteplase 0.90 mg/kg (difference of medians, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; IQR: interquartile range.

Figure 24.

Symptom onset-to-needle time (in minutes) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (difference of medians, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; IQR: interquartile range.

Figure 25.

Final infarct volume (in mL) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (mean difference, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; IQR: interquartile range.

Figure 26.

Ischaemic core growth (in mL) within the first 24 h in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (difference of medians, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; IQR: interquartile range.

Figure 27.

Risk of bias in each randomised-controlled clinical trial of IVT with tenecteplase at a dose of 0.4 mg/kg versus IVT with alteplase 0.9 mg/kg for AIS patients, with regards to excellent functional outcome at 90 days.

Figure 28.

Excellent functional outcome (mRS 0–1 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 29.

Pooled risk difference (in percent) for excellent functional outcome (mRS 0–1 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 30.

Sensitivity analysis for excellent functional outcome (mRS 0–1 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 31.

Sensitivity analysis for pooled risk difference (in percent) for excellent functional outcome (mRS 0–1 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus with intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 32.

Good functional outcome (mRS 0–2 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 33.

Pooled risk difference (in percent) for good functional outcome (mRS 0–2 at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 34.

Pooled unadjusted common odds ratio for reduced disability (improvement of at least 1 point on the mRS at 90 days) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled cOR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; cOdds Ratio: common odds ratio; CI: confidence interval; TE: treatment effect; SE: standard error.

Figure 35.

Major neurological improvement within 24 h in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 36.

Sensitivity analysis for major neurological improvement within 24 h, after excluding TNK-S2B that defined major neurological improvement as a NIHSS reduction of at least 8 (in contrast to NOR-TEST and NORT-TEST 2 that accounted as major neurological improvement a NIHSS reduction of at least 4), in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 37.

Pooled risk difference (in percent) for major neurological improvement within 24 h in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 38.

Symptomatic intracranial haemorrhage according to individual study definition in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; sICH: symptomatic intracranial haemorrhage.

Figure 39.

Sensitivity analysis for symptomatic intracranial haemorrhage according to ECASS III definition in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; sICH: Symptomatic intracranial haemorrhage.

Figure 40.

Any intracranial haemorrhage in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; ICH: intracranial haemorrhage.

Figure 41.

Extracranial bleeding in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 42.

All-cause mortality at 3 months in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 43.

Symptom onset-to-needle time (in minutes) in patients with acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.40 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (difference of medians, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; IQR: interquartile range.

Figure 44.

Risk of bias in each randomised-controlled clinical trials-controlled clinical trial of IVT with tenecteplase at a dose of 0.25 mg/kg versus IVT with alteplase for AIS patients with large vessel occlusion, with regard to good functional outcome at 90 days.

Figure 45.

Good functional outcome (mRS 0–2 at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 46.

Pooled risk difference (in percent) for good functional outcome (mRS 0–2 at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −1.3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 47.

Sensitivity analysis for good functional outcome (mRS 0–2 at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 48.

Sensitivity analysis for pooled risk difference (in percent) for good functional outcome (mRS 0–2 at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −1.3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 49.

Sensitivity analysis for good functional outcome (mRS 0–2 at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after excluding TAAIS (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 50.

Sensitivity analysis for pooled risk difference (in percent) for good functional outcome (mRS 0–2 at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg after excluding TAAIS (unadjusted pooled RD, random-effects meta-analysis). The green dashed line indicates the prespecified non-inferiority margin of −1.3%. TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval; mRS: modified Rankin scale.

Figure 51.

Excellent functional outcome (mRS 0–1 at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 52.

Sensitivity analysis for excellent functional outcome (mRS 0–1 at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg, after additional inclusion of all patients returning to baseline mRS (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; mRS: modified Rankin scale.

Figure 53.

Pooled unadjusted common odds ratio for reduced disability (improvement of a least 1 point on the mRS at 90 days) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled cOR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; cOdds Ratio: common odds ratio; CI: confidence interval; TE: treatment effect; SE: standard error.

Figure 54.

Major neurological improvement within 24 h in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 55.

Pooled risk difference (in percent) for major neurological improvement within 24 h in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled RD, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; RD: risk difference; CI: confidence interval.

Figure 56.

Symptomatic intracranial haemorrhage in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval; sICH: Symptomatic intracranial haemorrhage.

Figure 57.

Any parenchymal haematoma in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 58.

All-cause mortality at 3 months in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 59.

Symptom onset-to-needle time (in minutes) in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (mean difference, random-effects meta-analysis).

Figure 60.

Recanalisation before mechanical thrombectomy at first angiographic acquisition or averted mechanical thrombectomy in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.

Figure 61.

Recanalisation within 24 h in patients with large vessel occlusion acute ischaemic stroke of <4.5 h duration treated with intravenous thrombolysis with tenecteplase 0.25 mg/kg versus intravenous thrombolysis with alteplase 0.90 mg/kg (unadjusted pooled OR, random-effects meta-analysis). TNK: tenecteplase; IV: inverse variance; CI: confidence interval.