Intravenous thrombolytic therapy (IV) with recombinant tissue-plasminogen activator (alteplase; 0.9 mg/kg over 1h) is beneficial for acute ischaemic stroke patients with potentially disabling neurological deficits, and without contraindications, when started =4.5h of onset. Benefit is time-dependent: among 1000 patients, IVT =3h lessen long-term disability in 178 patients, between 3-4.5h in 66. IVT under 4.5h is associated with an increase in symptomatic haemorrhage, but not an increase in death or severe disability. Based on trial evidence, IVT =3h is strongly endorsed, and between 3-4.5 hours moderately endorsed, by guidelines on 5 continents. Benefit is evident in patients under and over age 80, and in patients with up to moderate, but not extensive (more than 100 cc), early ischaemic changes on initial CT or MRI. IVT is also beneficial for patients =4.5h after onset with substantial salvageable tissue on penumbral CT or MR imaging. Systems of care should be optimized to start IVT =60m, and optimally =30m, after ED arrival. Large-scale trials are needed to further enhance IVT, testing: faster treatment start in mobile stroke units (mobile CT ambulances): fibrinolytic agent and concomitant lytic-enhancing combinations; bridging neuroprotection and collateral enhancement; and the optimal way to combine intravenous thrombolytic therapy and endovascular mechanical thrombectomy.

Endovascular thrombectomy (EVT) with highly effective reperfusion devices is beneficial for: 1) relatively broadly selected acute ischaemic stroke patients with anterior circulation large vessel occlusions (LVOs) who have failed or are ineligible for intravenous fibrinolysis, up to 7 h after onset; and 2) imaging-selected patients with a favorable penumbral profile (small core and substantial salvageable tissue) 6–24h after onset. Among early-presenting patients, benefit is strongly time-dependent; for every 4 m delay in door-to-reperfusion time, 1 of every 100 patients has a worse disability outcome. Based on the trial evidence, EVT is strongly endorsed by guidelines worldwide. Within the first 7h, benefit is evident in patients under and over age 80, and in patients with up to moderate early ischaemic changes on imaging (ASPECTS 6-10). Systems of care should be optimized to deliver likely LVO patients to endovascular-capable stroke centers, and for procedure start (arterial puncture) within 75m, and optimally within 45m, after ED arrival. Large-scale trials are testing: best prehospital recognition and routing protocols: novel device designs to increase reperfusion rates in large and also medium vessel occlusions; bridging neuroprotection and collateral enhancement; potential benefit in patients with large cores; and best concomitant therapies, including sedation mode and post-procedure blood pressure management.