2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association

Summary Background Recombinant tissue plasminogen activator (rt-PA, alteplase) improved functional outcome in patients treated soon after acute ischaemic stroke in randomised trials, but licensing is restrictive and use varies widely. The IST-3 trial adds substantial new data. We therefore assessed all the evidence from randomised trials for rt-PA in acute ischaemic stroke in an updated systematic review and meta-analysis. Methods We searched for randomised trials of intravenous rt-PA versus control given within 6 h of onset of acute ischaemic stroke up to March 30, 2012. We estimated summary odds ratios (ORs) and 95% CI in the primary analysis for prespecified outcomes within 7 days and at the final follow-up of all patients treated up to 6 h after stroke. Findings In up to 12 trials (7012 patients), rt-PA given within 6 h of stroke significantly increased the odds of being alive and independent (modified Rankin Scale, mRS 0–2) at final follow-up (1611/3483 [46·3%] vs 1434/3404 [42·1%], OR 1·17, 95% CI 1·06–1·29; p=0·001), absolute increase of 42 (19–66) per 1000 people treated, and favourable outcome (mRS 0–1) absolute increase of 55 (95% CI 33–77) per 1000. The benefit of rt-PA was greatest in patients treated within 3 h (mRS 0–2, 365/896 [40·7%] vs 280/883 [31·7%], 1·53, 1·26–1·86, p<0·0001), absolute benefit of 90 (46–135) per 1000 people treated, and mRS 0–1 (283/896 [31·6%] vs 202/883 [22·9%], 1·61, 1·30–1·90; p<0·0001), absolute benefit 87 (46–128) per 1000 treated. Numbers of deaths within 7 days were increased (250/2807 [8·9%] vs 174/2728 [6·4%], 1·44, 1·18–1·76; p=0·0003), but by final follow-up the excess was no longer significant (679/3548 [19·1%] vs 640/3464 [18·5%], 1·06, 0·94–1·20; p=0·33). Symptomatic intracranial haemorrhage (272/3548 [7·7%] vs 63/3463 [1·8%], 3·72, 2·98–4·64; p<0·0001) accounted for most of the early excess deaths. Patients older than 80 years achieved similar benefit to those aged 80 years or younger, particularly when treated early. Interpretation The evidence indicates that intravenous rt-PA increased the proportion of patients who were alive with favourable outcome and alive and independent at final follow-up. The data strengthen previous evidence to treat patients as early as possible after acute ischaemic stroke, although some patients might benefit up to 6 h after stroke. Funding UK Medical Research Council, Stroke Association, University of Edinburgh, National Health Service Health Technology Assessment Programme, Swedish Heart-Lung Fund, AFA Insurances Stockholm (Arbetsmarknadens Partners Forsakringsbolag), Karolinska Institute, Marianne and Marcus Wallenberg Foundation, Research Council of Norway, Oslo University Hospital.

To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset. We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved. Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile. For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.

Early mobilisation after stroke is thought to contribute to the effects of stroke-unit care; however, the intervention is poorly defined and not underpinned by strong evidence. We aimed to compare the effectiveness of frequent, higher dose, very early mobilisation with usual care after stroke.