Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

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Objective Electronic Health Record (EHR) systems with computerized physician order entry (CPOE) and condition-specific order sets are intended to standardize patient management and minimize errors of omission. However, the impact of these systems on disease-specific process measures and patient outcomes is not well established. We sought to evaluate the impact of CPOE-EHR implementation on process measures and short-term health outcomes for patients hospitalized with acute ischemic stroke. Methods We conducted a quasi-experimental cohort study of patients hospitalized for acute ischemic stroke with concurrent controls that took advantage of the staggered implementation of a comprehensive CPOE-EHR across 16 medical centers within an integrated healthcare delivery system from 2007 to 2012. The study population included all patients admitted to the hospital from the Emergency Department (ED) for acute ischemic stroke with an initial neuroimaging study within 2.5 hours of ED arrival. We evaluated the association between the availability of a CPOE-EHR and the rates of 1) ED intravenous tissue plasminogen activator (IV tPA) administration, 2) hospital-acquired pneumonia (PNA) and 3) inhospital and 90-day mortality using doubly robust estimation models to adjust for demographics, comorbidities, secular trends, and concurrent primary stroke center certification status at each center. Results Of 10,081 eligible patients, 6,686 (66.3%) were treated in centers after CPOE-EHR had been implemented. CPOE was associated with significantly higher rates of IV tPA administration (rate difference 3.4%, 95% CI; 0.8%, 6.0%) but not with rate differences in PNA or mortality. Conclusions For patient hospitalized for acute ischemic stroke, CPOE use was associated with increased use of IV tPA.