Thrombolytic therapy for wake‐up stroke: A systematic review and meta‐analysis

Abstract

Background and purpose According to evidence‐based clinical practice guidelines, patients presenting with disabling stroke symptoms should be treated with intravenous tissue plasminogen activator (IV tPA) within 4.5 h of time last known well. However, 25% of strokes are detected upon awakening (i.e., wake‐up stroke [WUS]), which renders patients ineligible for IV tPA administered via time‐based treatment algorithms, because it is impossible to establish a reliable time of symptom onset. We performed a systematic review and meta‐analysis of the efficacy and safety of IV tPA compared with normal saline, placebo, or no treatment in patients with WUS using imaging‐based treatment algorithms. Methods We searched MEDLINE, Web of Science, and Scopus between January 1, 2006 and April 30, 2020. We included controlled trials (randomized or nonrandomized), observational cohort studies (prospective or retrospective), and single‐arm studies in which adults with WUS were administered IV tPA after magnetic resonance imaging (MRI)‐ or computed tomography (CT)‐based imaging. Our primary outcome was recovery at 90 days (defined as a modified Rankin Scale [mRS] score of 0–2), and our secondary outcomes were symptomatic intracranial hemorrhage (sICH) within 36 h, mortality, and other adverse effects. Results We included 16 studies that enrolled a total of 14,017 patients. Most studies were conducted in Europe (37.5%) or North America (37.5%), and 1757 patients (12.5%) received IV tPA. All studies used MRI‐based (five studies) or CT‐based (10 studies) imaging selection, and one study used a combination of modalities. Sixty‐one percent of patients receiving IV tPA achieved an mRS score of 0 to 2 at 90 days (95% confidence interval [CI]: 51%–70%, 12 studies), with a relative risk (RR) of 1.21 compared with patients not receiving IV tPA (95% CI: 1.01–1.46, four studies). Three percent of patients receiving IV tPA experienced sICH within 36 h (95% CI: 2.5%–4.1%; 16 studies), which is an RR of 4.00 compared with patients not receiving IV tPA (95% CI: 2.85–5.61, seven studies). Conclusions This systematic review and meta‐analysis suggests that IV tPA is associated with a better functional outcome at 90 days despite the increased but acceptable risk of sICH. Based on these results, IV tPA should be offered as a treatment for WUS patients with favorable neuroimaging findings.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial

“…Our trial adds evidence to a previous systematic review and meta-analysis of controlled trials, observational cohort studies and single-arm safety studies which showed no significant difference in functional or safety outcomes between studies that evaluated patients with non-contrast CT, MRI, or CT perfusion prior to treatment. 30 Our trial has several limitations. Based on a revised power estimation, the recruitment target was increased from 500 to 600 patients.…”

“…Denmark: National Coordinator H.K. Christensen Bispebjerg Hospital (30), L. Christensen (PI), K. AEgidius (PI), H.K. Christensen, T. Pihl, C. Fassel-Larsen, A. Hansen, N. Preisler, M. Folke, L. Wassvik.…”

The impact of telemedicine enabled pre-hospital triage in acute stroke – a protocol for a mixed methods systematic review

“…(WUS is defined here as the scenario where a person wakes up with symptoms of stroke having gone to bed previously symptom free, and where their last known well time >4.5 hours prior 12 ).…”

Fibrinólisis intravenosa con alteplasa en un paciente joven con ictus isquémico agudo asociado a coartación de aorta

“…En presencia de un ictus isquemico agudo la evidencia actual avala el tratamiento con activador tisular del plasminógeno intravenoso (alteplasa), dentro de las 4,5 horas del inicio de los sintomas (8).…”