PT  - JOURNAL ARTICLE
AU  - Tsivgoulis, Georgios
AU  - Katsanos, Aristeidis H.
AU  - Malhotra, Konark
AU  - Sarraj, Amrou
AU  - Barreto, Andrew D.
AU  - Köhrmann, Martin
AU  - Krogias, Christos
AU  - Ahmed, Niaz
AU  - Caso, Valeria
AU  - Schellinger, Peter D.
AU  - Alexandrov, Andrei V.
TI  - Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window
AID  - 10.1212/WNL.0000000000008904
DP  - 2020 Mar 24
TA  - Neurology
PG  - e1241--e1248
VI  - 94
IP  - 12
4099  - http://n.neurology.org/content/94/12/e1241.short
4100  - http://n.neurology.org/content/94/12/e1241.full
SO  - Neurology2020 Mar 24; 94
AB  - Objective To assess the utility of IV thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS) with unclear symptom onset time or outside the 4.5-hour time window selected by advanced neuroimaging.Methods We performed random-effects meta-analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores 0–1), 3-month functional independence (FI; mRS scores 0–2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS scores), symptomatic intracranial hemorrhage (sICH), and complete recanalization (CR).Results We identified 4 eligible randomized clinical trials (859 total patients). In unadjusted analyses, IVT was associated with a higher likelihood of 3-month FFO (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.12–1.96), FI (OR 1.42, 95% CI 1.07–1.90), sICH (OR 5.28, 95% CI 1.35–20.68), and CR (OR 3.29, 95% CI 1.90–5.69), with no significant difference in the odds of all-cause mortality risk at 3 months (OR 1.75, 95% CI 0.93–3.29). In the adjusted analyses, IVT was also associated with higher odds of 3-month FFO (adjusted OR [ORadj] 1.62, 95% CI 1.20–2.20), functional improvement (ORadj 1.42, 95% CI 1.11–1.81), and sICH (ORadj 6.22, 95% CI 1.37–28.26). There was no association between IVT and FI (ORadj 1.61, 95% CI 0.94–2.75) or all-cause mortality (ORadj 1.75, 95% CI 0.93–3.29) at 3 months. No evidence of heterogeneity was evident in any of the analyses (I2 = 0).Conclusion IVT in patients with AIS with unknown symptom onset time or elapsed time from symptom onset >4.5 hours selected with advanced neuroimaging results in a higher likelihood of CR and functional improvement at 3 months despite the increased risk of sICH.AIS=acute ischemic stroke; CI=confidence interval; DWI=diffusion-weighted imaging; ECASS=European Cooperative Acute Stroke Study; EPITHET=Echoplanar Imaging Thrombolytic Evaluation Trial; EXTEND=Extending the Time for Thrombolysis in Emergency Neurological Deficits; FLAIR=fluid-attenuated inversion recovery; FFO=favorable functional outcome; FI=functional independence; IVT=IV thrombolysis; mRS=modified Rankin Scale; OR=odds ratio; RCT=randomized clinical trial; sICH=symptomatic intracranial hemorrhage