Abstract
The benefits and risks of intravenous thrombolysis (IVT) with alteplase for acute ischemic stroke (AIS) beyond 4.5 h are unclear. Decision-making is further limited by the lack of comparisons between imaging strategies used for patient selection, including magnetic resonance imaging with diffusion-weighted imaging (MRI/DWI) and perfusion-guided approaches such as MRI with perfusion-weighted imaging (MRI/PWI) or computed tomography perfusion (CTP). This study aims to evaluate the efficacy and safety of alteplase administered beyond 4.5 h and to compare MRI/DWI- and perfusion-guided IVT.
Databases were searched for RCTs enrolling AIS patients treated with alteplase beyond 4.5 h. Efficacy outcomes included excellent (mRS 0-1) and favorable (mRS 0-2) functional outcomes at 90 days, and major neurological improvement up to 72 h. Safety outcomes included any intracranial hemorrhage (aICH), symptomatic ICH (sICH), parenchymal hemorrhage (PH), and 90-day mortality.
Seven RCTs comprising 1685 patients were included. There were no differences between imaging strategies in any efficacy or safety outcome. Alteplase administered beyond 4.5 h was associated with higher rates of excellent (RR 1.24; 95% CI 1.12-1.38) and favorable (RR 1.17; 95% CI 1.09-1.26) functional outcomes, and increased major neurological improvement (RR 1.28; 95% CI 1.11-1.49). The risks of aICH (RR, 2.82; 95% CI 1.17-6.80), sICH (RR, 3.31; 95% CI 1.42-7.74), and PH (RR, 2.95; CI 95% 1.33-6.53) were higher in the alteplase group, while mortality showed no difference (RR 1.27; 95% CI 0.91-1.76).
This network meta-analysis did not detect a statistically significant difference between perfusion-guided and DWI/FLAIR mismatch-guided selection; however, this comparison was indirect, based on a limited number of trials, and not powered to demonstrate equivalence, and should not be interpreted as evidence that the two paradigms are interchangeable.