A recent analysis of data from the WAKE-UP trial suggests that intravenous thrombolysis with alteplase benefits patients with unknown-onset ischemic stroke who present with vessel occlusion. The study, a sub-analysis of the multicenter, randomized, placebo-controlled WAKE-UP trial, investigated whether MRI-guided thrombolysis with alteplase improves outcomes in this patient subgroup.
The WAKE-UP trial randomized patients with acute ischemic lesions visible on MRI diffusion-weighted imaging, but without marked parenchymal hyperintensity on fluid-attenuated inversion recovery images, to either intravenous alteplase or placebo. The primary endpoint was a favorable outcome, defined as a modified Rankin Scale score of 0-1 at 90 days post-stroke. This sub-analysis specifically examined the interaction between vessel status and treatment effect.
The results, published recently, included 185 patients with a mean age of 64.5 years, of whom 46% were female. The median NIH Stroke Scale score was 9, and the median time between last seen well and MRI was 10.26 hours. Among these patients, 98 (20%) had large vessel occlusion (LVO), defined as occlusion of the internal carotid artery, middle cerebral artery trunk, or a combination thereof.
Alteplase Improves Outcomes in AVO Patients
The analysis revealed that in patients with any vessel occlusion (AVO), a favorable outcome was observed in 30 of 94 patients (31.9%) in the alteplase group, compared to 18 of 91 patients (19.8%) in the placebo group. This resulted in an adjusted odds ratio (aOR) of 2.04 (95% CI: 1.00-4.18), indicating a statistically significant benefit from alteplase.
Trend Towards Benefit in LVO Patients
In the subgroup of patients with LVO, a favorable outcome was observed in 16 of 53 patients (30.2%) in the alteplase group and 7 of 44 patients (15.9%) in the placebo group. The adjusted odds ratio was 2.08 (95% CI: 0.71-6.10). While this trended towards a benefit, it did not reach statistical significance.
Implications for Clinical Practice
"Although the WAKE-UP study was not powered to demonstrate treatment efficacy in patient subpopulations, this subgroup analysis points to a benefit of MRI-guided thrombolysis in patients with unknown-onset ischemic stroke, independent of vessel occlusion," the researchers noted. The study provides Class II evidence supporting the use of MRI-guided intravenous tissue plasminogen activator in patients with unknown-onset ischemic stroke and AVO to improve outcomes.
The findings suggest that MRI-guided thrombolysis with alteplase can be beneficial for patients with unknown-onset ischemic stroke, regardless of vessel occlusion status. However, the authors caution that further research is needed to confirm these findings in larger, dedicated studies.
