New 'Wake-up' Stroke Analysis Strengthens Case for Thrombolysis

More tyranny of low expectations on full display. 

New 'Wake-up' Stroke Analysis Strengthens Case for Thrombolysis

Evidence supporting the use of thrombolysis for selected stroke patients(YOU need to have the right stroke to get treated properly. YOUR RESPONSIBILITY! You don't want to challenge your stroke team with real world strokes, just those that have been successfully researched.)  with unknown time of onset has been strengthened with data from a new individual patient meta-analysis.

The meta-analysis combined data from four clinical trials that included a total of 483 patients with stroke of unknown time of onset. MRI or CT-perfusion imaging was used to identify those patients with salvageable brain tissue. They had been randomly assigned to receive either thrombolysis with intravenous tissue plasminogen activator (tPA, alteplase) or placebo/standard of care.

Results showed that use of intravenous alteplase resulted in better functional outcome, as measured on Modified Rankin Scale (mRS), at 90 days. Although there was an increase in risk for symptomatic intracranial hemorrhage and more deaths occurred among patients treated with alteplase than placebo, there were fewer cases of severe disability or death.

Dr Götz Thomalla

The new data were presented by Götz Thomalla, MD, University Medical Center Hamburg, Germany, at the European Stroke Organisation–World Stroke Organization (ESO-WSO) Conference 2020 on November 8. They were also simultaneously published online in The Lancet.

"These results provide level 1a evidence for the use of MRI or CT-perfusion imaging to guide treatment with intravenous alteplase in unknown onset stroke," Thomalla concluded.

He explained to Medscape Medical News that alteplase is not approved for treating stroke of unknown time of symptom onset, but American Heart Association/American Stroke Association guidelines and updated ESO guidelines recommend its use on the basis of results of the WAKE-UP trial.

"This meta-analysis refutes formal doubts resulting from the fact that previously, just a single trial (WAKE-UP) demonstrated the benefit of intravenous alteplase in unknown onset stroke," Thomalla said. "The meta-analysis, based on four trials, now provides level 1a evidence, which is a clear basis for guideline recommendations."

Moreover, the large number of patients enabled subgroup analyses, which did not identify any treatment heterogeneity for relevant subgroups. "To summarize: intravenous alteplase guided by MRI or perfusion CT is effective in unknown onset stroke across all subgroups, including [those based on] age, severity, and vessel occlusion," he added.

In an ESO-WSO press conference at which the meta-analysis was discussed, Patrik Michel, MD, Lausanne University Hospital, Lausanne, Switzerland, who was not involved in the study, said: "This is very important data, given that 20% to 25% of ischemic stroke patients have an unknown time of symptom onset. It shows us who will benefit from thrombolysis and when, based on advanced imaging."

Asked how many of the patients with unknown time of stroke onset may be eligible for thrombolysis, Thomalla estimated that about 1 in 3 of such patients could now be considered. "In the WAKE-UP trial, we screened all wake-up patients with MRI and were able to randomize one third of them. But the meta-analysis included trials with two different technologies ― MRI and CT perfusion ― and they are not completely overlapping, so using either of these criteria could extend the number of patents eligible," he noted.