In patients with acute ischemic stroke, the use of thrombolysis in the late window of 4.5 to 9 hours after symptom onset was not associated with an increase in clot migration that would cause reduced clot accessibility to endovascular therapy, a new analysis from the EXTEND trial shows.
“There was no significant difference in the incidence of clot migration leading to clot inaccessibility in patients who received placebo or [intravenous (IV)] thrombolysis,” the authors report.
“Our results found no convincing evidence against the use of bridging thrombolysis before endovascular therapy in patients with acute ischemic stroke who present outside the 4.5-hour window,” they conclude.
“This information is important because it provides some comfort for neuro-interventionists that IV thrombolysis does not unduly increase the risk of clot migration,” senior author, Bernard Yan, DMedSci, FRACP, told Medscape Medical News.
The study was published online in Stroke on February 16.
The Australian researchers explain that endovascular thrombectomy is the standard of care in patients presenting with acute ischemic stroke caused by large vessel occlusion, and current treatment guidelines recommend bridging thrombolysis for all patients receiving thrombectomy within the 4.5-hour time window.
While thrombectomy is also recommended in selected patients up to 24 hours postonset of symptoms, it remains unclear whether thrombolysis pretreatment should be administered in this setting.
One of the issues that might affect use of thrombolysis is distal clot migration. As proximal clot location is a crucial factor determining suitability for endovascular clot retrieval, distal migration may prevent successful thrombectomy, they note.
“Clot migration can happen any time and makes life more difficult for the neuro-interventionist who performs the endovascular clot retrieval,” added Yan, who is a neurologist and neurointerventionist at the Royal Melbourne Hospital, Australia.
In the current paper, the researchers report a retrospective analysis of data from the EXTEND trial of late thrombolysis, defined as 4.5 to 9 hours after symptom onset, to investigate the association between thrombolysis and clot migration leading to clot irretrievability.
The analysis included a total of 220 patients (109 patients in the placebo group and 111 in the thrombolysis group).
Results showed that retrievable clot was seen on baseline imaging in 69% of patients in the placebo group and 61% in the thrombolysis group. Clot resolution occurred in 28% of patients in the placebo group and 50% in the thrombolysis group.
No significant difference was observed in the incidence of clot migration leading to inaccessibility between groups. Clot migration from a retrievable to nonretrievable location occurred in 19% of the placebo group and 14% of the thrombolysis group, with an odds ratio for clot migration in the thrombolysis group of 0.70 (95% confidence interval, 0.35 – 1.44). This outcome was consistent across subgroups.
The researchers note that, to their knowledge, this is the first randomized controlled study to assess the effect of thrombolysis on clot migration and accessibility in an extended time window.
They acknowledge that a limitation of this study is that they only assessed clot migration from a retrievable to a nonretrievable location; therefore, the true frequency of any clot migration occurring was likely to be higher, and this could explain why other reports have found higher odds ratios of clot migration.
But they point out that they chose to limit their analysis in this way specifically to guide decision-making regarding bridging thrombolysis incorporating endovascular therapy in the extended time window.
“The findings of this study are highly relevant in the current clinical environment where there are multiple ongoing trials looking at removing thrombolysis pretreatment within the 4.5-hour time window in thrombectomy patients,” the authors write.
“We have demonstrated that thrombolysis in the 4.5- to 9-hour window is not associated with reduced clot accessibility, and this information will be useful in future trial designs incorporating this extended time window,” they add.
Commenting on the study for Medscape Medical News, Michael Hill, MD, University of Calgary, Canada, said: “Thrombus migration does happen and is likely part of the natural history of ischemic stroke which may be influenced by therapeutics such as thrombolysis. This paper’s top-line result is that thrombus migration occurs in both treated and untreated groups — and therefore that this is really an observation of natural history.”
Hill says that, at present, patients should be treated with thrombolysis before endovascular therapy if they are eligible and these results do not change that recommendation.
“The results of the ongoing trials comparing direct thrombectomy with thrombolysis plus thrombectomy will help to understand the potential clinical outcome relevance of this phenomenon,” he added.
The EXTEND trial was supported by grants from the Australian National Health and Medical Research Council of Australia and the Commonwealth Scientific and Industrial Research Organization Flagship Program.
Yan reported no relevant financial relationships.
Stroke. 2021. Published online February 16. Abstract.