ESOC 2023 | Impact of intravenous thrombolysis on different mechanical thrombectomy techniques

As you know, the SWIFT DIRECT trial was one of the six randomized trials trying to address the question whether we should still administer intravenous thrombolysis to patients who are addressed directly to a thrombectomy capable center. So we know we’re going to go ahead and do thrombectomy because there’s a proximal occlusion, but we don’t know if we still should do intravenous thrombolysis. So SWIFT-DIRECT randomized 408 patients between the two methods and the results were neutral in the sense that it didn’t prove non-inferiority nor superiority of the combined approach, compared to thrombectomy alone. Now for this sub-study, we wanted to address a different question in the sense that the updated ESO recommendations still recommend administering intravenous thrombolysis because there is likely an additional benefit, albeit small. However, some neurointerventionalists do have some concerns regarding thrombectomy performed immediately after thrombolysis because they might fear the clot fragments. They think that sometimes it leads to distal emboli which might need additional device passes leading to a longer thrombectomy and eventually maybe a lower complete recanalization rate.

So what we wanted to do was to answer these questions and basically to determine whether the intravenous thrombolysis has a deleterious effect or not on the technical metrics of the procedure, like the number of passes, like the first pass recanalization rate. And we also wanted to determine if the choice of thrombectomy technique would influence in some way the effect of bridging intravenous thrombolysis. Basically for this substudy we included all the patients in the SWIFT DIRECT trial with a few exceptions. So there were 15 patients who were treated with contact aspiration because it’s important to mention the protocol of the swift direct trial required the use of a stent retriever. So in this study we weren’t able to study the influence of intravenous thrombolysis on contact aspiration. We concentrated on stent retriever, so we included all patients from the SWIFT DIRECT trial except 15 patients out of 408 who were treated with aspiration despite recommendations and seven patients who did not receive mechanical thrombectomy. And then when we had our study population, we divided the patients into four groups depending on the stent retriever thrombectomy technique because as you know, stent retriever thrombectomy can be performed in more than one way depending on the use or not of an additional contact aspiration catheter or a balloon guide catheter. So we divided the patients into four groups and then we performed two analyses. The first analysis was an interaction analysis between the choice of first line technique and the effects of bridging thrombolysis. And the secondary analysis, for this part, because this is a first line technique sub-study, we wanted to compare the first line techniques between themselves. So we compared the four different methods to use a stent retriever for safety and efficacy outcomes.

For the primary analysis, we basically wanted to determine whether the choice of thrombectomy technique would influence the effect of bridging intravenous thrombolysis. We did not find any significant interaction. That means whatever stent retriever thrombectomy you choose to do during thrombectomy, the effect of thrombolysis on the final outcomes, whether it’s efficacy or safety, will not be altered or changed. However, in doing this analysis we did observe an interesting and relevant result because patients who did receive intravenous thrombolysis had significantly higher rates of first pass reperfusion, TICI 2c-3. And this was our primary outcome in this sub-study. And we verified this result in the sensitivity analysis by including all patients in the study and by accounting for missing data with multiple imputation and these results stay valid so patients who received intravenous thrombolysis have a higher chance of first pass reperfusion when they go to thrombectomy. And in addition to that, they also fare better on several secondary outcomes like for example, final TICI 2b-3 or TICI 2c-3 reperfusion, and also 90 days clinical outcome.

So this was the primary analysis and for the secondary analysis we compared the four stent retriever methods. So basically the four groups were balloon guide catheter, contact aspiration, and stent retriever. The second was contact aspiration and stent retriever. The third was balloon guide and stent retriever, and the fourth was stent retriever alone without aspiration or balloon guide. What we observed in this secondary analysis was that the patients who were treated using a balloon guide and a stent retriever without a distal aspiration catheter fared better than the other three groups, in terms of recanalization. They had less intracranial hemorrhage at 24 hours and improved clinical outcome.

This study is actually in the same line with another sub-study from one of the other randomized trial which was the SKIP trial. And they also find that patients who are treated with a stent retriever have higher chance of first pass perfusion if they receive thrombolysis. However, there is there are two other studies with kind of discordant results. There was a sub-analysis from the MR CLEAN-NO IV randomized trial and there was also a sub-analysis from the COMPASS trial and in these studies the authors did not find a significantly different first pass reperfusion rate on stent retriever patients. So overall two positive studies for stent retriever thrombectomy and two negative studies. We weren’t able to address the influence of intravenous thrombolysis on aspiration, but some of these studies that I mentioned did look at that. And there again we have some conflicting results. One study found that patients treated with aspiration who received thrombolysis fared better and the other they fared worse. Overall, we think that our study has some advantages compared to the others. Because one, the dataset was very good. So patients were randomized for thrombolysis or not. Two, the study was consistently performed with stent retrievers. So this ensures that our dataset is consistent. And third, we also looked at the different stent retriever sub-techniques. So we feel that there is a clear signal that patients who receive thrombolysis and then receive thrombectomy with stent retrievers fare better compared to without thrombolysis. But of course the ideal would be to perform this analysis again. Um, so as you know there is the IRIS collaboration that has already published initial results. So basically this is a patient level pooled analysis from all the six randomized trials. So maybe one option would be in the future to do a comprehensive analysis on this dataset which comprises more than 2000 patients.