UK Stroke Forum 2025 | Intra-arterial thrombolysis after successful thrombectomy recanalization: review and meta-analysis

It’s my pleasure to introduce our recent work about the problem of hypoperfusion despite recanalization. And this is the result of a systematic review and meta-analysis of a randomized clinical trial of intra-arterial thrombolysis as an adjunctive to successful recanalization. And as we all know that acute ischemic stroke can be effectively treated by endovascular thrombectomy, but unfortunately, there’s less than 50% of patients can achieve the excellent functional outcome and the mismatch between the high rate of recanalization and the relatively low excellent functional recovery can be attributable to lots of aspects and which has been discussed in lots of reviews and lots of conferences. And a critical challenge is the incomplete reperfusion, which is persisting in over 30% of patients despite a successful large vessel recanalization. And we now understand that there’s two distinct mechanisms of the incomplete reperfusion after the successful large vessel recanalization. And firstly, that is the territorial hypoperfusion from a distal emboli. And the second is the no-reflow. Maybe the no-reflow phenomenon is more popular in the field of ischemic stroke, but the territorial hypoperfusion was reported by more and more works in this field.

Recently, several randomized clinical trials have been conducted to investigate this question, but their result has been inconsistent. Importantly, the trial adopts different inclusion criteria. Some enrolled patients are achieving eTICI of 2b or better, while other trials enrolled patients with 2c or 3. And these scores are not equivalent in terms of functional outcome and incomplete reperfusion rate. Therefore, we conducted a systematic review and meta-analysis of recent published random clinical trials, which aims to quantify the overall efficacy and the safety of intra-arterial thrombolysis and investigate some outcomes modification by eTICI grid, which may be helpful for the future clinical trial design. And in this systematic review, we included six clinical trials, and they were the CHOICE trial, the POST-UK, POST-TNK, NGO-TNK, PROR, and DATE. And all the trials employed different thrombolytic agents, two used intra-arterial TPA, and three used TNK at a varying dose, and one used urokinase. And critically, for our subgroup analysis, four trials enrolled patients achieving eTICI 2b reperfusion or better, and while two trials enrolled patients with eTICI 2c or 3. And our primary finding of this meta-analysis is that the intra-arterial thrombolysis was significantly associated with the high rate of excellent outcome at 90 days with a risk ratio of 1.24. Importantly, there is a very low heterogeneity across these six studies.

And we also performed a subgroup analysis by the reperfusion grid. And we can see that in patients who achieved eTICI 2b reperfusion or higher, and this part of patients saw the significant benefits from the intra-arterial thrombolysis. And in contrast, in patients with the eTICI 2c or 3 reperfusion, showed only a trend towards benefits with a risk ratio of 1.22, which didn’t reach statistically significant. And while we test for the subgroup interaction, that was not significant. And this patient strongly suggested that patients with incomplete reperfusion, the ones who benefit most from adjunctive intra-arterial thrombolysis are those patients that, who achieved eTICI of 2b or higher, and especially in the subgroup of patients with eTICI 2b. And this also makes pathophysiological sense. If we have better initial tissue level reperfusion, and there is the less thrombotic burden remaining for the thrombolytic agent to address.

And in addition, we also performed ordinal analysis of the mRS distribution that they did show a favorable shift with the intra-arterial thrombolysis. But when we performed a secondary outcome to evaluate whether the intra-arterial thrombolysis can benefit patients who achieved the functional independence, but there was no significant difference. And regarding the safety outcomes, and we found that the intra-arterial thrombolysis is not associated with the symptomatic intracranial hemorrhage rate, and even in patients who received intraarterial thrombosis treatments prior to the endovascular thrombectomy. And above all, in this meta-analysis we found that intra-arterial thrombolysis was associated with a high rate of excellent outcome at 90 days, and a subgroup analysis suggested that only the subgroup of patients with eTICI 2b significantly benefited from the intra-arterial thrombolysis, whereas no significant difference was detected among patients with eTICI 2c or 3, and with, however, a trend towards benefits for patients treated with intra-arterial thrombolysis. And while our analysis showed no significant increase in hemorrhagic complication or mortality, and the limited number of the safety events necessary caution interpretation.

And we all know that the incomplete reperfusion is a very common phenomenon, especially in patients who achieved the large vessel recanalization after thrombectomy. And understanding the mechanism of this phenomenon may help to guide our future management in this phenomenon. And based on our comprehensive review, written in that supplement tool that has been accepted by the Annals of Neurology, and incomplete reperfusion results from multiple mechanisms. And this includes the distal emboli and the residual microthrombi, which are directly taxable by thrombolytic agents. However, other mechanisms include the microvascular dysfunction, the vasospastic constriction, and the progressive microvascular failure that actually continue and can worsen the first 24 hours of the recanalization. And the intra-arterial thrombolysis therapy primarily targets on a mechanical obstruction, but has limited efficacy for microvascular dysfunction. From this meta-analysis, what does this mean for the clinical practice? And I think maybe for the following prospects. Firstly, our funding suggests that the intra-arterial thrombolysis should be strongly considered for patients who achieved eTICI 2b perfusion after thrombectomy. And the patient who achieved the eTICI 2c or 3 may still have a distal emboli not visible on conventional angiograph. And a future trial should incorporate a perfusion imaging to better identify the patients that who can benefit from the intra-arterial thrombolysis therapy after thrombectomy. So, and these are the findings from the meta-analysis of the problem of hypoperfusion despite recanalization.

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