Time-Dependent Benefit of IV Thrombolysis Before Thrombectomy

פוסט זה זמין גם ב: עברית

April 23, 2024

Written by Laura Murphy

In patients with anterior circulation large-vessel occlusion (LVO) stroke presenting to thrombectomy capable stroke centers, the benefit of intravascular thrombolysis in the setting of endovascular thrombectomy appears to be time-dependent.

The earlier, the better…
This study included a total of 2,313 patients with anterior circulation large vessel occlusion from the IRIS meta-analysis, which included 6 randomized trials comparing IVT plus thrombectomy vs thrombectomy alone (January 2017 and July 2021, 190 sites, 15 countries). Primary outcome analysis tested the association between allocated treatment (IVT + thrombectomy vs thrombectomy alone) and disability at 90 days using modified Rankin Scale (mRS) score range.

Prior to this study, no randomized trial has demonstrated a benefit of IVT in patients directly admitted to thrombectomy-capable stroke centers undergoing thrombectomy, and the results of the IRIS meta-analysis did not establish non-inferiority  of endovascular treatment alone compared with IVT + thrombectomy (i.e. don’t thrombolyze if thrombectomy is immediately available). This study hypothesized that there is a benefit of IVT + thrombectomy if IVT is administered early.

The benefit of IVT plus thrombectomy decreased with longer times from symptom onset to expected administration of IVT: adjusted common OR for 1-step mRS shift toward improvement was 1.49 (95%CI 1.13 to 1.96) at 1 hour, 1.25 (95%CI 1.04 to 1.49) at 2 hours and 1.04 (95%CI 0.88 to 1.23) at 3 hours. After 2 hours and 20 minutes, the benefit associated with IVT plus thrombectomy was not statistically significant. For every hour of delay, there was a significant reduction in association of IVT + thrombectomy with better outcomes.

One study limitation is that patients were only included if presenting to thrombectomy-capable stroke centers, and the use of admission imaging to exclude patients with likely irreversible infarcts may have influenced the magnitude of observed associations with treatment time, which may not be generalizable to all patients. In addition, almost all patients were treated with alteplase (rather than tenecteplase, which is now more widely being adopted). However, the results are likely clinically meaningful and may help to stratify which patients undergoing thrombectomy are most likely to benefit from IVT.

Finally, early recanalization (absence of treatable occlusion on first angiography or successful reperfusion), occurred more often in patients allocated to IVT + thrombectomy (4.0% vs 1.7% for thrombectomy alone), but the association was stronger in patients treated later from symptom onset, though absolute differences were noted to be small. This unexpected finding runs contrary to the classic concept of infarct progression that has been used to explain time dependency in IVT vs placebo trials.

How will this change my practice?
This study demonstrates that the effect of IVT in patients undergoing thrombectomy is most beneficial when administered early; this can be used as part of the decision-making discussion with both patients and consultants about administration of IV thrombolysis in anterior LVO patients who are eligible for thrombectomy.  I will be on the lookout for additional studies that look at this clinical question and any guideline changes.

Time to Treatment With Intravenous Thrombolysis Before Thrombectomy and Functional Outcomes in Acute Ischemic Stroke: A Meta-Analysis. JAMA. 2024 Mar 5;331(9):764-777. doi: 10.1001/jama.2024.0589. PMID: 38324409; PMCID: PMC10851137.

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