A recent sub-analysis of the SWIFT-DIRECT trial, which is published in the Journal of NeuroInterventional Surgery (JNIS), has found “no evidence” that the effect of bridging intravenous thrombolysis (IVT) on functional independence outcomes is modified by overall or in-hospital treatment delays, indicating that the effect of IVT plus thrombectomy is preserved over time and all IVT-eligible patients should therefore be treated with this combined approach.
However, writing in JNIS, Urs Fischer, Thomas Meinel (both University Hospital of Bern, Bern, Switzerland) and colleagues state that, due to its “low power”, this subgroup analysis “could have missed a clinically important effect”—also noting that “exploratory analysis of secondary clinical outcomes indicated a potentially favourable effect of IVT with shorter in-hospital delays”.
The authors hypothesised that treatment delays might be an ‘effect modifier’ for the risks and benefits of IVT before a mechanical thrombectomy in acute ischaemic stroke patients. To assess this, they used the dataset from the international SWIFT-DIRECT trial, which randomised 408 patients to receive IVT plus thrombectomy, or thrombectomy alone.
Fischer initially presented preliminary results from SWIFT-DIRECT alongside Jan Gralla (University Hospital of Bern, Bern, Switzerland) at the 7th European Stroke Organisation Conference (ESOC 2021; 1–3 September, virtual), with full results being published in The Lancet in July of this year.
In their more recent JNIS sub-analysis, Fischer, Meinel and colleagues set out to assess the relationship between assignment to IVT plus thrombectomy, and expected onset-to-needle (OTN) and door-to-needle (DTN) times, via regression models. Their primary outcome was functional independence at three months—categorised as a score of 0–2 on the modified Rankin Scale (mRS)—while secondary outcomes included mRS shift, mortality, recanalisation rates and (symptomatic) intracranial haemorrhage at 24 hours.
The researchers included 408 patients (median age=72 years, 51.2% female)—207 of these received IVT plus thrombectomy and 201 received thrombectomy alone. The expected median OTN and DTN times were 142 minutes and 54 minutes in the IVT plus thrombectomy group, and 129 minutes and 51 minutes in the thrombectomy-alone group, respectively.
Overall, Fischer, Meinel and colleagues found that OTN times had no significant bearing on functional and safety outcomes, as well as the recanalisation rates, associated with bridging IVT in their sub-analysis. They report similar findings regarding in-hospital delays, as DTN times were not found to have significantly affected functional outcomes following bridging IVT treatments. However, mRS shift and mortality analyses suggested greater benefits when bridging IVT was administered after shorter average in-hospital delays.
The authors note that “good overall data quality” within the context of a prospective, multicentre randomised controlled trial (SWIFT-DIRECT) and a prespecified, deposited statistical analysis plan were among the key strengths of their investigation, but concede that limitations should be considered too—including the fact that the original study was “neither designed nor powered to detect an interaction effect” between treatment delays and bridging IVT outcomes.
“Until further evidence regarding potential heterogeneity of the IVT effect size before mechanical thrombectomy becomes available from individual patient meta-analysis of comparable trials,” Fischer, Meinel and colleagues conclude, “IVT should be given to eligible patients, and neither OTN nor DTN should influence treatment decisions regarding bridging IVT.”