While much-needed improvements to existing triage and transport protocols for acute stroke patients were a leading topic of focus on World Stroke Day (29 October 2022), the World Stroke Congress (WSC; 26–29 October, Singapore) programme saw stroke interventions themselves thrust into the spotlight, with much first-time data being presented on mechanical thrombectomy and intravenous thrombolysis (IVT) treatments alike.
Recent results from the MR CLEAN-LATE trial, which studied the efficacy and safety of thrombectomy—also referred to as endovascular therapy (EVT)—for acute ischaemic stroke in the anterior circulation 6–24 hours after symptom onset or last seen well, delivered by Susanne Olthuis (Maastricht University, Maastricht, The Netherlands), were among these presentations. In the trial, there was a 1.7 times higher chance for better functional outcome in patients who had collateral flow seen on imaging and treated with EVT, Olthuis reported.
Wim van Zwam (Maastricht University), who is also part of the MR CLEAN-LATE team, added: “MR CLEAN-LATE showed clear benefit for patients treated with EVT beyond the six-hour time window when selected on presence of collaterals only. This will open up these treatments in centres currently not able to perform CT [computed tomography] perfusion, will expand the indication beyond CT perfusion, and may speed up decision-making in centres currently using core and penumbra thresholds.”
In a social media post during WSC 2022, Tudor Jovin (Cooper University Health Care, Camden, USA) described these MR CLEAN-LATE data as “another win for the democratisation of thrombectomy”.
Further thrombectomy data
Following this, Yvo Roos (Amsterdam UMC, Amsterdam, The Netherlands) and Urs Fischer (University Hospital of Bern, Bern, Switzerland) presented pooled analyses of individual patient data from six randomised trials that compared direct mechanical thrombectomy against IVT plus thrombectomy (bridging thrombolysis), and found that direct thrombectomy is not non-inferior to bridging thrombolysis at a 5% margin. The researchers reported that IVT prior to mechanical thrombectomy is associated with a higher chance of successful reperfusion—but at the cost of a higher chance of any intracranial haemorrhage (ICH).
Another presentation saw results delivered from the ENCHANTED2 trial. This multicentre, prospective study showed that intensive blood pressure control (target systolic blood pressure [SBP] ≤120mmHg) in patients undergoing mechanical thrombectomy led to adverse effects, with a higher likelihood of poor functional outcome on the modified Rankin Scale (mRS) and more early neurological deterioration compared to less intensive blood pressure management (target 140–180mmHg) in the control arm.
Craig Anderson (The George Institute for Global Health, Sydney, Australia), who disclosed these findings as principal investigator of the study, stated: “While our study has now shown intensive blood pressure control to a systolic target of less than 120mmHg to be harmful, the optimal level of control is yet to be defined.”
Elsewhere, in the EXCELLENT registry, 46.8% of patients achieved good clinical outcome following treatment with the Embotrap revascularisation device (Cerenovus) as a first-line therapy. According to Werner Hacke (University of Heidelberg, Heidelberg, Germany), who presented these results, evaluation of clot composition showed that the percentages of red blood cell and platelet content were strong predictors of clinical and recanalisation outcomes.
In a pre-planned post-hoc analysis of the RESILIENT trial—a study set up to compare stent-retriever treatment and/or thromboaspiration versus best medical therapy for large vessel occlusion stroke—patients treated in the randomisation phase did not have a better outcome at 90 days when compared to ‘roll-in phase’ patients. Sheila Martins and Arthur Pille (both Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil) presented these findings, noting during a WSC 2022 session that the two likely reasons for this being the main finding were the strong effect of endovascular treatment, and good training before and during the roll-in period.
Late-breaking lytics research
Multiple studies investigating the use of tenecteplase as a newer-generation alternative to alteplase in IVT were also presented to attendees, with Mohammed Almekhlafi (University of Calgary, Calgary, Canada) delivering data from the AcT trial, and Vignan Yogendrakumar (Royal Melbourne Hospital, Melbourne, Australia) showcasing a pooled analysis of the Melbourne Stroke Registry, EXTEND-IA and EXTEND-IA TNK trials.
“In a [post-hoc] sub-analysis of the AcT trial, tenecteplase had similar rates of favourable functional outcome and reperfusion prior to thrombectomy,” noted Bruce Campbell (University of Melbourne, Melbourne, Australia). “In a pooled analysis of EXTEND-IA TNK and Australian state-wide registry data, tenecteplase demonstrated increased rates of reperfusion prior to thrombectomy compared to alteplase across a spectrum of time from lytic to angiography up to four hours. Patients who achieved reperfusion prior to thrombectomy had improved functional outcomes compared to those who achieved reperfusion after thrombectomy.
“[…] The differences in time from lytic administration to angiography between the two studies were thought likely to be contributing to the difference in results, as AcT almost exclusively included patients presenting to comprehensive stroke centres with rapid workflow from lytic to arterial access, whereas the Australian data included patients transferred between hospitals.”
A late-breaking clinical trials session saw further AcT data presented, with Dariush Dowlatshahi (University of Ottawa, Ottawa, Canada) reporting that—across more than 1,500 analysed patients—every 30-minute delay in onset-to-needle time was associated with a 9% decrease in the odds of achieving an mRS score of 0–1, while every five-minute delay in door-to-needle time was associated with a 3% reduction in the odds of mRS 0–1. Thus, the researchers concluded that, just as with alteplase, faster treatment leads to better clinical outcomes when acute ischaemic stroke patients are administered intravenous tenecteplase.
During a second late-breaking trials session, a pooled analysis of the NOR-TEST 1 and NOR-TEST 2 trials, both of which saw patients randomised to receive either 0.4mg/kg of tenecteplase or the standard 0.9mg/kg dose of alteplase, was presented by Vojtech Novotny (Haukeland University Hospital, Bergen, Norway). The key finding here was that, for ischaemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score ≥6, the researchers determined no difference in efficacy of the two thrombolytic agents. However, mortality rates were higher in the tenecteplase group, leading them to conclude that a lower dose of tenecteplase should be considered in future studies.
Finally, Nadinda van der Ende (Erasmus MC University Medical Center, Rotterdam, The Netherlands) delivered data from the DUMAS trial at WSC 2022, with dual thrombolysis therapy with pro-urokinase and alteplase demonstrating a similarly low rate of ICH compared to alteplase alone (13% vs 14%, respectively).