Thrombectomy Benefits LVO Stroke at 2 years

Latest results from the MR CLEAN-LATE trial showed that the benefit of endovascular treatment in late-window patients with large volume occlusion (LVO) acute ischemic stroke selected based on the presence of collateral flow on CT angiography is sustained out to 2 years follow-up.

As reported previously by Medscape Medical News, initial results from the trial showed that endovascular treatment was safe and improved outcomes at 90 days in patients with LVO stroke presenting 6-12 hours after symptom onset identified based on the presence of collateral flow on CT angiography.

Those findings suggested that patient selection in the late window could be primarily based on the presence of collateral flow, rather than advanced imaging, and expanded treatment selection to a larger population.

The new results “highlight a sustained and clinically meaningful improvement in the likelihood of favorable functional outcomes during a 2-year follow-up period,” lead investigator Ilse Huijberts, PhD, Maastricht University Medical Center, Maastricht, the Netherlands, and colleagues wrote. 

The study is thought to be the first to show the effectiveness of collateral-based selection for late-window endovascular treatment of patients with ischemic stroke up to 2 years after randomization. 

“As the selection criteria of the MR CLEAN-LATE trial were simple and pragmatic, these long-term follow-up results further underscore the value of late-window endovascular treatment for a large group of patients,” study authors wrote.

“Furthermore, as collateral-based selection with CT angiography is more widely available than perfusion imaging, these results promote the long-term effectiveness of late-window endovascular treatment in settings with limited access to perfusion imaging,” they added.

The 2-year results from the MR CLEAN LATE trial were published online in The Lancet Neurology on June 20.

Important Follow-Up

MR CLEAN-LATE, conducted at 18 stroke intervention centers in the Netherlands, included 502 patients with an acute ischemic stroke due to a large vessel occlusion in the anterior circulation and at least some collateral flow in the affected middle cerebral artery presenting within 6-24 hours of symptom onset. They were randomized to endovascular treatment or best medical treatment alone (control group).

The main results of the trial, reported in 2022, showed that patients in the intervention group were more likely to show a benefit on the primary endpoint of modified Rankin Scale (mRS) score at 90 days with a significant common odds ratio (OR) of 1.68, meaning that patients treated with endovascular therapy had about a 1.7 times higher chance of achieving a better functional outcome.

By 2 years, data for mRS scores were available for 89% patients in the endovascular treatment group and for 82% patients in the control group. Results showed a median mRS score of 4 at long-term follow-up in the endovascular treatment group vs 6 in the control group. 

The endovascular treatment group demonstrated a shift towards better functional outcomes on the mRS (adjusted common OR, 1.41; 95% CI, 1.00-1.99; P = .049). 

Patients allocated to the endovascular treatment group had significantly higher odds of good functional outcome, but there was no significant difference in excellent functional outcome between the endovascular treatment group and the control group. 

All-cause mortality at 2 years was 34% in the endovascular treatment group and 41% in the control group (adjusted hazard ratio, 0.81; P = .15). 

Major vascular events (transient ischaemic attack, ischaemic stroke, hemorrhagic stroke, and cardiac events) were reported between 90 days and 2 years in 23 patients in the endovascular treatment group and 13 patients in the control group.

“Our study results might be important for prompting and supporting further evaluations of the cost-effectiveness of late-window endovascular treatment,” the authors concluded.

Clinically Meaningful

In an accompanying article, Bruce Campbell, MBBS, Royal Melbourne Hospital, Parkville, Australia, noted that in the magnitude of effect for functional independence in MR CLEAN-LATE was 8%, smaller than observed in the thrombectomy studies performed within 0-6 hours and in the studies using mismatch selection 6-24 hours after stroke onset. 

“However, this absolute difference is clinically meaningful and similar to the benefit reported with late-window intravenous thrombolysis in patients with large vessel occlusion and perfusion mismatch,” he wrote. 

Multiple trials have now examined the role of endovascular thrombectomy in patients with extensive ischemic injury based either on noncontrast CT or perfusion-imaging estimates of ischemic core volume, Campbell added. 

Three studies have extended the time window to 24 hours after stroke onset, and a benefit of thrombectomy was consistently shown in a much broader group of patients with stroke caused by a large arterial occlusion than were included in MR CLEAN-LATE, which mainly enrolled patients with mild ischemic changes on noncontrast CT. 

He noted that, although prognostic, imaging parameters — including ischemic core volume, perfusion mismatch, Alberta Stroke Program Early CT score, and collateral status — were not treatment-effect modifiers in those trials.

“In this context, exclusion of patients with absent collateral flow on single-phase CT angiography, as occurred in MR CLEAN-LATE, might not be justified,” he suggested.

The evidence for treatment benefit of endovascular thrombectomy has grown remarkably in the past decade, Campbell added, although many trials have excluded people with frailty and comorbidity.

“Nonetheless, within the patient groups included in these trials, the results of long-term follow-up after thrombectomy have been consistently reassuring in that the treatment effect seen at 90 days was preserved at 1-2 years,” he added.