Stroke Thrombectomy Beyond the 24-Hour Window: Study Keeps the Door Open

Endovascular thrombectomy (EVT) benefited select stroke patients presenting beyond 24 hours of the time they were last known well, a small observational cohort study showed.

Compared with such very late-presenting stroke patients receiving medical management alone, those selected for EVT were more likely to achieve functional independence at 90 days (38% vs 10%, adjusted OR 4.56, 95% CI 2.28-9.09), according to SELECT Late study investigators led by Amrou Sarraj, MD, of Case Western Reserve University in Cleveland.

The between-group difference in functional independence, defined by modified Rankin Scale scores of 0-2, persisted after propensity score matching by clinical characteristics, CT findings, and perfusion parameters (45% vs 21%, adjusted OR 4.39, 95% CI 1.04-18.53), study authors reported in JAMA Neurology.

As for safety, EVT was associated with reduced mortality (26% vs 41%, adjusted OR 0.49, 95% CI 0.27-0.89) but more symptomatic intracranial hemorrhage (sICH) at 24 hours (10.1% vs 1.7%, adjusted OR 10.65, 95% CI 2.1-51.69).

“Our data demonstrated that EVT is feasible and may improve outcomes in very-late window patients, albeit with increased risk of hemorrhage,” Sarraj and colleagues wrote. “This finding, along with evidence of viable ischemic penumbra beyond 24 hours and subsequent infarct progression with poor clinical outcomes, may open doors for EVT being potentially offered to a carefully selected group of patients.”

While the findings suggested higher probability of benefit in patients with favorable imaging characteristics, “the observational study design cannot exclude a benefit of EVT vs medical therapy in any subgroup,” they noted.

In the last decade, EVT has transformed therapy for patients with large vessel occlusion strokes. The American Heart Association/American Stroke Association increased the pool of EVT candidates in 2018 by widening the recommending treatment window for EVT from 6 hours up to 24 hours after the patient was last known well. This was based on better identification of people with good imaging profiles, suggestive of salvageable brain tissue, in the DAWN and DEFUSE 3 late-window trials.

Still, timely treatment remains important, as every hour of EVT delay translated to a loss of 0.81 healthy life-years in one meta-analysis.

In the present report from SELECT Late, most patients treated with EVT beyond 24 hours had good imaging characteristics. Over 80% showed a presence of mismatch among those with perfusion imaging.

Predictors of that feared complication of EVT, sICH, were longer times from last known well to procedure and Alberta Stroke Program Early CT scores in the 0-5 range.

“Hypothetically, an increasing risk of sICH may outweigh potential benefit in patients presenting very late with significant ischemic changes and requires further evaluation in prospective studies,” Sarraj’s group wrote.

Meanwhile, they suggested, “Considerations of patient-level clinical and imaging characteristics and a thorough discussion with patients and their families about the balance of risks and benefits of EVT is required when deciding whether to offer EVT beyond 24 hours.”

The retrospective cohort study included 301 patients (median age 69 years, about half women) presenting more than 24 hours after last known well during the period from July 2012 through December 2021 at 17 high-volume stroke centers across the U.S., Spain, Australia, and New Zealand. Participants had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment).

This very late-presenting cohort had wake-up stroke in 20% of cases; almost 80% had unwitnessed stroke onset.

Of the cohort, the 61% received EVT and 39% got medical management alone. Those selected for EVT tended to have lower stroke severity and earlier arrival to an EVT-capable center.

IV thrombolysis was administered to 4% of patients in the EVT group and 5% of those receiving medical management.

Ultimately, the study was likely subject to various selection biases that affected results, despite the investigators’ attempts at adjustment.

The researchers acknowledged that prospective studies are warranted for confirmation of their findings, although supported by prior exploratory studies on EVT beyond 24 hours. A randomized trial has not been conducted for stroke patients presenting beyond 24 hours and would be challenging to accomplish, they added.

“Patients with a very extended time since they were last known to be well have a wide range of true onset times and therefore considerable heterogeneity. These patients represent a very small portion of acute ischemic stroke presentations in clinical practice, which may pose logistic challenges for conducting a randomized clinical trial,” according to Sarraj and colleagues.