Late-Breaking Science: New data in clot removal, stroke patients with COVID-19

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Late-Breaking Science investigators during Friday’s Closing Main Event reported:

  • Thrombectomy 6-24 hours after stroke onset provides significant patient benefits.
  • Racial, ethnic disparities affect endovascular treatment, outcomes.
  • A novel radially adjustable clot retriever beats standard retrievers in clinical trial.
  • Meta-analysis favors endovascular thrombectomy over standard care for acute vertebrobasilar artery occlusion.
  • COVID-19 patients with stroke are more likely to be older, people who are Black and male; have a longer length of stay; die in the hospital; and have specific metabolic and cardiovascular comorbidities over other COVID-19 patients.

Thrombectomy benefits present 6 to 24 hours after stroke onset

Two randomized trials have shown that thrombectomy in proximal large vessel occlusive stroke is both safe and effective up to 24 hours after last-known well. The Analysis of Pooled Data from Randomized Studies of Thrombectomy More than 6 Hours After Last-Known Well (AURORA) collaboration pooled individual patient data from six prospective thrombectomy trials that randomized patients beyond 6 hours from last-known well to evaluate the safety and outcomes from mechanical clot removal in the 6- to 24-hour time window.

Patients were selected based on the presence of salvageable tissue identified with the use of multiple imaging modalities.

“There is currently a divide in terms of our approach to thrombectomy according to time window,” said Tudor G. Jovin, MD, medical director of Cooper Neurological Institute and chair and chief of neurology at Cooper University Health Care at the Cooper Medical School of Rowan University in Camden, New Jersey. “Existing guidelines use different patient selection criteria for patient presenting between 0 to 6 hours versus 6 to 24 hours from time last seen well. We found that the benefits in terms of reduced disability of thrombectomy extend throughout the 6 to 24 hours epoch.”

The AURORA investigators evaluated disability as measured by the modified Rankin Scale at 90 days. Researchers also evaluated safety based on symptomatic intracerebral hemorrhage and all-cause mortality at 90 days. The combined trials had 266 thrombectomy patients and 239 controls.

Patients who received thrombectomy 6 to 24 hours after stroke had an adjusted odds ratio of 2.54 (p<0.0001) for reduced disability. There was no difference in safety outcomes, 16.5% mortality for thrombectomy versus 19.3% for controls, or for symptomatic intracranial hemorrhage, 5.3% for thrombectomy versus 3.3% for controls.

The treatment effect was stronger in patients randomized 12 to 24 hours after last-known well versus 6 to 12 hours, OR = 5.86 versus 1.76 (p ˂0.0001) mainly due to worse outcomes noted in the late randomized compared to control patients. 

It is not entirely clear why thrombectomy in the later time window has a larger treatment effect. There may be a higher rate of spontaneous recanalization in control patients randomized within 6 to 12 hours versus in those randomized later.

“The most important message is that the benefits of thrombectomy are preserved throughout 24 hours,” Jovin said. “These results should remove any doubt that the benefits of treatment are not as robust in the 16- to 24-hour window compared to earlier. I could see a change in practice for centers that are still reluctant to consider treatment beyond 16 hours from last-known well.”

Racial, ethnic gaps in endovascular therapy utilization, outcomes persist

The publication of clinical trials in 2015 supporting the use of endovascular therapy to treat acute ischemic stroke secondary to large vessel occlusion resulted in improved uptake of this life-saving therapy across racial and ethnic groups. A retrospective analysis found that treatment and outcome gaps are closing but still persist even after multiple trials confirmed the benefits of endovascular thrombectomy (EVT) across broad populations.

“The most promising thing is that these gaps have started to close down,” said Faheem Sheriff, MD, assistant professor of neurology at Texas Tech University Health Sciences Center at El Paso. “We need to more closely look at the remaining gaps and target patients who are disadvantaged.”

Researchers assessed all acute ischemic stroke patients who met recommended time from onset and severity eligibility criteria for EVT in the AHA Get With the Guideline-Stroke database between April 2012 and June 2019. Of 302,965 potentially eligible patients who were admitted within 6 hours of last-known well and met stroke severity criteria (NIH Stroke Scale ˃6), 42,422 patients (14%) received EVT.

Black patients had an odds ratio of 0.68 for receiving EVT compared to Non-Hispanic white patients before 2015. This gap narrowed to 0.83 after 2015 (p for interaction = 0.0187). 

Black, Hispanic and Asian patients had more favorable short-term outcomes than Non-Hispanic white patients, including lower in-hospital mortality or discharge to hospice (Black patients OR 0.60, Hispanic patients OR 0.74, Asian patients OR 0.84) and higher rates of discharge home (Black patients OR 1.10, Hispanic patients OR 1.38, Asian patients OR 1.44). 

This could reflect true outcome differences, Sheriff said, or it could represent sociocultural differences. Previous studies have shown that Non-Hispanic white patients are more likely to withdraw care and choose hospice. 

Ninety-day functional outcomes were highest for Non-Hispanic white patients. The odds for a modified Rankin Score of 0-2 after 2015 were 0.84 for Black patients and 0.8 for Asian patients versus 0.80 and 0.52 respectively before 2015. Differences in 90-day outcomes may represent differences in access to rehabilitation because of geographic location, cost or insurance coverage. 

“Access to care as a result of historic inequalities may be part of the equation as well,” Sheriff said. “Our goal is to reach a common ground where all race and ethnic groups are benefiting from this lifesaving treatment as much as possible.” 

Radially adjustable clot retriever superior to conventional retrievers 

The first multicenter trial of a novel radially adjustable clot retriever found that the Tigertriever is superior to conventional retrievers in both successful reperfusion and a composite safety endpoint of mortality and symptomatic intracranial hemorrhage.

“The Tigertriever has two key advantages over existing stent retrievers,” said Jeffrey L. Saver, MD, FAHA, stroke neurology co-principal investigator. “It is the first radially adjustable device, so the degree to which the stent expands is controlled by the interventionalist. And, unlike several others, it is fully visible on imaging during the procedure.”

Saver is professor and Carol and James Collins Chair of Neurology and director of the comprehensive stroke and vascular neurology program at the David Geffen School of Medicine at University of California in Los Angeles. The neurointerventionalist co-principal investigator is Rishi Gupta, MD, director of neurocritical care at WellStar Neuroscience Institute in Smyrna, Georgia.

The trial treated 160 patients at 17 centers in the U.S. and Israel, 43 patients in a lead-in phase and 117 patients in the main phase. All patients had acute ischemic stroke with NIH Stroke Scale ≥8 due to large vessel occlusion within 8 hours of last-known normal.

The primary efficacy endpoint was successful reperfusion with a maximum of three passes of the Tigertriever. The primary safety endpoint was a composite of all-cause mortality at 90 days and symptomatic intracranial hemorrhage. The comparator was a composite of outcomes from six recent pivotal studies of the Solitaire and Trevo stent retrievers.

The TIGER study showed successful reperfusion in 84.6% of patients in the main study group versus 63.4% for the performance goal derived from conventional stent retrievers (p<0.0001), with a first pass reperfusion rate of 57.8% and a final reperfusion rate after rescue devices of 95.7%. The primary safety endpoint for mortality and symptomatic intracranial hemorrhage was 18.1% for TIGER versus 30.4% for the conventional retriever’s performance goal (p=0.004) with 58% of patients achieving a modified Rankin score of 0-2 at 90 days.

"Tigertriever is highly effective and safe in removing clots in patients with large vessel occlusive strokes who are eligible for mechanical thrombectomy,” said Gupta. “The device has been submitted to the Food and Drug Administration for clearance. It has been used in Europe since 2018.”

The study was published simultaneously in Stroke.

Metanalysis shows benefit of endovascular thrombectomy versus thrombolysis for vertebrobasilar occlusion

A meta-analysis pooling data from two randomized trials demonstrated the benefit of endovascular therapy for treating acute vertebrobasilar artery occlusion (AVBAO). The two trials, BEST and BASICS, were each underpowered and subject to limitations that limited their conclusions.

VERITAS (Vertebrobasilar Occlusion Randomization to Endovascular Reperfusion versus Intravenous Thrombolysis or Medical Treatment Alone Systematic Evaluation) combined patient level data from populations in China (BEST plus Europe and South America (BASICS). The two trials were similar in design, enrollment criteria and primary outcome, said Raoul G. Nogueira, MD, professor of neurology at Emory University School of Medicine and neurovascular director at Grady Memorial Hospital Marcus Stroke & Neuroscience Center. Results from both trials were confusing.

The primary analysis of BEST failed to show benefit for endovascular thrombectomy (EVT) versus standard medical treatment. Fewer than one-third of patients received thrombolysis. A subgroup analysis of crossover patients showed a per-protocol adjusted odds ratio of 2.90 favoring EVT. 

BASICS showed a odds ratio of 1.18 favoring EVT. Most patients received IVT, but a subgroup analysis showed that patients not receiving IVT had better outcomes with best medical management than with EVT. 

“Both trials were underpowered, had poor recruitment and were subject to selection bias,” Nogueira said. “BASICS investigators had to include patients with NIH Stroke Scale (NIHSS) less than 10, diluting the treatment effect and effectively decreasing the sample size by 40%. BEST had too many crossovers and important patient imbalances. It required a meta-analysis to show benefit, or lack of benefit, from EVT in AVBAO.”

VERITAS combined the BEST and BASICS populations for a total of 351 patients, 181 in the EVT arm and 170 in the best medical management control arm, all with a baseline NIHSS ≥10.The primary outcome, a modified Rankin Scale of 0-3, showed an adjusted odds ratio of 1.72 favoring EVT (p= 0.04) by intention to treat analysis. A subgroup analysis favored best medical management for baseline NIHSS 1-9 and EVT for baseline NIHSS ≥10. 

“This adjusted analysis demonstrated a significant improvement in favorable outcomes with EVT for patients with baseline NIHSS ≥10,” Nogueira said. “We should learn more from three trials of EVT in basilar artery occlusion ongoing in China.”

The nexus of stroke and COVID-19

A retrospective analysis of U.S. hospital data provides the first good picture of stroke in patients with COVID-19. The first analysis of the AHA COVID-19 Cardiovascular Disease Registry focused on stroke and found COVID-19 patients with stroke are older than patients without stroke and more likely to be men. COVID-19 patients with stroke also had a longer length of stay and higher in-hospital mortality than those without stroke.

“We know how to diagnose stroke, we know how to treat it, we know diagnosis and treatment are time-sensitive,” said Saate Shakil, MD, cardiology fellow at the University of Washington School of Medicine in Seattle, Washington. “But we don’t know the mechanisms that link COVID-19 and stroke. These data show even if you survive COVID-19 that is severe enough to require hospitalization, there is a very real risk of stroke that could be fatal or cause long-term disability.”

The AHA COVID-19 Cardiovascular Disease Registry has been enrolling hospitalized COVID-19 patients since shortly after the pandemic emerged in the United States in 2020. A total of 21,072 patients with confirmed COVID-19 were admitted to U.S. hospitals in the registry between March and November 2020. Of that cohort, 1.4% (289 patients) had a stroke during hospitalization confirmed by diagnostic imaging.  

Of the stroke patients, 152 (52.6%) had ischemic stroke, 8 (2.8%) had transient ischemic attack (TIA) and 127 (45.2%) had other types of stroke. The mean age of patients with ischemic stroke/TIA was 65 years versus 61 for those without stroke and 101 ischemic stroke/TIA patients (63.1%) were male. Patients in the group with ischemic stroke and TIA were also more likely to have diabetes, hypertension, coronary artery disease, cerebrovascular disease and atrial fibrillation than COVID-19 patients without stroke. 

The analysis also identified Black patients bear a disproportionate share of the COVID-19 ischemic stroke and TIA burden. Black patients accounted for about 25% of the COVID-19 population in the registry but 30.6% of stroke patients. 

“We are seeing the multiplicative effects of complications during these pandemic times,” Shakil said. “These findings show it is more important than ever that we vaccinate rapidly and, in the interim, continue to use non-pharmacologic interventions to limit the spread of COVID-19.”