AHA/ASA Release New Comprehensive Acute Ischemic Stroke Guideline

A new guideline on the early management of acute ischemic stroke released this week by the American Heart Association/American Stroke Association (AHA/ASA) revamps guidance on prehospital care, use of thrombolysis and thrombectomy, management of blood pressure and glucose, pediatric stroke, and more.

The recommendations incorporate new research that has accumulated since the last full guideline was released in 2018, with an update issued in 2019.

Since then, “there’s been a flourishing of stroke trials and impactful results, things that have changed practice and should change practice more,” Shyam Prabhakaran, MD (University of Chicago Medicine, IL), chair of the writing group, told TCTMD. “That’s the real reason why these are so important—because these are long overdue.”

The comprehensive guidance covers stroke systems of care, management in the prehospital setting, acute evaluation and treatment, and in-hospital supportive care and treatment of acute complications, among other areas. It was published online this week in Stroke and will be presented and discussed next week at the International Stroke Conference in New Orleans, LA.

Impact of Mobile Stroke Units

Speaking to some of the recommendations, Prabhakaran said there is increasing evidence  to support use of mobile stroke units, which are ambulances equipped with CT scanners and teams that are trained to administer IV thrombolysis for eligible patients, to speed care. There is a new class 1 recommendation, based on trials like B_PROUD and BEST-MSU, to use mobile stroke units to transport and manage patients who have suspected acute ischemic stroke and are eligible for thrombolytics to improve functional outcomes.

“There are challenges with supporting that financially and with staffing, but ultimately we have strong evidence that those improve outcomes in stroke patients,” Prabhakaran said, noting that use of these units remains limited in the United States. “We’d love it if this helps policymakers maybe provide more support for mobile stroke units through reimbursement. That, I think, is a real important step towards getting more adoption and cost reduction.”

In the prehospital setting, the recommendations around where patients should be taken initially has been updated as well.

“Given recent evidence, this guideline endorses consideration of the characteristics of the local system of care and direct transport to the closest endovascular thrombectomy-capable hospital in the absence of well-functioning systems with rapid interhospital transfer processes,” the authors write.

Thrombolysis and Thrombectomy Expand

Recommendations around use of IV thrombolysis and mechanical thrombectomy have been updated to refine and expand eligibility. The guidance emphasizes the importance of administering thrombolysis as quickly as possible in eligible patients with disabling defects presenting within 4.5 hours of stroke onset, regardless of NIHSS score and without the need for advanced imaging.

Since the last update, several trials have bolstered tenecteplase as a noninferior alternative to alteplase, and there is now a class 1 recommendation to use either tenecteplase 0.25 mg/kg body weight or alteplase 0.9 mg/kg body weight to improve functional outcomes for patients presenting within 4.5 hours.

The guideline authors note that tenecteplase has some practical advantages over alteplase. “It has a lot more simplicity. It can be given as an injection without an infusion over an hour,” Prabhakaran said. “It makes the lives of our staff easier, and it facilitates rapid transfer if the patient is moving from one facility to another facility because you just push the drug and you get them out of there.”

He noted that “many places have started to shift to tenecteplase because of the ease of use.”

The guideline also contains a new class 2a recommendation, based on trials like EXTEND, stating that IV thrombolysis may be reasonable between 4.5 and 9 hours after stroke onset, or when patients wake up with stroke symptoms, if advanced imaging shows salvageable brain tissue.

Thrombolysis may even be beneficial (class 2b recommendation) when administered 4.5 to 24 hours after stroke onset in certain patients with large-vessel occlusions (LVOs) and salvageable brain tissue who can’t undergo mechanical thrombectomy. Though the TIMELESS trial did not show a benefit of using tenecteplase in this late window, other trials in which few patients underwent mechanical thrombectomy, like HOPE and TRACE-III, did show that thrombolysis in select patients could improve outcomes.

In recent years, trials have also been done that expand the reach of mechanical thrombectomy to many more patients, including select patients with large-core strokes presenting up to 24 hours after symptom onset, Prabhakaran pointed out.

A new class 1 recommendation, for example, advises thrombectomy in patients with acute ischemic stroke caused by LVOs in the anterior circulation who present 6 to 24 hours after symptom onset, are younger than 80 years, have an NIHSS score of 6 or higher, and have an ASPECTS of 3 to 5 without significant mass effect on imaging (based on trials like SELECT2 and ANGEL-ASPECT).

Evidence has emerged, from trials like ATTENTION and BAOCHE, that thrombectomy helps for blockages in the posterior circulation as well. The guideline authors recommend (class 1) that patients with a basilar artery occlusion, an NIHSS score of 10 or higher, and mild ischemic damage who present within 24 hours should undergo thrombectomy to improve functional outcomes and reduce mortality.

There are some restrictions on using thrombectomy in scenarios that remain light on evidence, “and that’s in the medium vessels, the small distal vessels, where we’re not sure that . . . the technologies currently work as well,” Prabhakaran said.

Medical Management and Pediatric Stroke

There have been changes to guidance on medical management in the new guideline as well. For instance, a class III recommendation advises against using IV insulin to achieve a blood glucose level of 80 to 130 mg/dL in patients hospitalized with hyperglycemia, because it hasn’t been shown to improve outcomes and increases the risk of severe hypoglycemia.

And new trial evidence has informed recommendations around blood pressure control after IV thrombolysis and endovascular thrombectomy. There is a class III recommendation against lowering systolic BP to less than 140 mm Hg (versus less than 180 mm Hg) in patients with a stroke of mild to moderate severity who have received IV thrombolysis because intensive BP reduction has not been shown to improve functional outcomes.

In addition, trials like ENCHANTED2/MT and OPTIMAL-BP support another class III recommendation against treating to a BP goal below 140 mm Hg for the first 72 hours after successful recanalization by thrombectomy in patients with an LVO in the anterior circulation due to the potential for harm.

Prabhakaran said another major addition is a first attempt at giving specific guidance around diagnosing and treating stroke in pediatric populations, including recommendations on when thrombolysis and endovascular thrombectomy may be considered. “It’s not definitive because the evidence base is not as strong in pediatric stroke, but I think we took the first steps towards guiding healthcare providers” in thinking about these options, he said.

Remaining Knowledge Gaps

Despite the progress made in several areas in recent years, there are still topics that are ripe for further research, Prabhakaran said. For thrombectomy, there’s a need to better understand the impact when used for blockages in the medium and small vessels, for example. “There will be more trials that focus on that space, because I think we know that technologies will get better and some of the reasons those trials failed in medium- and small-vessel occlusion is that current devices probably can’t produce the same results,” he said.

Another important issue in need of additional studies is the use of advanced imaging to select patients for thrombolytic therapy in extended time windows, which will “give people who are in low-resource parts of the world or low-resource settings in the US the option to give thrombolytics safely to patients who can’t get to a thrombectomy center quickly,” Prabhakaran said.

Stroke in pediatric populations also hasn’t received the same attention as it has in adults and requires more evidence, he said.

Neuroprotection, which has not proven successful up to this point and is not recommended in the current guideline, may get another look, as well. “In the era of reperfusion, where you can actually use it as an adjunctive therapy with successful reperfusion, I think that opens up the opportunity potentially that neuroprotective drugs, either those that have been tried and failed or new ones, would be tested in that sort of paradigm,” Prabhakaran said.

Moving forward, the AHA will be moving toward more active management of the guidelines, with real-time updates, to try to avoid another 7-year lapse between iterations, he specified. “When there’s new science, we need to make sure the guidelines and the recommendations are updated.”

This new guideline was endorsed by the American Association of Neurological Surgeons/Congress of Neurological Surgeons, the Neurocritical Care Society, the Society for Academic Emergency Medicine, the Society of NeuroInterventional Surgery, and the Society of Vascular and Interventional Neurology. In addition, the American Academy of Neurology “affirms the value of this statement as an educational tool for neurologists.”