ARTICLE IN BRIEF
The newly released guidelines from the American Heart Association/American Stroke Association extend the time window for treatment with thrombectomy, recommend against certain diagnostic tests for secondary stroke prevention, and suggest treatment for deep vein thrombosis related to stroke.
LOS ANGELES — “Time is brain” remains an important mantra in the new guidelines for the early management of acute ischemic stroke from the American Heart Association/American Stroke Association released in late January at the International Stroke Conference and published in the January 24 online edition of the journal Stroke. But the updated evidence-based review offers revised recommendations about pre-hospital care; urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies; and in-hospital management.
The guidelines were written by a group appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise, with strict adherence to the American Heart Association conflict of interest policy.
Among the newest recommendations is that mechanical thrombectomy should be attempted for carefully selected patients who have large vessel occlusion in the anterior circulation. between six to 16 hours after the patients exhibiting stroke symptoms were last seen normal. The recommendation was based on the findings of the DEFUSE 3 study, also released at the conference and simultaneously published in the January 24 New England Journal of Medicine.
In DEFUSE 3, stroke patients who missed the window of opportunity for treatment with tPA and were within six to 16 hours of the believed onset of symptoms, showed remarkable recovery, said William J. Powers, MD, professor and chairman of neurology at the University of North Carolina, Chapel Hill, who discussed the guidelines at the conference.
Dr. Powers said the guideline committee had advance knowledge of the DEFUSE 3 results and incorporated those results into the new guidelines – two hours after the DEFUSE 3 results were reported at the conference. [For more detailed findings about DEFUSE, see the story, “In the Clinic-Stroke Thrombectomy Window Extended to 16 Hours” on page 26.]
The criteria for mechanical thrombectomy with a stent retriever includes a pre-stroke modified Rankin Score of zero to one; causative occlusion of the internal carotid artery or middle cerebral artery segment; age 18 or over; a National Institutes of Health Stroke Scale score of six or more; and an Alberta Stroke Program Early CT Score (ASPECTS) of six or greater.
Dr. Powers said that criteria that extends thrombectomy to 24 hours after the last time the patient was seen well was also included in the new guidelines — albeit with a lower recommendation level. Whereas the DEFUSE-3 trial-based recommendation was assigned a Level 1A rating, indicating strong, high-level evidence, the extension to 24 hours, based on findings from the DAWN trial, was rated Level IIa B-R, indicating it was suggested based on moderate quality evidence.
The DAWN trial, published online first in November in the New England Journal of Medicine, found that endovascular thrombectomy performed between six and 24 hours after the known onset of stroke symptoms improved the 90-day disability and functional independence outcomes of patients with a large vessel occlusion who had a mismatch between the size of the infarct and the magnitude of clinical deficits compared to medical therapy alone. [For more about the DAWN trial, see the January 11 Neurology Today article, “In the Clinic-Stroke: Thrombectomy Benefit Found to Extend to 24 Hours for Stroke Patients”: http://bit.ly/NT-DAWN.]
The guideline writers also cautioned that before thrombectomy is attempted, proper imaging is required: computed tomography (CT) perfusion, diffusion weighted magnetic resonance imaging (MRI) or MRI perfusion is recommended to aid in patients' selection for mechanical thrombectomy, according to the guideline, but only when imaging and other eligibility criteria from randomized control trials showing benefit are strictly applied.
The guidelines suggest using tPA if the patient can be treated within 4.5 hours of the onset of stroke symptoms, but even in those cases of early response to stroke, the use of thrombectomy relies on meeting precise criteria.
In the 60 pages of guidelines, Dr. Powers and colleagues generally left most treatment recommendations unchanged since the 2013 guideline. However, a major change was the recommendation to drop multiple tests that were routinely performed in stroke patients as part of secondary prevention.
“We took a very hard look at the cost-benefit of doing diagnostic tests to decide what was the best treatment for patients to prevent them from having another stroke,” said Dr. Powers. “It is often assumed that just doing the tests is valuable in every patient and that is good medical practice. It turns out that is actually not good medical practice.”
He said these tests “are expensive; lead to studies that will provide no information about outcome, and may actually lead to further tests and things that actually adversely affect patient outcome.
“We have made recommendations that diagnostic testing be individualized for each patient, and restricted to answering those questions that will lead to a treatment change that will help the patients improve,” he said.
According to the new guidelines, evidence does not support routine use of these diagnostic tests in patients with acute ischemic stroke for preventing secondary stroke: brain MRI; intracranial CT angiography or magnetic resonance angiography (MRA); prolonged cardiac monitoring (clinical benefit is uncertain); echocardiography; and blood cholesterol if a patient is not on a statin.
This recommendation, in particular, drew some heated discussion among neurologists attending the meeting and in online discussion groups.
Another change in the guidelines applies to prevention of deep vein thrombosis in stroke patients who lie in bed for extended periods. “We very carefully evaluated the information as to what is the best way to prevent this and concluded that intermittent pneumatic compression — basically inflatable balloons that go on your calf and intermittently [inflate and deflate] to squeeze the blood out of the veins in your legs — are the most effective treatment for this,” he said. “We recommend that for all patients with stroke who are lying in bed.”
Dr. Powers noted that previously blood thinners were advocated as the most effective way to prevent deep vein thrombosis. “A very careful review of the available information indicates that this is a two-edged sword,” he said. “It reduces the risk of blood clots in the legs traveling to the lungs but it also increases the risk of bleeding elsewhere in your body, and the overall benefit of this seem to be a wash, and their overall efficacy is really quite uncertain.”
The guideline indicates that the benefit of prophylactic-dose subcutaneous heparin [unfractionated heparin or low molecular weight heparin] in immobile patients with acute ischemic stroke “is not well established.”
Karen L. Furie, MD, professor and chair of neurology at the Warren Alpert Medical School of Brown University, who co-authored an editorial accompanying the new guidelines in Stroke, noted that though the guidelines were reached by consensus after reviewing the literature, there was friction or even controversy around some of the recommendations.
Dr. Furie said the way the new guidelines are written — with less text and more attention to the evidence — “will make it harder to refute if you see the evidence presented – unless you can see something that was missed by the committee.”
“I don't think there will be controversy about the data on mechanical thrombectomy,” she said. “I think everyone agrees with that. These results keep getting better and better,” she said.
Dr. Furie noted that it took many years for hospitals and emergency personnel to ramp up for treatment of early strokes with tPA and while that is better now than the era from 1996 to 2010, “it still is not optimal.”
“I think that thrombectomy is going to take off much more rapidly than intravenous thrombolysis,” she said. “The health care community has shown remarkable energy in trying to redesign processes to address these new findings. I think we are going to see rapid change around this issue.”
She cautioned, however, that thrombectomy will not be the answer for most stroke patients. “Realistically we are only talking about 10 to 20 percent of all stroke patients who are going to have a large vessel occlusion, and only half of that group would have imaging results that would make them eligible for thrombectomy,” she said. “It still leaves a lot that has to be done for people who do not have a large vessel occlusion.”
While the guidelines represent a consensus, they are not without some dissent. “The guideline changes were very controversial and stimulated a lot of unrest among the neurologists,” said James C. Grotta, MD, FAAN, director of stroke research at the Memorial Hermann-Texas Medical Center in Houston and director of the Mobile Stroke Unit Consortium, who attended the conference.
“In particular, the removal of MRI, imaging of intracranial arteries, and cholesterol from routine evaluation of stroke patients is very controversial,” Dr. Grotta told Neurology Today. “Also, the strict requirement for advanced imaging before thrombectomy was debatable.”
He also was critical of the guidelines' failure to mention other tools for treatment of stroke. “There are areas with some evidence behind them that were not included,” he said.
“In my own area, the use of mobile stroke units, while still level 2 or 3 evidence, were not even mentioned, while other things with no greater evidence were included.”